Phase Separation Behavior of Caseins in Milk Containing Flaxseed Gum and κ-Carrageenan: A Light-Scattering and Ultrasonic Spectroscopy Study

The physico-chemical properties of skim milk containing κ-carrageenan (in the concentration range 0–0.06% w/v), flaxseed gum (in the concentration range 0–0.40% w/v), or a mixture of both polysaccharides were studied using dynamic light scattering, under diluted conditions, as well as in situ, undiluted, using diffusing wave spectroscopy (DWS) and ultrasonic spectroscopy. Flaxseed gum causes phase separation in milk mixtures, because of thermodynamic incompatibility between the casein micelles and the polysaccharide chains. Confocal microscopy and ultrasonic spectroscopy showed that while the addition of 0.01% κ-carrageenan was not sufficient to hinder phase separation, when 0.03% was added, the helix–helix interactions between κ-carrageenan molecules were sufficient to form a network and stabilize the system. DWS clearly demonstrated that clusters of casein micelles still form even at very low concentrations of polysaccharides (below the visible phase separation threshold) and that κ-carrageenan hinders visible phase separation by decreasing the mobility of the casein micelles.     

Impact of naturalistic lighting on hospitalized stroke patients in a rehabilitation unit: Design and measurement

Introduction and rationale: Stroke is a major cause of acquired cerebral disability among adults, frequently accompanied by depression, anxiety, cognitive impairment, disrupted sleep and fatigue. New ways of intervention to prevent these complications are therefore needed. The major circadian regulator, the suprachiasmatic nucleus, is mainly controlled by natural daylight, and the blue spectrum is considered the most powerful. During stroke rehabilitation, patients typically are mostly indoors and therefore not exposed to the natural daytime variation in light intensity. Furthermore, several rehabilitation hospitals may be exposed to powerful light in the blue spectrum, but at a time that is adversely related to their endogenous circadian phase, for example in the late evening instead of the daytime. Hypothesis: Naturalistic light that mimics the natural daytime spectrum variation will have a positive impact on the health of poststroke patients admitted to rehabilitation. We test specifically for improved sleep and less fatigue (questionnaires, polysomnography, Actiwatch), improved well-being (questionnaires), lessen anxiety and depression (questionnaires), improved cognition (tests), stabilizing of the autonomous nervous system (ECG/HR, blood pressure, temperature) and stabilizing of the diurnal biochemistry (blood markers). Study design: The study is a prospective parallel longitudinal randomized controlled study (quasi randomization). Stroke patients in need of rehabilitation will be included at the acute stroke unit and randomized to either the intervention unit (naturalistic lighting) or the control unit (CU) (standard lighting). The naturalistic light is installed in the entire IU (Cromaviso, Denmark). Conclusion: This study aims to elucidate the influence of naturalistic light on patients during long-term hospitalization in a real hospital setting. The hypotheses are based on preclinical research, as studies using naturalistic light have never been performed before. Investigating the effects of naturalistic light in a clinical setting is therefore much needed.     

Nutritional strategies to modulate inflammation and oxidative stress pathways via activation of the master antioxidant switch Nrf2

The nuclear factor E2-related factor 2 (Nrf2) plays an important role in cellular protection against cancer, renal, pulmonary, cardiovascular and neurodegenerative diseases where oxidative stress and inflammation are common conditions. The Nrf2 regulates the expression of detoxifying enzymes by recognizing the human Antioxidant Response Element (ARE) binding site and it can regulate antioxidant and anti-inflammatory cellular responses, playing an important protective role on the development of the diseases. Studies designed to investigate how effective Nrf2 activators or modulators are need to be initiated. Several recent studies have shown that nutritional compounds can modulate the activation of Nrf2–Keap1 system. This review aims to discuss some of the key nutritional compounds that promote the activation of Nrf2, which may have impact on the human health.     

