In Brazil, the campos rupestres occur over the Brazilian shield, and are characterized by acidic nutrient‐impoverished soils, which are particularly low in phosphorus (P). Despite recognition of the ...campos rupestres as a global biodiversity hotspot, little is known about the diversity of P‐acquisition strategies and other aspects of plant mineral nutrition in this region. To explore nutrient‐acquisition strategies and assess aspects of plant P nutrition, we measured leaf P and nitrogen (N) concentrations, characterized root morphology and determined the percentage arbuscular mycorrhizal (AM) colonization of 50 dominant species in six communities, representing a gradient of soil P availability. Leaf manganese (Mn) concentration was measured as a proxy for carboxylate‐releasing strategies. Communities on the most P‐impoverished soils had the highest proportion of nonmycorrhizal (NM) species, the lowest percentage of mycorrhizal colonization, and the greatest diversity of root specializations. The large spectrum of leaf P concentration and variation in root morphologies show high functional diversity for nutritional strategies. Higher leaf Mn concentrations were observed in NM compared with AM species, indicating that carboxylate‐releasing P‐mobilizing strategies are likely to be present in NM species. The soils of the campos rupestres are similar to the most P‐impoverished soils in the world. The prevalence of NM strategies indicates a strong global functional convergence in plant mineral nutrition strategies among severely P‐impoverished ecosystems.
Incidents of viral outbreaks have increased at an alarming rate over the past decades. The most recent human coronavirus known as COVID-19 (SARS-CoV-2) has already spread around the world and shown R
...values from 2.2 to 2.68. However, the ratio between mortality and number of infections seems to be lower in this case in comparison to other human coronaviruses (such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)). These outbreaks have tested the limits of healthcare systems and have posed serious questions about management using conventional therapies and diagnostic tools. In this regard, the use of nanotechnology offers new opportunities for the development of novel strategies in terms of prevention, diagnosis and treatment of COVID-19 and other viral infections. In this review, we discuss the use of nanotechnology for COVID-19 virus management by the development of nano-based materials, such as disinfectants, personal protective equipment, diagnostic systems and nanocarrier systems, for treatments and vaccine development, as well as the challenges and drawbacks that need addressing.
Innovations in synthetic chemistry have enabled the discovery of many breakthrough therapies that have improved human health over the past century. In the face of increasing challenges in the ...pharmaceutical sector, continued innovation in chemistry is required to drive the discovery of the next wave of medicines. Novel synthetic methods not only unlock access to previously unattainable chemical matter, but also inspire new concepts as to how we design and build chemical matter. We identify some of the most important recent advances in synthetic chemistry as well as opportunities at the interface with partner disciplines that are poised to transform the practice of drug discovery and development.
Enzyme-catalyzed reactions have begun to transform pharmaceutical manufacturing, offering levels of selectivity and tunability that can dramatically improve chemical synthesis. Combining enzymatic ...reactions into multistep biocatalytic cascades brings additional benefits. Cascades avoid the waste generated by purification of intermediates. They also allow reactions to be linked together to overcome an unfavorable equilibrium or avoid the accumulation of unstable or inhibitory intermediates. We report an in vitro biocatalytic cascade synthesis of the investigational HIV treatment islatravir. Five enzymes were engineered through directed evolution to act on non-natural substrates. These were combined with four auxiliary enzymes to construct islatravir from simple building blocks in a three-step biocatalytic cascade. The overall synthesis requires fewer than half the number of steps of the previously reported routes.
Activation of nuclear factor E2-related factor-2 (Nrf2), a sensor of oxidative stress, is neuroprotective in animal models of cerebral ischemia, traumatic brain injury, subarachnoid hemorrhage, and ...spinal cord injury. We show here that Nrf2 activation with sulforaphane (SFN) in vivo or in vitro increases expression and transport activity of three ATP-driven drug efflux pumps at the blood-brain barrier P-glycoprotein, ATP binding cassette b1 (Abcb1); multidrug resistance-associated protein-2 (Mrp2), Abcc2; and breast cancer resistance protein (Bcrp), Abcg2. Dosing rats with SFN increased protein expression of all three transporters in brain capillaries and decreased by 50% brain accumulation of the P-glycoprotein substrate verapamil. Exposing rat or mouse brain capillaries to SFN increased P-glycoprotein, Bcrp, and Mrp2 transport activity and protein expression; SFN increased P-glycoprotein activity in mouse spinal cord capillaries. Inhibiting transcription or translation abolished upregulation of P-glycoprotein activity. No such effects were seen in brain capillaries from Nrf2-null mice, indicating Nrf2 dependence. Nrf2 signaled indirectly to increase transporter activity/expression. The p53 inhibitor pifithrin abolished the SFN-induced increase in transporter activity/expression, and the p53-activator nutlin-3 increased P-glycoprotein activity. SFN did not alter P-glycoprotein transport activity in brain and spinal cord capillaries from p53-null mice. Inhibitors of p38 MAPK and nuclear factor κB (NF-κB) blocked the effects of SFN and nutlin-3 on P-glycoprotein activity. These results implicate Nrf2, p53, and NF-κB in the upregulation of P-glycoprotein, Bcrp, and Mrp2 at blood-CNS barriers. They imply that the barriers are tightened selectively (efflux transporter upregulation) by oxidative stress, providing increased neuroprotection, but also reduced penetration of many therapeutic drugs.
The role of epistasis in evolutionary rescue Freitas, Osmar; Campos, Paulo R. A.
