Synthesis of thiol-functionalized N-acetylmuramyl peptide congeners suitable for their conjugation to target molecules

N-Acetylmuramyl-dipeptide and tripeptide derivatives containing at the C-terminus a masked thiol function, i.e. the S-tert-butylthiocysteamine residue, were synthesized via direct condensation of N-acetylmuramic acid with the peptide moiety using the dicyclohexylcarbodiimide/N-hydroxysuccinimide procedure. Reduction with tributylphosphine in aqueous organic media generates the free thiol function for a selective conjugation of these immunomodulants with target molecules via unsymmetrical disulfide bridging with a second thiol group by the sulfenohydrazide procedure or via thio-ether linkage by the addition to maleimido--or aziridine-derivatives.     

Effect of Zeitgeber Intensity Reduction on a Simulated Dual-Oscillator Human Circadian System: Classical and Dynamic Analysis

The two-oscillator model of human circadian rhythmicity was analyzed when a zeitgeber relative intensity of 1, 0.5, or 0.1 was introduced into the equations. Fourier analysis was compared with dynamic analysis such as attractor reconstruction or Liapunov exponent calculation. After a 50 or 90% reduction in zeitgeber intensity, the dynamics of the system became equivalent and differed significantly from those of a system with maximal zeitgeber intensity. When 10% aleatory noise was added to the data, the analysis was still applicable, and the results obtained were essentially the same as in the absence of noise. Dynamic analysis could thus provide a distinct classification for periodic data, based on the type of analysis.     

Effect of water-miscible aprotic solvents on kyotorphin synthesis catalyzed by immobilized α-chymotrypsin

Summary Immobilized -chymotrypsin was used as catalyst to synthesize a kyotorphin derivative (Bz-Tyr-Arg-OEt) in the presence of five water-miscible aprotic solvents (dimethylsulphoxide, dimethylformamide, acetonitrile, acetone and tetrahydrofurane) at 30 °C. By using a kinetically-controlled approach, the maximum synthetic activity was obtained when Arg-OEt was used as nucleophile donor at a concentration 1.5-times higher than the acyl-acceptor substrate (Bz-Tyr-OEt). The water-miscible aprotic solvents enhanced greatly the synthetic activity proportionally to their hidrophilicity properties adequately measured by the log P parameter. At the optimum solvent concentration for the enzymatic peptide synthesis, both the water activity (Aw) of the media and the water content of the immobilized derivative showed a saturation profile against the log P parameter. As a function of the solvent hydrophilicity, these water parameters were shown as key parameters for the increase in the synthetic activity of the enzyme by the presence of these solvents.     

Seed production of cut-leaved teasel (<Emphasis Type=Italic>Dipsacus laciniatus</Emphasis>) in central Missouri

Cut-leaved teasel is an invasive weed in Missouri that reduces the diversification of native species along roadsides and impairs traffic visibility. Teasel is a biennial and grows as a rosette in the first year and flowers the second year. Reproduction is only by seed. Field studies were conducted in 2004 and 2005 at two locations to assess the seed production of cut-leaved teasel. From a natural stand, fifteen plants were tagged at the onset of flowering. Selected plants included those considered growing in a group and those growing alone; a plant was considered alone when no other plant was adjacent for at least 60 cm. Whenever a seedhead completed flowering, it was covered with a cellophane bag and harvested one month later. Linear regression was used to correlate the weight of seeds from a single seedhead and number of seeds to estimate the total seed production per seedhead. The number of seedheads per plant varied from 3 to 56. On average, plants growing alone had 64% more seedheads per plant than plants occurring in a group. Seed numbers in the primary seedhead ranged from 511 to 1,487. Total seed production per plant ranged from 1,309 to 33,527. Seed production was 61% greater for plants growing alone versus those growing in a group and was more prolific in 2005 than in 2004. In addition, seed production per plant varied between locations for plants growing alone, but seed yield per plant was similar for plants growing in groups. Colonization of teasel in new areas is facilitated by higher seedhead numbers per plant and total seed production compared to reproduction of plants in areas of intraspecific competition.     

Experimental evidence for real-time song frequency shift in response to urban noise in a passerine bird

Research has shown that bird songs are modified in different ways to deal with urban noise and promote signal transmission through noisy environments. Urban noise is composed of low frequencies, thus the observation that songs have a higher minimum frequency in noisy places suggests this is a way of avoiding noise masking. Most studies are correlative and there is as yet little experimental evidence that this is a short-term mechanism owing to individual plasticity. Here we experimentally test if house finches (Carpodacus mexicanus) can modulate the minimum frequency of their songs in response to different noise levels. We exposed singing males to three continuous treatments: low–high–low noise levels. We found a significant increase in minimum frequency from low to high and a decrement from high to low treatments. We also found that this was mostly achieved by modifying the frequency of the same low-frequency syllable types used in the different treatments. When different low-frequency syllables were used, those sung during the noisy condition were longer than the ones sang during the quiet condition. We conclude that house finches modify their songs in several ways in response to urban noise, thus providing evidence of a short-term acoustic adaptation.     

