Mechanical interactions between collagen and proteoglycans: implications for the stability of lung tissue.

Collagen and elastin are thought to dominate the elasticity of the connective tissue including lung parenchyma. The glycosaminoglycans on the proteoglycans may also play a role because osmolarity of interstitial fluid can alter the repulsive forces on the negatively charged glycosaminoglycans, allowing them to collapse or inflate, which can affect the stretching and folding pattern of the fibers. Hence, we hypothesized that the elasticity of lung tissue arises primarily from 1) the topology of the collagen-elastin network and 2) the mechanical interaction between proteoglycans and fibers. We measured the quasi-static, uniaxial stress-strain curves of lung tissue sheets in hypotonic, normal, and hypertonic solutions. We found that the stress-strain curve was sensitive to osmolarity, but this sensitivity decreased after proteoglycan digestion. Images of immunofluorescently labeled collagen networks showed that the fibers follow the alveolar walls that form a hexagonal-like structure. Despite the large heterogeneity, the aspect ratio of the hexagons at 30% uniaxial strain increased linearly with osmolarity. We developed a two-dimensional hexagonal network model of the alveolar structure incorporating the mechanical properties of the collagen-elastin fibers and their interaction with proteoglycans. The model accounted for the stress-strain curves observed under all experimental conditions. The model also predicted how aspect ratio changed with osmolarity and strain, which allowed us to estimate the Young's modulus of a single alveolar wall and a collagen fiber. We therefore identify a novel and important role for the proteoglycans: they stabilize the collagen-elastin network of connective tissues and contribute to lung elasticity and alveolar stability at low to medium lung volumes.     

Antifungal effects of the flavonoids kaempferol and quercetin: a possible alternative for the control of fungal biofilms

This study aimed to determine the minimum inhibitory concentration (MIC) of kaempferol and quercetin against planktonic and biofilm forms of the Candida parapsilosis complex. Initially, nine C. parapsilosis sensu stricto, nine C. orthopsilosis and nine C. metapsilosis strains were used. Planktonic susceptibility to kaempferol and quercetin was assessed. Growing and mature biofilms were then exposed to the flavonoids at MIC or 10xMIC, respectively, and theywere also analyzed by confocal laser scanning microscopy. The MIC ranges were 32-128 µg ml^?1 for kaempferol and 0.5-16 µg ml^?1 for quercetin. Kaempferol and quercetin decreased (P?<?0.05) the metabolic activity and biomass of growing biofilms of the C. parapsilosis complex. As for mature biofilms, the metabolic effects of the flavonoids varied, according to the cryptic species, but kaempferol caused an overall reduction in biofilm biomass. Microscopic analyses showed restructuring of biofilms after flavonoid exposure. These results highlight the potential use of these compounds as sustainable resources for the control of fungal biofilms.     

Fasting protects against the side effects of irinotecan but preserves its anti-tumor effect in Apc15lox mutant mice

Irinotecan is a widely used topoisomerase-I-inhibitor with a very narrow therapeutic window because of its severe toxicity. In the current study we have examined the effects of fasting prior to irinotecan treatment on toxicity and anti-tumor activity. FabplCre;Apc^15lox/+ mice, which spontaneously develop intestinal tumors, of 27 weeks of age were randomized into 3-day fasted and ad libitum fed groups, followed by treatment with a flat-fixed high dose of irinotecan or vehicle. Side-effects were recorded until 11 days after the start of the experiment. Tumor size, and markers for cell-cycle activity, proliferation, angiogenesis, and senescence were measured. Fasted mice were protected against the side-effects of irinotecan treatment. Ad libitum fed mice developed visible signs of discomfort including weight loss, lower activity, ruffled coat, hunched-back posture, diarrhea, and leukopenia. Irinotecan reduced tumor size in fasted and ad libitum fed groups similarly compared to untreated controls (2.4 ± 0.67 mm and 2.4 ± 0.82 mm versus 3.0 ± 1.05 mm and 2.8 ± 1.08 mm respectively, P < 0.001). Immunohistochemical analysis showed reduced proliferation, a reduced number of vascular endothelial cells, and increased levels of senescence in tumors of both irinotecan treated groups. In conclusion, 3 days of fasting protects against the toxic side-effects of irinotecan in a clinically relevant mouse model of spontaneously developing colorectal cancer without affecting its anti-tumor activity. These results support fasting as a powerful way to improve treatment of colorectal carcinoma patients.     

Critical role for the kinesin KIF3A in the HIV life cycle in primary human macrophages

Macrophages are long-lived target cells for HIV infection and are considered viral reservoirs. HIV assembly in macrophages occurs in virus-containing compartments (VCCs) in which virions accumulate and are stored. The regulation of the trafficking and release of these VCCs remains unknown. Using high resolution light and electron microscopy of HIV-1–infected primary human macrophages, we show that the spatial distribution of VCCs depended on the microtubule network and that VCC-limiting membrane was closely associated with KIF3A+ microtubules. Silencing KIF3A strongly decreased virus release from HIV-1–infected macrophages, leading to VCC accumulation intracellularly. Time-lapse microscopy further suggested that VCCs and associated KIF3A move together along microtubules. Importantly, KIF3A does not play a role in HIV release from T cells that do not possess VCCs. These results reveal that HIV-1 requires the molecular motor KIF3 to complete its cycle in primary macrophages. Targeting this step may lead to novel strategies to eliminate this viral reservoir.     

