Determination of the processes driving the acquisition of immunity to malaria using a mathematical transmission model

Acquisition of partially protective immunity is a dominant feature of the epidemiology of malaria among exposed individuals. The processes that determine the acquisition of immunity to clinical disease and to asymptomatic carriage of malaria parasites are poorly understood, in part because of a lack of validated immunological markers of protection. Using mathematical models, we seek to better understand the processes that determine observed epidemiological patterns. We have developed an age-structured mathematical model of malaria transmission in which acquired immunity can act in three ways (“immunity functions”): reducing the probability of clinical disease, speeding the clearance of parasites, and increasing tolerance to subpatent infections. Each immunity function was allowed to vary in efficacy depending on both age and malaria transmission intensity. The results were compared to age patterns of parasite prevalence and clinical disease in endemic settings in northeastern Tanzania and The Gambia. Two types of immune function were required to reproduce the epidemiological age-prevalence curves seen in the empirical data; a form of clinical immunity that reduces susceptibility to clinical disease and develops with age and exposure (with half-life of the order of five years or more) and a form of anti-parasite immunity which results in more rapid clearance of parasitaemia, is acquired later in life and is longer lasting (half-life of >20 y). The development of anti-parasite immunity better reproduced observed epidemiological patterns if it was dominated by age-dependent physiological processes rather than by the magnitude of exposure (provided some exposure occurs). Tolerance to subpatent infections was not required to explain the empirical data. The model comprising immunity to clinical disease which develops early in life and is exposure-dependent, and anti-parasite immunity which develops later in life and is not dependent on the magnitude of exposure, appears to best reproduce the pattern of parasite prevalence and clinical disease by age in different malaria transmission settings. Understanding the effector mechanisms underlying these two immune functions will assist in the design of transmission-reducing interventions against malaria.     

Enzymes that hydrolyze adenine nucleotides of patients with hypercholesterolemia and inflammatory processes

The activity of NTPDase (EC 3.6.1.5, apyrase, CD39) was verified in platelets from patients with increasing cholesterol levels. A possible association between cholesterol levels and inflammatory markers, such as oxidized low-density lipoprotein, highly sensitive C-reactive protein and oxidized low-density lipoprotein autoantibodies, was also investigated. Lipid peroxidation was estimated by measurement of thiobarbituric acid reactive substances in serum. The following groups were studied: group I, < 150 mg.dL(-1) cholesterol; group II, 151-200 mg.dL(-1) cholesterol; group III, 201-250 mg.dL(-1) cholesterol; and group IV, > 251 mg.dL(-1) cholesterol. The results demonstrated that both ATP hydrolysis and ADP hydrolysis were enhanced as a function of cholesterol level. Low-density lipoprotein levels increased concomitantly with total cholesterol levels. Triglyceride levels were increased in the groups with total cholesterol above 251 mg.dL(-1). Oxidized low-density lipoprotein levels were elevated in groups II, III, and IV. Highly sensitive C-reactive protein was elevated in the group with cholesterol levels higher than 251 mg.dL(-1). Oxidized low-density lipoprotein autoantibodies were elevated in groups III and IV. Thiobarbituric acid reactive substance content was enhanced as a function of cholesterol level. In summary, hypercholesterolemia is associated with enhancement of inflammatory response, oxidative stress, and ATP and ADP hydrolysis. The increased ATP and ADP hydrolysis in group IV was confirmed by an increase in CD39 expression on its surface. The increase in CD39 activity is possibly related to a compensatory response to the inflammatory and pro-oxidative state associated with hypercholesterolemia.     

