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Phosphorylation is an essential process in biological events and is considered critical for biological functions. In tissues, protein phosphorylation mainly occurs on tyrosine (Tyr), serine (Ser) and threonine (Thr) residues. The balance between phosphorylation and dephosphorylation is under the control of two super enzyme families, protein kinases (PKs) and protein phosphatases (PPs), respectively. Although there are many selective and effective drugs targeting phosphokinases, developing drugs targeting phosphatases is challenging. PTP1B, one of the most central protein tyrosine phosphatases (PTPs), is a key player in several human diseases and disorders, such as diabetes, obesity, and hematopoietic malignancies, through modulation of different signaling pathways. However, due to high conservation among PTPs, most PTP1B inhibitors lack specificity, raising the need to develop new strategies targeting this enzyme. In this mini-review, we summarize three classes of PTP1B inhibitors with different mechanisms: (1) targeting multiple aryl-phosphorylation sites including the catalytic site of PTP1B; (2) targeting allosteric sites of PTP1B; (3) targeting specific mRNA sequence of PTP1B. All three types of PTP1B inhibitors present good specificity over other PTPs and are promising for the development of efficient small molecules targeting this enzyme.

Understanding and forecasting current and future consequences of coastal warming require a fine-scale assessment of the near-shore temperature changes. Here we show that despite the fact that 71% of the world's coastlines are significantly warming, rates of change have been highly heterogeneous both spatially and seasonally. We demonstrate that 46% of the coastlines have experienced a significant decrease in the frequency of extremely cold events, while extremely hot days are becoming more common in 38% of the area. Also, we show that the onset of the warm season is significantly advancing earlier in the year in 36% of the temperate coastal regions. More importantly, it is now possible to analyse local patterns within the global context, which is useful for a broad array of scientific fields, policy makers and general public. A detailed assessment of near-shore temperature changes is needed for improved forecasts of the consequences of coastal warming. Here, changes in coastal sea surface temperature are estimated, showing that although 71% of the world's coastlines are warming, the rates of change have varied spatially.

U2 small nuclear RNA auxiliary factor 1 (U2AF1) is a multifunctional protein that plays a crucial role in the regulation of RNA splicing during eukaryotic gene expression. U2AF1 belongs to the SR family of splicing factors and is involved in the removal of introns from mRNAs and exon-exon binding. Mutations in U2AF1 are frequently observed in myelodysplastic syndrome, primary myelofibrosis, chronic myelomonocytic leukaemia, hairy cell leukaemia and other solid tumours, particularly in lung, pancreatic, and ovarian carcinomas. Therefore, targeting U2AF1 for therapeutic interventions may be a viable strategy for treating malignant diseases. In the present review, the pathogenic mechanisms associated with U2AF1 in different malignant diseases were summarized, and the potential of related targeting agents was discussed. Additionally, the feasibility of natural product-based therapies directed against U2AF1 was explored.

Natural populations of widely distributed organisms often exhibit genetic clinal variation over their geographical ranges. The European anchovy, Engraulis encrasicolus, illustrates this by displaying a two-clade mitochondrial structure clinally arranged along the eastern Atlantic. One clade has low frequencies at higher latitudes, whereas the other has an anti-tropical distribution, with frequencies decreasing towards the tropics. The distribution pattern of these clades has been explained as a consequence of secondary contact after an ancient geographical isolation. However, it is not unlikely that selection acts on mitochondria whose genes are involved in relevant oxidative phosphorylation processes. In this study, we performed selection tests on a fragment of 1044 bp of the mitochondrial cytochrome b gene using 455 individuals from 18 locations. We also tested correlations of six environmental features: temperature, salinity, apparent oxygen utilization and nutrient concentrations of phosphate, nitrate and silicate, on a compilation of mitochondrial clade frequencies from 66 sampling sites comprising 2776 specimens from previously published studies. Positive selection in a single codon was detected predominantly (99%) in the anti-tropical clade and temperature was the most relevant environmental predictor, contributing with 59% of the variance in the geographical distribution of clade frequencies. These findings strongly suggest that temperature is shaping the contemporary distribution of mitochondrial DNA clade frequencies in the European anchovy.