Purification and biological effects of Araucaria angustifolia (Araucariaceae) seed lectin

This paper describes the purification and characterization of a new N-acetyl-d-glucosamine-specific lectin from Araucaria angustifolia (AaL) seeds (Araucariaceae) and its anti-inflammatory and antibacterial activities. AaL was purified using a combination of affinity chromatography on a chitin column and ion exchange chromatography on Sephacel-DEAE. The pure protein has 8.0kDa (SDS-PAGE) and specifically agglutinates rabbit erythrocytes, effect that was independent of the presence of divalent cations and was inhibited after incubation with glucose and N-acetyl-d-glucosamine. AaL showed antibacterial activity against Gram-negative and Gram-positive strains, shown by scanning electron microscopy. AaL, intravenously injected into rats, showed anti-inflammatory effect, via carbohydrate site interaction, in the models of paw edema and peritonitis. This lectin can be used as a tool for studying bacterial infections and inflammatory processes.     

Salt-induced changes on H<Superscript>+</Superscript>-ATPase activity,sterol and phospholipid content and lipid peroxidation of root plasma membrane from dwarf-cashew (<Emphasis Type="Italic">Anacardium occidentale</Emphasis> L.) seedlings

The effects of NaCl stress on the growth, water relation, gas exchange, tissue mineral content, and on H⁺-ATPase activity, lipid composition and peroxidation of root plasma membrane-enriched fractions of two genotypes (CCP06 and BRS189, sensitive and tolerant to salt stress, respectively) of dwarf-precocious cashew were studied. Growth reduction was higher in CCP06 than in BRS189. Net photosynthesis decreased in both genotypes, CCP06 being more affected. Roots of BRS189 accumulated higher amount of Na⁺ than those of CCP06 at both salt treatments, whereas Cl⁻ increase was higher only at 8 dS m⁻¹. NaCl at 8 dS m⁻¹ did not modify the plasma membrane H⁺-ATPase activity in CCP06 roots, but significantly increased it in BRS189 roots. Lipid peroxidation was lower in BRS189 than in CCP06 roots. Salinity induced higher accumulation of proline in BRS189 roots. Total phospholipids and free sterols content increased significantly in root plasma membrane of CCP06. However, in BRS189, a slight reduction of free sterols content and no changes in total phospholipids content were observed. Thus, the results suggest that the ability of cashew seedlings to adapt to salt stress is, at least in part, dependent upon the maintenance of integrity and protection against oxidative damage of plasma membrane, which could favor the activation of plasma membrane H⁺-ATPase, as a cellular mechanism to regulate ion exclusion from the shoot.     

MIDAS: software for analysis and visualisation of interallelic disequilibrium between multiallelic markers

Background  

Various software tools are available for the display of pairwise linkage disequilibrium across multiple single nucleotide polymorphisms. The HapMap project also presents these graphics within their website. However, these approaches are limited in their use of data from multiallelic markers and provide limited information in a graphical form.     

When are buttresses and stilt roots necessary for a tree in terra-firme Amazonian forests?

Determinants of the occurrence of buttress and stilt roots are still poorly understood. These may be linked to individual's properties as a way to increase stability as trees get higher, to environmental factors that increase falling risks or interactions of both. We took advantage of a large dataset (presence of buttress, stilt roots, and tree diameter in 8415 trees from 35 1-ha plots in central Amazonia) to investigate how tree and environmental properties interact to determine the occurrence of support structures. We also made detailed measurements of allometry and canopy size in 67 trees of two dominant species. The probability of occurrence of support structures was modeled with multiple logistic regressions and boosted regression trees. We established a best-fitting subset model based on AIC ranking using unsupervised model selection. At the landscape scale, support structures were more common in large trees (b_std = 0.88, p < .001) and valleys (b_std = −0.09, p < .01), due to species turnover along topography and also due to intraspecific variation in the development of buttresses within species, linked to interactions of tree size and topography. The relationship between height and diameter (Height:Diameter) was the most important determinant of buttress occurrence (b_std = −1.57, p < .001). We conclude that less stable soils select a higher frequency of trees with support structures. However, coordinated allometric relationships among stem and crown sizes also influence the need of support structures. Thus, the presence of support structures depends on the interplay of individual plant's allometry and environmentally imposed conditions of instability. Abstract in Portuguese is available with online material.     

Water scarcity in Brazil: part 1—regionalization of the AWARE model characterization factors

The International Journal of Life Cycle Assessment - This paper presents the regionalized water scarcity characterization factors (CFs) of the available water remaining (AWARE) model, which was...