Lack of adequate seed supply is a major bottleneck for effective ecosystem restoration in Chile: friendly amendment to Bannister et al. (2018)

We argue that the need for a quality seed supply chain is a major bottleneck for the restoration of Chile's native ecosystems, thus supplementing the list of bottlenecks proposed by Bannister et al. in 2018. Specifically, there is a need for defining seed transfer zones, developing standards and capacities for properly collecting and storing seeds, reducing information gaps on seed physiology and longevity, and implementing an efficient seed supply chain with certification of seed origin and quality. Without such capacities, countries are unlikely to meet their restoration commitments. Although we focus on bottlenecks in Chile, the issues we raise are relevant to other countries and thus the global agenda for ecological restoration.     

Integrin-linked kinase (ILK) modulates wound healing through regulation of hepatocyte growth factor (HGF)

Integrin-linked kinase (ILK) is an intracellular effector of cell–matrix interactions and regulates many cellular processes, including growth, proliferation, survival, differentiation, migration, invasion and angiogenesis. The present work analyzes the role of ILK in wound healing in adult animals using a conditional knock-out of the ILK gene generated with the tamoxifen-inducible Cre-lox system (CRE-LOX mice). Results show that ILK deficiency leads to retarded wound closure in skin. Intracellular mechanisms involved in this process were analyzed in cultured mouse embryonic fibroblast (MEF) isolated from CRE-LOX mice and revealed that wounding promotes rapid activation of phosphatidylinositol 3-kinase (PI3K) and ILK. Knockdown of ILK resulted in a retarded wound closure due to a decrease in cellular proliferation and loss of HGF protein expression during the healing process, in vitro and in vivo. Alterations in cell proliferation and wound closure in ILK-deficient MEF or mice could be rescued by exogenous administration of human HGF. These data demonstrate, for the first time, that the activation of PI3K and ILK after skin wounding are critical for HGF-dependent tissue repair and wound healing.     

Arsenic,Cadmium and Lead Erythrocyte Concentrations in Men with a High,Moderate and Low Level of Physical Training

Biological Trace Element Research - The aim of the present study was to determine changes occurring in the erythrocyte concentrations of arsenic (As), cadmium (Cd) and lead (Pb) in highly trained...     

Exogenous HIV-1 Nef upsets the IFN-γ-induced impairment of human intestinal epithelial integrity

Background

The mucosal tissues play a central role in the transmission of HIV-1 infection as well as in the pathogenesis of AIDS. Despite several clinical studies reported intestinal dysfunction during HIV infection, the mechanisms underlying HIV-induced impairments of mucosal epithelial barrier are still unclear. It has been postulated that HIV-1 alters enterocytic function and HIV-1 proteins have been detected in several cell types of the intestinal mucosa. In the present study, we analyzed the effect of the accessory HIV-1 Nef protein on human epithelial cell line.

Methodology/Principal Findings

We used unstimulated or IFN-γ-stimulated Caco-2 cells, as a model for homeostatic and inflamed gastrointestinal tracts, respectively. We investigated the effect of exogenous recombinant Nef on monolayer integrity analyzing its uptake, transepithelial electrical resistance, permeability to FITC-dextran and the expression of tight junction proteins. Moreover, we measured the induction of proinflammatory mediators. Exogenous Nef was taken up by Caco-2 cells, increased intestinal epithelial permeability and upset the IFN-γ-induced reduction of transepitelial resistance, interfering with tight junction protein expression. Moreover, Nef inhibited IFN-γ-induced apoptosis and up-regulated TNF-α, IL-6 and MIP-3α production by Caco-2 cells while down-regulated IL-10 production. The simultaneous exposure of Caco-2 cells to Nef and IFN-γ did not affect cytokine secretion respect to untreated cells. Finally, we found that Nef counteracted the IFN-γ induced arachidonic acid cascade.

Conclusion/Significance

Our findings suggest that exogenous Nef, perturbing the IFN-γ-induced impairment of intestinal epithelial cells, could prolong cell survival, thus allowing for accumulation of viral particles. Our results may improve the understanding of AIDS pathogenesis, supporting the discovery of new therapeutic interventions.