Ideally, antineoplastic treatment aims to selectively eradicate cancer cells without causing systemic toxicity. A great number of antineoplastic agents (AAs) are available nowadays, with well-defined therapeutic protocols. The poor bioavailability, non-selective action, high systemic toxicity, and lack of effectiveness of most AAs have stimulated the search for novel chemotherapy protocols, including technological approaches that provide drug delivery systems (DDS) for gold standard medicines. Nanostructured lipid carriers (NLC) are DDS that contain a core of solid and lipid liquids stabilised by surfactants. NLC have high upload capacity for lipophilic drugs, such as the majority of AAs. These nanoparticles can be prepared with a diversity of biocompatible (synthetic or natural) lipid blends, administered by different routes and functionalised for targeting purposes. This review focused on the research carried out from 2000 to now, regarding NLC formulations for AAs (antimetabolites, antimitotics, alkylating agents, and antibiotics) encapsulation, with special emphasis on studies carried out in vivo. NLC systems for codelivery of AAs were also considered, as well as those for non-classical drugs and therapies (natural products and photosensitisers). NLC have emerged as powerful DDS to improve the bioavailability, targeting and efficacy of antineoplastics, while decreasing their toxic effect in the treatment of different types of cancer.

Diabetes mellitus is one of the most common todays public health problems. According to a survey by the World Health Organization, this metabolic disorder has reached global epidemic proportions, with a worldwide prevalence of 8.5% in the adult population. The present study aimed to investigate the hypoglycemic effect of aqueous extract of Mangifera indica (EAMI) leaves in streptozotocin-induced diabetic rats. Sixty male rats were divided into 2 groups: Normoglycemic and Diabetic. Each group was subdivided into negative control, glibenclamide 3 or 10 mg/kg, EAMI 125, 250, 500, and 1000 mg/kg. Intraperitoneal injection of streptozotocin 100 mg/kg was used to DM induction. The hypoglycemic response was assessed acutely after two and four weeks of treatment. After a 6-hour fasting period, the fasting blood glucose of animals was verified, and 2.5 g/kg glucose solution was orally administered. The insulin tolerance test and plasma insulin levels assessment were performed in the morning after fasting of 12 to 14 hours. The chemical analysis of EAMI showed high levels of phenolic compounds. There was no significant difference in fasting blood glucose between normoglycemic and diabetic groups, and that EAMI did not have an acute effect on diabetes. After two and four weeks of treatment, the extract significantly reduced blood glucose levels, exceeding glibenclamide effects. EAMI was effective in maintaining the long-term hypoglycemic effect, as well as, significantly increased the sensitivity of diabetic animals to insulin and the plasma insulin level.

Measuring cardiac frequency provides a non‐invasive approach to quantifying sublethal stress responses of invertebrates to environmental stressors, such as heat stress. Existing cardiac monitoring methods rely on limited‐performance hardware, and data processing is still largely manual or semi‐automated. This makes current approaches cumbersome, restricting the complexity and scalability of experiments that can be done. To address these challenges, we developed a fully automated toolkit that integrates hardware, firmware and a new R package ‘heartbeatr’ to streamline the collection and analysis of large volumes of cardiac data. We assessed heartbeatr's automated frequency detection against a curated database of 78,769 manually assessed heartbeats, demonstrating high reliability. We provide recommendations for conducting long‐term, high‐throughput cardiac monitoring in ecological research.

Understanding the effects of climate-mediated environmental variation on the distribution of organisms is critically important in an era of global change. We used wavelet analysis to quantify the spatiotemporal (co)variation in daily water temperature for predicting the distribution of cryptic refugia across 16 intertidal sites that were characterized as ‘no’, ‘weak’ or ‘strong’ upwelling and spanned 2000 km of the European Atlantic Coast. Sites experiencing weak upwelling exhibited high synchrony in temperature but low levels of co-variability at monthly to weekly timescales, whereas the opposite was true for sites experiencing strong upwelling. This suggests upwelling generates temporal thermal refugia that can promote organismal performance by both supplying colder water that mitigates thermal stress during hot Summer months and ensuring high levels of fine-scale variation in temperature that reduce the duration of thermal extremes. Additionally, pairwise correlograms based on the Pearson-product moment correlation coefficient and wavelet coherence revealed scale dependent trends in temperature fluctuations across space, with a rapid decay in strong upwelling sites at monthly and weekly timescales. This suggests upwelling also generates spatial thermal refugia that can ‘rescue’ populations from unfavorable conditions at local and regional scales. Overall, this study highlights the importance of identifying cryptic spatiotemporal refugia that emerge from fine-scale environmental variation to map potential patterns of organismal performance in a rapidly changing world.

