Epidemiology and Outcome of Fungemia in a Cancer Cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031)

In a prospective cohort study of 145 030 admissions of cancer patients from 13 European Organisation for Research and Treatment of Cancer centers fungemia occurred in 0.23%. Candida albicans was the predominant pathogen. Fungemia was associated with substantial mortality. Antifungal prophylaxis and remission of cancer predicted better surviva

Growth of c-oriented MgB2 thin films by Pulsed Laser Deposition: structural characterization and electronic anisotropy

MgB2 thin films were deposited using Pulsed Laser Deposition (PLD) and ex-situ annealing in Mg atmosphere. The films presented critical temperatures up to 36K and turned out to be preferentially c-oriented both on Al2O3 (r-cut) and MgO(100) substrates. Synchrotron analyses gave also some indications of in plane texturing. The films exhibit very fine grain size (1200angstromin the basal plane and 100angstrom along c-axis) but the general resistivity behavior and the remarkable extension of the irreversible region confirm that the grains boundaries are not barriers for supercurrents. Upper critical field measurements with the magnetic field perpendicular and parallel with respect to the film surface evidenced a field anisotropy ratio of 1.8. The Hc2 values are considerably higher with respect to the bulk ones, namely when the field lies in the basal plane, and the field-temperature phase diagram for the two magnetic field orientations suggest the possibility of strongly enhancing the pinning region by means of texturing.Comment: 20 pages, 6 figure

Advanced material against human (Including Covid‐19) and plant viruses: nanoparticles as a feasible strategy

The SARS‐CoV‐2 virus outbreak revealed that these nano‐pathogens have the ability to rapidly change lives. Undoubtedly, SARS‐CoV‐2 as well as other viruses can cause important global impacts, affecting public health, as well as, socioeconomic development. But viruses are not only a public health concern, they are also a problem in agriculture. The current treatments are often ineffective, are prone to develop resistance, or cause considerable adverse side effects. The use of nanotechnology has played an important role to combat viral diseases. In this review three main aspects are in focus: first, the potential use of nanoparticles as carriers for drug delivery. Second, its use for treatments of some human viral diseases, and third, its application as antivirals in plants. With these three themes, the aim is to give to readers an overview of the progress in this promising area of biotechnology during the 2017–2020 period, and to provide a glance at how tangible is the effectiveness of nanotechnology against viruses. Future prospects are also discussed. It is hoped that this review can be a contribution to general knowledge for both specialized and non‐specialized readers, allowing a better knowledge of this interesting topic.REDES‐ANID. Grant Number: 180003 Universidad de La Frontera. Grant Number: DI20‐1003 FAPESP. Grant Numbers: 2018/08194‐2, 2018/02832‐7 CNPq. Grant Numbers: 404815/2018‐9, 313117/2019‐5 CONICYT/FAPESP. Grant Number: 2018/08194‐2 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Grant Numbers: 001, ANID/FONDAP/15130015 FCT. Grant Number: PTDC/CTM‐TEX/28295/2017 FEDER POCI Portugal 2020 program COMPETE. Grant Number: UID/CTM/00264/2019 FCT/MCTE

Role of Toll-Like Receptor (TLR) 2 in Experimental Bacillus cereus Endophthalmitis

Bacillus cereus causes a uniquely rapid and blinding intraocular infection, endophthalmitis. B. cereus replicates in the eye, synthesizes numerous toxins, and incites explosive intraocular inflammation. The mechanisms involved in the rapid and explosive intraocular immune response have not been addressed. Because Toll-like receptors (TLRs) are integral to the initial recognition of organisms during infection, we hypothesized that the uniquely explosive immune response observed during B. cereus endophthalmitis is directly influenced by the presence of TLR2, a known Gram-positive pathogen recognition receptor. To address this hypothesis, we compared the courses of experimental B. cereus endophthalmitis in wild type C57BL/6J mice to that of age-matched homozygous TLR2-/- mice. Output parameters included analysis of bacterial growth, inflammatory cell (PMN) infiltration, cytokine/chemokine kinetics, retinal function testing, and histology, with N≥4 eyes/assay/time point/mouse strain. B. cereus grew at similar rates to108 CFU/eye by 12 h, regardless of the mouse strain. Retinal function was preserved to a greater degree in infected TLR2-/- eyes compared to that of infected wild type eyes, but infected eyes of both mouse strains lost significant function. Retinal architecture was preserved in infected TLR2-/- eyes, with limited retinal and vitreal cellular infiltration compared to that of infected wild type eyes. Ocular myeloperoxidase activities corroborated these results. In general, TNFα, IFNγ, IL6, and KC were detected in greater concentrations in infected wild type eyes than in infected TLR2-/- eyes. The absence of TLR2 resulted in decreased intraocular proinflammatory cytokine/chemokine levels and altered recruitment of inflammatory cells into the eye, resulting in less intraocular inflammation and preservation of retinal architecture, and a slightly greater degree of retinal function. These results demonstrate TLR2 is an important component of the initial ocular response to B. cereus endophthalmitis

Overview of the Proton-coupled MCT (SLC16A) Family of Transporters: Characterization, Function and Role in the Transport of the Drug of Abuse γ-Hydroxybutyric Acid

