Urease (urea amidohydrolase, EC 3.5.1.5) is a nickel-containing enzyme produced by plants, fungi, and bacteria that catalyzes the hydrolysis of urea into ammonia and carbamate. Urease is of historical importance in Biochemistry as it was the first enzyme ever to be crystallized (1926). Finding nickel in urease's active site (1975) was the first indication of a biological role for this metal. In this review, historical and structural features, kinetics aspects, activation of the metallocenter and inhibitors of the urea hydrolyzing activity of ureases are discussed. The review also deals with the non-enzymatic biological properties, whose discovery 40 years ago started a new chapter in the study of ureases. Well recognized as virulence factors due to the production of ammonia and alkalinization in diseases by urease-positive microorganisms, ureases have pro-inflammatory, endocytosis-inducing and neurotoxic activities that do not require ureolysis. Particularly relevant in plants, ureases exert insecticidal and fungitoxic effects. Data on the jack bean urease and on jaburetox, a recombinant urease-derived peptide, have indicated that interactions with cell membrane lipids may be the basis of the non-enzymatic biological properties of ureases. Altogether, with this review we wanted to invite the readers to take a second look at ureases, very versatile proteins that happen also to catalyze the breakdown of urea into ammonia and carbamate.

In this work we compared two plant ureases, jackbean urease (JBU) and embryo‐specific soybean urease (SBU) and a bacterial (Bacillus pasteurii) urease, for kinetic parameters and other biological properties described recently for ureases that are independent of the ureolytic activity. The insecticidal effect of ureases was investigated in feeding trials with the cotton sucker bug, Dysdercus peruvianus (Hemiptera) as an insect model. Contrasting with B. pasteurii urease (PBU), both plant ureases presented potent insecticidal activity, with LD₅₀ values of 0.017% (w/w) and 0.052% (w/w) for JBU and SBU, respectively. The insecticidal property of JBU or SBU was not affected by treatment with p‐hydroxymercuribenzoate, an irreversible inhibitor of ureolytic activity of both proteins. Also, contrasting with canatoxin – a urease isoform from jackbean seeds that displays a toxic effect in mice (LD₅₀ = 2 mg·kg⁻¹) – no lethality was seen in mice injected intraperitoneally with JBU or SBU (20 mg·kg⁻¹). Similarly to canatoxin, the three enzymes promoted aggregation of blood platelets (EC₅₀ = 400.0 µg·mL⁻¹, 22.2 µg·mL⁻¹, 15.8 µg·mL⁻¹ for BPU, SBU and JBU, respectively). This platelet activating property was also independent of urease activity. Comparison of the kinetic properties indicated that SBU is fivefold less susceptible than JBU to inhibition by acetohydroxamic acid, a chelator of Ni⁺² and Zn⁺² ions. The ureases also showed different susceptibility to agents that modify cysteine residues, such as p‐hydroxymercuribenzoate and p‐benzoquinone. Altogether, these data emphasize that biological properties that are independent of ureolytic activity are not restricted to jackbean ureases and that these proteins may have a role in plant defense against insect predators.

This study aimed to critically review the literature available regarding the Zika virus outbreak in Brazil and its possible association with microcephaly cases. Experts from Instituto do Cérebro do Rio Grande do Sul performed a critical (nonsystematic) literature review regarding different aspects of the Zika virus outbreak in Brazil, such as transmission, epidemiology, diagnostic criteria, and its possible association with the increase of microcephaly reports. The PubMed search using the key word "Zika virus" in February 2016 yielded 151 articles. The manuscripts were reviewed, as well as all publications/guidelines from the Brazilian Ministry of Health, World Health Organization and Centers for Disease Control and Prevention (CDC - United States). Epidemiological data suggest a temporal association between the increased number of microcephaly notifications in Brazil and outbreak of Zika virus, primarily in the Brazil's Northeast. It has been previously documented that many different viruses might cause congenital acquired microcephaly. Still there is no consensus on the best curve to measure cephalic circumference, specifically in preterm neonates. Conflicting opinions regarding the diagnosis of microcephaly (below 2 or 3 standard deviations) that should be used for the notifications were also found in the literature. The development of diagnostic techniques that confirm a cause-effect association and studies regarding the physiopathology of the central nervous system impairment should be prioritized. It is also necessary to strictly define the criteria for the diagnosis of microcephaly to identify cases that should undergo an etiological investigation.

Canatoxin is a toxic protein isolated from the jackbean, Canavalia ensiformis. The toxin injected intraperitoneally is lethal for mice and rats; however, it is inactive if given orally. In this study. Manduca sexta (L.) (Lepidoptera), Schistocerca Americana (Drury) (Orthoptera), Drosophila melanogester (L.) (Diptera), Aedes aegypti (L.) (Diptera), Rhodnius prolixus (Stål)(Hemiptera), and Callosobruchus maculatus (F.) (Coleoptera) were fed on canatoxin- containing diets. No effects were seen in M. sexta, S. Americana, D. melanogaster or A. aegypti. No traces of canatoxin were found in their feces, suggesting that the protein was digested completely by these insects, which characteristically have a trypsin-based digestion. In contrast, canatoxin was lethal for insects displaying cathepsin-based digestion. Thus, for C. maculatus, a diet containing 0.25% wt:wt canatoxin caused complete inhibition of larval growth. When R. prolixus were fed on canatoxin, 2 effects were seen: impairment of water excretion and increased lethality 48-96 h after feeding. The lethal effect of canatoxin in R. prolixus was blocked partially or completely when the digestion of the toxin by R. prolixus midgut enzymes was impaired. The data showed that canatoxin is highly toxic when ingested by some species of insects but not affecting others, probably in correlation with the characteristics of the digestive process of the insect.