The European physical journal. E, Soft matter and biological physics,
07/2024, Letnik:
47, Številka:
7
Journal Article
Recenzirano
The process by which adaptive evolution preserves a population threatened with extinction due to environmental changes is known as evolutionary rescue. Several factors determine the fate of those ...populations, including demography and genetic factors, such as standing genetic variation, gene flow, availability of
de novo mutations
, and so on. Despite the extensive debate about evolutionary rescue in the current literature, a study about the role of epistasis and the topography of the fitness landscape on the fate of dwindling populations is missing. In the current work, we aim to fill this gap and study the influence of epistasis on the probability of extinction of populations. We present simulation results, and analytical approximations are derived. Counterintuitively, we show that the likelihood of extinction is smaller when the degree of epistasis is higher. The reason underneath is twofold: first, higher epistasis can promote mutations of more significant phenotypic effects, but also, the incongruence between the maps genotype–phenotype and phenotype–fitness turns the fitness landscape at low epistasis more rugged, thus curbing some of its advantages.
Graphic abstract
Diabetes mellitus, an incurable metabolic disease, is characterized by changes in the homeostasis of blood sugar levels, being the subcutaneous injection of insulin the first line treatment. This ...administration route is however associated with limited patient's compliance, due to the risk of pain, discomfort and local infection. Nanoparticles have been proposed as insulin carriers to make possible the administration of the peptide via friendlier pathways without the need of injection, i.e., via oral or nasal routes. Nanoparticles stand for particles in the nanometer range that can be obtained from different materials (e.g., polysaccharides, synthetic polymers, lipid) and are commonly used with the aim to improve the physicochemical stability of the loaded drug and thereby its bioavailability. This review discusses the use of different types of nanoparticles (e.g., polymeric and lipid nanoparticles, liposomes, dendrimers, niosomes, micelles, nanoemulsions and also drug nanosuspensions) for improved delivery of different oral hypoglycemic agents in comparison to conventional therapies.
Microbes broadly constitute several organisms like viruses, protozoa, bacteria, and fungi present in our biosphere. Fast-paced environmental changes have influenced contact of human populations with ...newly identified microbes resulting in diseases that can spread quickly. These microbes can cause infections like HIV, SARS-CoV2, malaria, nosocomial Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), or Candida infection for which there are no available vaccines/drugs or are less efficient to prevent or treat these infections. In the pursuit to find potential safe agents for therapy of microbial infections, natural biflavonoids like amentoflavone, tetrahydroamentoflavone, ginkgetin, bilobetin, morelloflavone, agathisflavone, hinokiflavone, Garcinia biflavones 1 (GB1), Garcinia biflavones 2 (GB2), robustaflavone, strychnobiflavone, ochnaflavone, dulcisbiflavonoid C, tetramethoxy-6,6″-bigenkwanin and other derivatives isolated from several species of plants can provide effective starting points and become a source of future drugs. These biflavonoids show activity against influenza, severe acute respiratory syndrome (SARS), dengue, HIV-AIDS, coxsackieviral, hepatitis, HSV, Epstein-Barr virus (EBV), protozoal (Leishmaniasis, Malaria) infections, bacterial and fungal infections. Some of the biflavonoids can provide antiviral and protozoal activity by inhibition of neuraminidase, chymotrypsin-like protease, DV-NS5 RNA dependant RNA polymerase, reverse transcriptase (RT), fatty acid synthase, DNA polymerase, UL54 gene expression, Epstein−Barr virus early antigen activation, recombinant cysteine protease type 2.8 (r-CPB2.8), Plasmodium falciparum enoyl-acyl carrier protein (ACP) reductase or cause depolarization of parasitic mitochondrial membranes. They may also provide anti-inflammatory therapeutic activity against the infection-induced cytokine storm. Considering the varied bioactivity of these biflavonoids against these organisms, their structure-activity relationships are derived and wherever possible compared with monoflavones. Overall, this review aims to highlight these natural biflavonoids and briefly discuss their sources, reported mechanism of action, pharmacological uses, and comment on resistance mechanism, flavopiridol repurposing and the bioavailability aspects to provide a starting point for anti-microbial research in this area.
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•Natural biflavonoids like amentoflavone, ginkgetin, morelloflavone, agathisflavone, hinokiflavone, robustaflavone, and many others are known.•These biflavonoids have activity against Influenza, SARS, Dengue, HIV, HBV, HSV, EBV, protozoal (Leishmania, Malaria), bacterial and fungal infections.•Structurally these dimeric flavonoids have more effectiveness over the monomeric flavonoids.•Natural biflavonoids have the potential to undergo medicinal chemistry manipulation and become source of new anti-microbial drugs.
•Electro–thermal modular model of PV cells and BPDs depicted by an equivalent circuit.•A thermal equation that yields the BPD junction temperature, including heat transfer.•Comparison of several MPPT ...algorithms, using our model, operating under PS conditions.
As the popularity of solar panels increases, significant research is being performed on maximizing the power extracted from photovoltaic systems. A phenomenon known as partial shading is a major source of power losses for photovoltaic plants. One way to reduce the effects of partial shading conditions is by using bypass–diodes. Typically any number of series and parallel–connected photovoltaic cells, known as photovoltaic cell arrays, are connected in anti–parallel with bypass–diodes. Due to this, it is advantageous to have an equivalent model for a photovoltaic cell array that is connected to bypass–diodes. In order to accurately develop this model, it is necessary to consider both series and parallel configurations of bypass–diodes, as well as the thermal behavior of bypass–diodes. The bypass–diode’s temperature model must be comprised of the constantly changing dissipated power, the effects of wind speed and the ambient temperature. This paper constructs an electro–thermal modular model for any size photovoltaic system and includes the effects of both the photovoltaic cells and bypass–diodes. A detailed analysis of the proposed model is performed and is then validated in both PSCAD/EMTDC and Matlab–Simscape. The proposed model is then further validated by the use of real measurements of ambient temperature, cell temperature, wind speed and then finally by a performance analysis of several maximum–power–point–tracking algorithms.
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