The transport of monocarboxylates, such as lactate and pyruvate, is mediated by the SLC16A family of proton-linked membrane transport proteins known as monocarboxylate transporters (MCTs). Fourteen MCT-related genes have been identified in mammals and of these seven MCTs have been functionally characterized. Despite their sequence homology, only MCT1–4 have been demonstrated to be proton-dependent transporters of monocarboxylic acids. MCT6, MCT8 and MCT10 have been demonstrated to transport diuretics, thyroid hormones and aromatic amino acids, respectively. MCT1–4 vary in their regulation, tissue distribution and substrate/inhibitor specificity with MCT1 being the most extensively characterized isoform. Emerging evidence suggests that in addition to endogenous substrates, MCTs are involved in the transport of pharmaceutical agents, including γ-hydroxybuytrate (GHB), 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins), salicylic acid, and bumetanide. MCTs are expressed in a wide range of tissues including the liver, intestine, kidney and brain, and as such they have the potential to impact a number of processes contributing to the disposition of xenobiotic substrates. GHB has been extensively studied as a pharmaceutical substrate of MCTs; the renal clearance of GHB is dose-dependent with saturation of MCT-mediated reabsorption at high doses. Concomitant administration of GHB and l-lactate to rats results in an approximately two-fold increase in GHB renal clearance suggesting that inhibition of MCT1-mediated reabsorption of GHB may be an effective strategy for increasing renal and total GHB elimination in overdose situations. Further studies are required to more clearly define the role of MCTs on drug disposition and the potential for MCT-mediated detoxification strategies in GHB overdose

Secretory structures in plants: lessons from the Plumbaginaceae on their origin, evolution and roles in stress tolerance

Special IssueThe Plumbaginaceae (non-core Caryophyllales) is a family well known for species adapted to a wide range of arid and saline habitats. Of its salt-tolerant species, at least 45 are in the genus Limonium; two in each of Aegialitis, Limoniastrum and Myriolimon, and one each in Psylliostachys, Armeria, Ceratostigma, Goniolimon and Plumbago. All the halophytic members of the family have salt glands, which are also common in the closely related Tamaricaceae and Frankeniaceae. The halophytic species of the three families can secrete a range of ions (Na+, K+, Ca2+, Mg2+, Cl−, HCO3 −, SO4 2-) and other elements (As, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn). Salt glands are, however, absent in salt-tolerant members of the sister family Polygonaceae. We describe the structure of the salt glands in the three families and consider whether glands might have arisen as a means to avoid the toxicity of Na+ and/or Cl− or to regulate Ca2+ concentrations within the leaves. We conclude that the establishment of lineages with salt glands took place after the split between the Polygonaceae and its sister group the Plumbaginaceaeinfo:eu-repo/semantics/publishedVersio

Obesity-Related Oxidative Stress: the Impact of Physical Activity and Diet Manipulation

Obesity-related oxidative stress, the imbalance between pro-oxidants and antioxidants (e.g., nitric oxide), has been linked to metabolic and cardiovascular disease, including endothelial dysfunction and atherosclerosis. Reactive oxygen species (ROS) are essential for physiological functions including gene expression, cellular growth, infection defense, and modulating endothelial function. However, elevated ROS and/or diminished antioxidant capacity leading to oxidative stress can lead to dysfunction. Physical activity also results in an acute state of oxidative stress. However, it is likely that chronic physical activity provides a stimulus for favorable oxidative adaptations and enhanced physiological performance and physical health, although distinct responses between aerobic and anaerobic activities warrant further investigation. Studies support the benefits of dietary modification as well as exercise interventions in alleviating oxidative stress susceptibility. Since obese individuals tend to demonstrate elevated markers of oxidative stress, the implications for this population are significant. Therefore, in this review our aim is to discuss (i) the role of oxidative stress and inflammation as associated with obesity-related diseases, (ii) the potential concerns and benefits of exercise-mediated oxidative stress, and (iii) the advantageous role of dietary modification, including acute or chronic caloric restriction and vitamin D supplementation

Numt-Mediated Double-Strand Break Repair Mitigates Deletions during Primate Genome Evolution

Non-homologous end joining (NHEJ) is the major mechanism of double-strand break repair (DSBR) in mammalian cells. NHEJ has traditionally been inferred from experimental systems involving induced double strand breaks (DSBs). Whether or not the spectrum of repair events observed in experimental NHEJ reflects the repair of natural breaks by NHEJ during chromosomal evolution is an unresolved issue. In primate phylogeny, nuclear DNA sequences of mitochondrial origin, numts, are inserted into naturally occurring chromosomal breaks via NHEJ. Thus, numt integration sites harbor evidence for the mechanisms that act on the genome over evolutionary timescales. We have identified 35 and 55 lineage-specific numts in the human and chimpanzee genomes, respectively, using the rhesus monkey genome as an outgroup. One hundred and fifty two numt-chromosome fusion points were classified based on their repair patterns. Repair involving microhomology and repair leading to nucleotide additions were detected. These repair patterns are within the experimentally determined spectrum of classical NHEJ, suggesting that information from experimental systems is representative of broader genetic loci and end configurations. However, in incompatible DSBR events, small deletions always occur, whereas in 54% of numt integration events examined, no deletions were detected. Numts show a statistically significant reduction in deletion frequency, even in comparison to DSBR involving filler DNA. Therefore, numts show a unique mechanism of integration via NHEJ. Since the deletion frequency during numt insertion is low, native overhangs of chromosome breaks are preserved, allowing us to determine that 24% of the analyzed breaks are cohesive with overhangs of up to 11 bases. These data represent, to the best of our knowledge, the most comprehensive description of the structure of naturally occurring DSBs. We suggest a model in which the sealing of DSBs by numts, and probably by other filler DNA, prevents nuclear processing of DSBs that could result in deleterious repair