Attenuation of cardiac mitochondrial dysfunction by melatonin in septic mice

The existence of an inducible mitochondrial nitric oxide synthase has been recently related to the nitrosative/oxidative damage and mitochondrial dysfunction that occurs during endotoxemia. Melatonin inhibits both inducible nitric oxide synthase and inducible mitochondrial nitric oxide synthase activities, a finding related to the antiseptic properties of the indoleamine. Hence, we examined the changes in inducible nitric oxide synthase/inducible mitochondrial nitric oxide synthase expression and activity, bioenergetics and oxidative stress in heart mitochondria following cecal ligation and puncture-induced sepsis in wild-type (iNOS(+/+)) and inducible nitric oxide synthase-deficient (iNOS(-/-)) mice. We also evaluated whether melatonin reduces the expression of inducible nitric oxide synthase/inducible mitochondrial nitric oxide synthase, and whether this inhibition improves mitochondrial function in this experimental paradigm. The results show that cecal ligation and puncture induced an increase of inducible mitochondrial nitric oxide synthase in iNOS(+/+) mice that was accompanied by oxidative stress, respiratory chain impairment, and reduced ATP production, although the ATPase activity remained unchanged. Real-time PCR analysis showed that induction of inducible nitric oxide synthase during sepsis was related to the increase of inducible mitochondrial nitric oxide synthase activity, as both inducible nitric oxide synthase and inducible mitochondrial nitric oxide synthase were absent in iNOS(-/-) mice. The induction of inducible mitochondrial nitric oxide synthase was associated with mitochondrial dysfunction, because heart mitochondria from iNOS(-/-) mice were unaffected during sepsis. Melatonin treatment blunted sepsis-induced inducible nitric oxide synthase/inducible mitochondrial nitric oxide synthase isoforms, prevented the impairment of mitochondrial homeostasis under sepsis, and restored ATP production. These properties of melatonin should be considered in clinical sepsis.     

The importance of polymerization and galloylation for the antiproliferative properties of procyanidin-rich natural extracts

Grape (Vitis vinifera) and pine (Pinus pinaster) bark extracts are widely used as nutritional supplements. Procyanidin-rich fractions from grape and pine bark extract showing different mean degrees of polymerization, percentage of galloylation (percentage of gallate esters) and reactive oxygen species-scavenging capacity were tested on HT29 human colon cancer cells. We observed that the most efficient fractions in inhibiting cell proliferation, arresting the cell cycle in G(2) phase and inducing apoptosis were the grape fractions with the highest percentage of galloylation and mean degree of polymerization. Additionally, the antiproliferative effects of grape fractions were consistent with their oxygen radical-scavenging capacity and their ability to trigger DNA condensation-fragmentation.     

Nod factor-independent ‘crack-entry’ symbiosis in dalbergoid legume Arachis hypogaea

Dalbergoids are typified by crack-entry symbiosis which is evidenced to be Nod Factor (NF)-independent in several Aeschynomene legumes. Natural symbionts of the dalbergoid legume Arachis hypogaea are always NF-producing, prompting us to check whether symbiosis in this legume could also be NF-independent. For this, we followed the symbiosis with two NF-containing bradyrhizobial strains – SEMIA6144, a natural symbiont of Arachis and ORS285, a versatile nodulator of Aeschynomene legumes, along with their corresponding nodulation (nod) mutants. Additionally, we investigated NF-deficient bradyrhizobia like BTAi1, a natural symbiont of Aeschynomene indica and the WBOS strains that were natural endophytes of Oryza sativa, collected from an Arachis-Oryza intercropped field. While SEMIA6144ΔnodC was non-nodulating, both ORS285 and ORS285ΔnodB could induce functional nodulation, although with lower efficiency than SEMIA6144. On the other hand, all the NF-deficient strains – BTAi1, WBOS2 and WBOS4 showed comparable nodulation with ORS285 indicating Arachis to harbour an NF-independent mechanism of symbiosis. Intriguingly, symbiosis in Arachis, irrespective of whether it was NF-dependent or independent, was always associated with the curling or branching of the rosette root hairs at the lateral root bases. Thus, despite being predominantly described as an NF-dependent legume, Arachis does retain a vestigial, less-efficient form of NF-independent symbiosis.     

A Water-absorbent Mat Incorporating β-cyclodextrin/eugenol Inclusion Complex for Preservation of Cold Fresh Mutton

To extend the shelf life of cold fresh mutton, the water-absorbent antibacterial mat was developed. This mat was composed of polylactic acid-β-cyclodextrin/eugenol (PLA-β-CD/EUG) fiber membrane, super absorbent polymer (SAP) and filter paper, in which the fiber membrane was developed by the electrospinning technique. The β-CD/EUG inclusion complexes were shown to form successfully by scanning electron microscope (SEM), fourier transform infrared spectroscopy (FTIR), water contact angle (WCA) analysis. The release experiment indicated that the PLA-β-CD/EUG fiber membranes had a slow-release effect, especially in the fatty food simulant. The water-absorbent antibacterial mats can restrain the growth of six spoilage bacteria. The mats were evaluated for the preservation of cold fresh mutton. The results revealed that it displayed prolongation of shelf life upon 8 days during the mutton at 4 °C storage period. The water-absorbent antibacterial mat can slowly release natural antibacterial agents and absorb water to achieve preservation, suggesting a potential application in meat products.