Different combinations of behavioural and physiological responses may play a crucial role in the ecological success of species, notably in the context of biological invasions. The invasive mussel Xenostrobus securis has successfully colonised the inner part of the Galician Rias Baixas (NW Spain), where it co-occurs with the commercially-important mussel Mytilus galloprovincialis. This study investigated the effect of a heatwave on the physiological and behavioural responses in monospecific or mixed aggregations of these species. In a mesocosm experiment, mussels were exposed to simulated tidal cycles and similar temperature conditions to those experienced in the field during a heat-wave that occurred in the summer of 2013, when field robo-mussels registered temperatures up to 44.5°C at low tide. The overall responses to stress differed markedly between the two species. In monospecific aggregations M. galloprovincialis was more vulnerable than X. securis to heat exposure during emersion. However, in mixed aggregations, the presence of the invader was associated with lower mortality in M. galloprovincialis. The greater sensitivity of M. galloprovincialis to heat exposure was reflected in a higher mortality level, greater induction of Hsp70 protein and higher rates of respiration and gaping activity, which were accompanied by a lower heart rate (bradycardia). The findings show that the invader enhanced the physiological performance of M. galloprovincialis, highlighting the importance of species interactions in regulating responses to environmental stress. Understanding the complex interactions between ecological factors and physiological and behavioural responses of closely-related species is essential for predicting the impacts of invasions in the context of future climate change.

Background: Coronavirus Disease 2019 (COVID-19) became the deadliest pandemic of the new millennium. One year after it became a pandemic, the current COVID-19 situation in Brazil is an example of how the impacts of a pandemic are beyond health outcomes and how health, social, and political actions are intertwined.Objectives: We aimed to provide an overview of the first year of the COVID-19 pandemic in Brazil, from a social and political point of view, and to discuss the perspectives from now on.Methods: This is a narrative review using official, scientific (PubMed, Medline, and SciELO databases) and publicly available data. Press articles were also used that contain important information not found in these databases.Findings: We address the impacts of COVID-19 in different regions of Brazil, on indigenous populations, health care workers, and how internal social contrasts impacted the pandemic’s advance across the country. We also discuss key points that culminated in the country’s failed management of the COVID-19 spread, such as poor management of the public health care system, disparities between public and private health care infrastructure, lack of mass testing and viral spread tracking, lack of preparedness and planning to implement strict isolation and social distancing measures, and, most importantly, political instability, a deteriorating Health Ministry and sabotaging attitudes of the country’s president, including anti-scientific actions, underplaying COVID-19 severity, spreading and powering fake news about the pandemic, promoting knowingly inefficient medications for COVID-19 treatment, and interference in collective health policies, including the country’s vaccination plan.Conclusions:After one year of COVID-19 and a disastrous management of the disease, Brazil has more than 11 million cases, 270,000 deaths, and the highest number of daily deaths due to COVID-19 in the world, most of which could have been avoided and can be credited to negligence of municipal, state, and federal authorities, especially President Jair Messias Bolsonaro. Unfortunately, the country is an example of what not to do in a pandemic setting.Key Points:* One year after COVID-19 was declared a pandemic, Brazil had the second higher number of cases and deaths, and the highest number of daily deaths due to the disease.* Lack of massive testing, non-stringent and ineffective collective health policies, poor management of the public health care system, and political instability were the main drivers of the country’s flawed management of the COVID-19 advancement.* Anti-science and sabotaging actions by government had a pivotal role in the country’s current situation.* Brazil has a large territory and is marked by social contrasts among different regions and states, which showed contrasting data regarding the impact caused by COVID-19.* COVID-19 databases and data sharing are important to provide an overview of epidemiological aspects of the disease; however, Brazil lacks standardization in these datasets.