Design,synthesis and cholinesterase inhibitory properties of new oxazole benzylamine derivatives

Abstract

The enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are primary targets in attenuating the symptoms of neurodegenerative diseases. Their inhibition results in elevated concentrations of the neurotransmitter acetylcholine which supports communication among nerve cells. It was previously shown for trans-4/5-arylethenyloxazole compounds to have moderate AChE and BChE inhibitory properties. A preliminary docking study showed that elongating oxazole molecules and adding a new NH group could make them more prone to bind to the active site of both enzymes. Therefore, new trans-amino-4-/5-arylethenyl-oxazoles were designed and synthesised by the Buchwald-Hartwig amination of a previously synthesised trans-chloro-arylethenyloxazole derivative. Additionally, naphthoxazole benzylamine photoproducts were obtained by efficient photochemical electrocyclization reaction. Novel compounds were tested as inhibitors of both AChE and BChE. All of the compounds exhibited binding preference for BChE over AChE, especially for trans-amino-4-/5-arylethenyl-oxazole derivatives which inhibited BChE potently (IC₅₀ in µM range) and AChE poorly (IC₅₀?100?µM). Therefore, due to the selectivity of all of the tested compounds for binding to BChE, these compounds could be applied for further development of cholinesterase selective inhibitors.

• HIGHLIGHTS

• Series of oxazole benzylamines were designed and synthesised

• The tested compounds showed binding selectivity for BChE

• Naphthoxazoles were more potent AChE inhibitors

     

Persistent versus transient tree encroachment of temperate peat bogs: effects of climate warming and drought events

Peatlands store approximately 30% of global soil carbon, most in moss‐dominated bogs. Future climatic changes, such as changes in precipitation patterns and warming, are expected to affect peat bog vegetation composition and thereby its long‐term carbon sequestration capacity. Theoretical work suggests that an episode of rapid environmental change is more likely to trigger transitions to alternative ecosystem states than a gradual, but equally large, change in conditions. We used a dynamic vegetation model to explore the impacts of drought events and increased temperature on vegetation composition of temperate peat bogs. We analyzed the consequences of six patterns of summer drought events combined with five temperature scenarios to test whether an open peat bog dominated by moss (Sphagnum) could shift to a tree‐dominated state. Unexpectedly, neither a gradual decrease in the amount of summer precipitation nor the occurrence of a number of extremely dry summers in a row could shift the moss‐dominated peat bog permanently into a tree‐dominated peat bog. The increase in tree biomass during drought events was unable to trigger positive feedbacks that keep the ecosystem in a tree‐dominated state after a return to previous ‘normal’ rainfall conditions. In contrast, temperature increases from 1 °C onward already shifted peat bogs into tree‐dominated ecosystems. In our simulations, drought events facilitated tree establishment, but temperature determined how much tree biomass could develop. Our results suggest that under current climatic conditions, peat bog vegetation is rather resilient to drought events, but very sensitive to temperature increases, indicating that future warming is likely to trigger persistent vegetation shifts.     

New structure–activity relationship studies in a series of N,N-bis(cyclohexanol)amine aryl esters as potent reversers of P-glycoprotein-mediated multidrug resistance (MDR)

As a continuation of previous research on a new series of potent and efficacious P-gp-dependent multidrug resistant (MDR) reversers with a N,N-bis(cyclohexanol)amine scaffold, we have designed and synthesized several analogs by modulation of the two aromatic moieties linked through ester functions to the N,N-bis(cyclohexanol)amine, aiming to optimize activity and to extend structure–activity relationships (SAR) within the series. This scaffold, when esterified with two different aromatic carboxylic acids, gives origin to four geometric isomers (cis/trans, trans/trans, cis/cis and trans/cis).The new compounds were tested on doxorubicin-resistant erythroleukemia K562 cells (K562/DOX) in the pirarubicin uptake assay. Most of them resulted in being potent modulators of the extrusion pump P-gp, showing potency values ([I]_0.5) in the submicromolar and nanomolar range. Of these, compounds 2b, 2c, 3d, 5a–d and 6d, showed excellent efficacy with a α_max close to 1. Selected compounds (2d, 3a, 3b, 5a–d) were further studied to evaluate their doxorubicin cytotoxicity potentiation (RF) on doxorubicin-resistant erythroleukemia K562 cells and were found able to enhance significantly doxorubicin cytotoxicity on K562/DOX cells.The results of both pirarubicin uptake and the cytotoxicity assay, indicate that the new compounds of the series are potent P-gp-mediated MDR reversers. They present a structure with a mix of flexible and rigid moieties, a property that seems critical to allow the molecules to choose the most productive of the several binding modes possible in the transporter recognition site.In particular, compounds 5c and 5d, similar to the already reported analogous isomers 1c and 1d,²⁹ are potent and efficacious modulators of P-gp-dependent MDR and may be promising leads for the development of MDR-reversal drugs.     