     

Edible zombis: fresh fish and the industry of cosmetic corpses

Doing research on fishery commodities in Portugal led us to an enigma: for a dead fish to be fresco (fresh) it must be alive. This paradox manifests at a popular, commercial, and legal level. It denotes the interruption of the difference between being dead and being alive in the commodity form. In Portugal, we suggest, the commercialization of peixe fresco (fresh fish) is based on the production and consumption of edible ‘zombis’: seafood corpses technologically and symbolically crafted as undead. An open concept, ‘edible zombis’ is part of an experimental vocabulary that foregrounds the productive agency of undeadness, both biological and commercial, in the seafood economic complex. It relates to the ordinary practice of necromancy in the commodity-based world. Edible zombis are commodity fetishes that fetishize their producers and consumers, suspending them from the capitalist system in which they live.     

Genetic strategies for improving hyaluronic acid production in recombinant bacterial culture

Hyaluronic acid (HA) is a biopolymer of repeating units of glucuronic acid and N-acetylglucosamine. Its market was valued at USD 8.9 billion in 2019. Traditionally, HA has been obtained from rooster comb-like animal tissues and fermentative cultures of attenuated pathogenic streptococci. Various attempts have been made to engineer a safe micro-organism for HA synthesis; however, the HA titres obtained from these attempts are in general still lower than those achieved by natural, pathogenic producers. In this scenario, ways to increase HA molecule length and titres in already constructed strains are gaining attention in the last years, but no recent publication has reviewed the main genetic strategies applied to improve HA production on heterologous hosts. In light of that, we hereby compile the advances made in the engineering of micro-organisms to improve HA synthesis.     

Global distribution of plasmid-mediated colistin resistance mcr gene in Salmonella: A systematic review

This systematic review focuses on obtaining the most relevant information from multiple studies that detected a mobilized colistin resistance mcr gene in Salmonella for a better comprehension of its global distribution. A group of strategic and systematic keywords were combined to retrieve research data on the detection frequency of the mcr gene globally from four database platforms (Google Scholar, Science Direct, PubMed and Scielo). Forty-eight studies attended all the eligibility criteria and were selected. China was the country with the highest frequency of Salmonella strains with the mcr gene, and Europe exhibited a wide diversity of countries with positive mcr strains. In addition, animals and humans carried the highest frequency of positive strains for the mcr gene. Salmonella Typhimurium was the most frequent serovar carrying the mcr gene. Apparently, colistin overuse in animal husbandry has increased the selective pressure of antimicrobial resistance, resulting in the emergence of a plasmid-mediated colistin resistance mcr gene in China. The mcr-positive Salmonella strains are recently predominant worldwide, which is probably due to the capacity of this gene to be swiftly horizontally transmissible. The transmission ability of mcr-positive Salmonella strains to humans through the consumption of contaminated animal-based food is a public health concern.     

Long-term changes in temperate marine fish assemblages are driven by a small subset of species

The species composition of plant and animal assemblages across the globe has changed substantially over the past century. How do the dynamics of individual species cause this change? We classified species into seven unique categories of temporal dynamics based on the ordered sequence of presences and absences that each species contributes to an assemblage time series. We applied this framework to 14,434 species trajectories comprising 280 assemblages of temperate marine fishes surveyed annually for 20 or more years. Although 90% of the assemblages diverged in species composition from the baseline year, this compositional change was largely driven by only 8% of the species' trajectories. Quantifying the reorganization of assemblages based on species shared temporal dynamics should facilitate the task of monitoring and restoring biodiversity. We suggest ways in which our framework could provide informative measures of compositional change, as well as leverage future research on pattern and process in ecological systems.