A Two-Antibody Pan-Ebolavirus Cocktail Confers Broad Therapeutic Protection in Ferrets and Nonhuman Primates

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Oxidative stress in primary culture hepatocytes isolated from partially hepatectomized rats

The aim of this study was to evaluate the influence of partial hepatectomy prior to cell isolation on hepatocytes in vitro. We characterized the possible changes of various stress oxidative parameters within the first 24 h after seeding. Male Wistar rats served as donors. Hepatocytes were isolated by collagenase digestion from either liver of simulated surgery (SH) or from liver 1 h after 70% hepatectomy (PH), and the changes in stress parameters were analyzed after 1, 3, 18, and 24 h in culture. At 24 h, only hepatocytes from PH maintained significantly increased reactive oxygen species production, oxidized glutathione percentage, and Cu/Zn superoxide dismutase and catalase activities. Our results show that hepatocytes suffer significant cell injury as a result of the isolation procedure, but primary cultured cells from SH metabolically recover from this stress after 18 h. After this time, primary culture hepatocytes primed by PH maintain their in vivo-like metabolic activities (increase in both oxidative stress and antioxidant status).     

Two stochastic processes shape diverse senescence patterns in a single‐cell organism

Despite advances in aging research, a multitude of aging models, and empirical evidence for diverse senescence patterns, understanding of the biological processes that shape senescence is lacking. We show that senescence of an isogenic Escherichia coli bacterial population results from two stochastic processes. The first process is a random deterioration process within the cell, such as generated by random accumulation of damage. This primary process leads to an exponential increase in mortality early in life followed by a late age mortality plateau. The second process relates to the stochastic asymmetric transmission at cell fission of an unknown factor that influences mortality. This secondary process explains the difference between the classical mortality plateaus detected for young mothers’ offspring and the near nonsenescence of old mothers’ offspring as well as the lack of a mother–offspring correlation in age at death. We observed that lifespan is predominantly determined by underlying stochastic stage dynamics. Surprisingly, our findings support models developed for metazoans that base their arguments on stage‐specific actions of alleles to understand the evolution of senescence. We call for exploration of similar stochastic influences that shape aging patterns beyond simple organisms.     

Anemochory of diapausing stages of microinvertebrates in North American drylands

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Widening the antimicrobial spectrum of esters of bicyclic amines: In vitro effect on gram-positive Streptococcus pneumoniae and gram-negative non-typeable Haemophilus influenzae biofilms

Antibiotic resistance is a global current threat of increasing importance. Moreover, biofilms represent a medical challenge since the inherent antibiotic resistance of their producers demands the use of high doses of antibiotics over prolonged periods. Frequently, these therapeutic measures fail, contributing to bacterial persistence, therefore demanding the development of novel antimicrobials. Esters of bicyclic amines (EBAs), which are strong inhibitors of Streptococcus pneumoniae growth, were initially designed as inhibitors of pneumococcal choline-binding proteins on the basis of their structural analogy to the choline residues in the cell wall. However, instead of mimicking the characteristic cell chaining phenotype caused by exogenously added choline on planktonic cultures of pneumococcal cells, EBAs showed an unexpected lytic activity. In this work we demonstrate that EBAs display a second, and even more important, function as cell membrane destabilizers. We then assayed the inhibitory and disintegrating activity of these molecules on pneumococcal biofilms. The selected compound (EBA 31) produced the highest effect on S. pneumoniae (encapsulated and non-encapsulated) biofilms at very low concentrations. EBA 31 was also effective on mixed biofilms of non-encapsulated S. pneumoniae plus non-typeable Haemophilus influenzae, two pathogens frequently forming a self-produced biofilm in the human nasopharynx. These results support the role of EBAs as a promising alternative for the development of novel, broad-range antimicrobial drugs encompassing both Gram-positive and Gram-negative pathogens.     

Morphological types of Taenia solium cysticerci

In human brain cysticercosis, there are three morphological types of cysticercus. Teresa Robielo, Angelica Rivas and Ana Flisser describe the appearance and possible taxonomic position of these forms, and discuss their relation to the various pathologies of neurocysticercosis.     

Direct inhibition of the hexose transporter GLUT1 by tyrosine kinase inhibitors

The facilitative hexose transporter GLUT1 is a multifunctional protein that transports hexoses and dehydroascorbic acid, the oxidized form of vitamin C, and interacts with several molecules structurally unrelated to the transported substrates. Here we analyzed in detail the interaction of GLUT1 with a group of tyrosine kinase inhibitors that include natural products of the family of flavones and isoflavones and synthetic compounds such as the tyrphostins. These compounds inhibited, in a dose-dependent manner, the transport of hexoses and dehydroascorbic acid in human myeloid HL-60 cells, in transfected Chinese hamster ovary cells overexpressing GLUT1, and in normal human erythrocytes, and blocked the glucose-displaceable binding of cytochalasin B to GLUT1 in erythrocyte ghosts. Kinetic analysis of transport data indicated that only tyrosine kinase inhibitors with specificity for ATP binding sites inhibited the transport activity of GLUT1 in a competitive manner. In contrast, those inhibitors that are competitive with tyrosine but not with ATP failed to inhibit hexose uptake or did so in a noncompetitive manner. These results, together with recent evidence demonstrating that GLUT1 is a nucleotide binding protein, support the concept that the inhibitory effect on transport is related to the direct interaction of the inhibitors with GLUT1. We conclude that predicted nucleotide-binding motifs present in GLUT1 are important for the interaction of the tyrosine kinase inhibitors with the transporter and may participate directly in the binding transport of substrates by GLUT1.     

Ablation of renin-expressing juxtaglomerular cells results in a distinct kidney phenotype

Renin-expressing cells are peculiar in that they act as differentiated cells, producing the hormone renin, while they also seem to act as progenitors for other renal cell types. As such, they may have functions independent of their ability to generate renin/angiotensin. To test this hypothesis, we ablated renin-expressing cells during development by placing diphtheria toxin A chain (DTA) under control of the Ren1d mouse renin promoter by homologous recombination in a two-renin gene strain (Ren2 and Ren1d). Renin-expressing cells are essentially absent from kidneys in homozygotes (DTA/DTA) which, unlike wild-type mice, are unable to recruit renin-expressing cells when homeostasis is threatened. In contrast, renin staining in the submandibular gland (SMG), which expresses mainly Ren2, is normal. Homozygous mice survive normally, but the kidneys are small and have morphological abnormalities: 25% of the glomeruli are hyperplastic or atrophic, tubules are dilated and atrophic, and areas of undifferentiated cells exist near the atrophic glomeruli and tubules. However, in contrast to the very abnormal renal vessels found when renin-angiotensin system genes are deleted, the kidney vessels in homozygotes have normal wall thickness and no decrease in lumen size. Homozygotes have severely reduced kidney and plasma renin concentrations and females have reduced blood pressure. Homozygotes have elevated blood urea nitrogen and potassium levels, which are suggestive of altered renal function. We conclude that renin cells per se are necessary for the morphological integrity of the kidney and may have a role in maintenance of normal kidney function.