Mapping the Genes for Susceptibility and Response to Leishmania tropica in Mouse

Background

L. tropica can cause both cutaneous and visceral leishmaniasis in humans. Although the L. tropica-induced cutaneous disease has been long known, its potential to visceralize in humans was recognized only recently. As nothing is known about the genetics of host responses to this infection and their clinical impact, we developed an informative animal model. We described previously that the recombinant congenic strain CcS-16 carrying 12.5% genes from the resistant parental strain STS/A and 87.5% genes from the susceptible strain BALB/c is more susceptible to L. tropica than BALB/c. We used these strains to map and functionally characterize the gene-loci regulating the immune responses and pathology.

Methods

We analyzed genetics of response to L. tropica in infected F₂ hybrids between BALB/c×CcS-16. CcS-16 strain carries STS-derived segments on nine chromosomes. We genotyped these segments in the F₂ hybrid mice and tested their linkage with pathological changes and systemic immune responses.

Principal Findings

We mapped 8 Ltr (Leishmania tropica response) loci. Four loci (Ltr2, Ltr3, Ltr6 and Ltr8) exhibit independent responses to L. tropica, while Ltr1, Ltr4, Ltr5 and Ltr7 were detected only in gene-gene interactions with other Ltr loci. Ltr3 exhibits the recently discovered phenomenon of transgenerational parental effect on parasite numbers in spleen. The most precise mapping (4.07 Mb) was achieved for Ltr1 (chr.2), which controls parasite numbers in lymph nodes. Five Ltr loci co-localize with loci controlling susceptibility to L. major, three are likely L. tropica specific. Individual Ltr loci affect different subsets of responses, exhibit organ specific effects and a separate control of parasite load and organ pathology.

Conclusion

We present the first identification of genetic loci controlling susceptibility to L. tropica. The different combinations of alleles controlling various symptoms of the disease likely co-determine different manifestations of disease induced by the same pathogen in individual mice.     

Allometric Models for Tree Volume and Total Aboveground Biomass in a Tropical Humid Forest in Costa Rica1

Allometric equations for the estimation of tree volume and aboveground biomass in a tropical humid forest were developed based on direct measurements of 19 individuals of seven tree species in Northern Costa Rica. The volume and the biomass of the stems represented about two‐thirds of the total volume and total aboveground biomass, respectively. The average stem volume varied between 4 and 11 Mg/tree and the average total aboveground biomass ranged from 4 to 10 mg/tree. The mean specific gravity of the sampled trees was 0.62 ± 0.06 (g/cm³). The average biomass expansion factor was 1.6 ± 0.2. The best‐fit equations for stem and total volume were of logarithmic form, with diameter at breast height (R²= 0.66 ? 0.81) as an independent variable. The best‐fit equations for total aboveground biomass that were based on combinations of diameter at breast height, and total and commercial height as independent variables had R² values between 0.77 and 0.87. Models recommended for estimating total aboveground biomass are based on diameter at breast height, because the simplicity of these models is advantageous. This variable is easy to measure accurately in the field and is the most common variable recorded in forest inventories. Two widely used models in literature tend to underestimate aboveground biomass in large trees. In contrast, the models developed in this study accurately estimate the total aboveground biomass in these trees.