In vitro response to Candida albicans in cultures of whole human blood from young and aged donors

Invasive infections with opportunistic fungi, such as Candida albicans, have become an increasing problem in aged adults in recent years. This work investigates the influence of human ageing on C. albicans recognition by toll-like receptors (TLRs), essential components of the innate immune system, using a cohort of 96 young (15-42 years) and aged (>70 years) human volunteers. No significant differences between aged and young donors were observed on (1) cell surface TLR2, TLR6 and TLR4 expression on lymphocytes, monocytes and granulocytes, (2) production of cytokines [IL-8, IL-1beta, IL-6, IL-10, tumour necrosis factor (TNF)-alpha and IL-12p70] and prostaglandin E(2) (PGE(2)) by whole human blood in response to C. albicans and (3) fungicidal activity of whole blood. A statistically significant higher titre of natural anti-C. albicans antibodies was found in plasma of volunteers between 80 and 95 years old when compared with other age groups, probably as a consequence of the increased levels of serum Ig that has been described in elderly subjects. Therefore, the results indicate that the increased susceptibility to C. albicans infections in the elderly is not a consequence of defects in TLRs expression or signalling, nor of an impaired fungicidal activity of blood.     

Cellular organization of adult neurogenesis in the Common Marmoset

Adult neurogenesis within the subgranular zone (SGZ) of the hippocampal dentate gyrus and the subventricular zone (SVZ) of the lateral ventricle (LV) has been most intensely studied within the brains of rodents such as mice and rats. However, little is known about the cell types and processes involved in adult neurogenesis within primates such as the common marmoset (Callithrix jacchus). Moreover, substantial differences seem to exist between the neurogenic niche of the LV between rodents and humans. Here, we set out to use immunohistochemical and autogradiographic analysis to characterize the anatomy of the neurogenic niches and the expression of cell type-specific markers in those niches in the adult common marmoset brain. Moreover, we demonstrate significant differences in the activity of neurogenesis in the adult marmoset brain compared to the adult mouse brain. Finally, we provide evidence for ongoing proliferation of neuroblasts within both the SGZ and SVZ of the adult brain and further show that the age-dependent decline of neurogenesis in the hippocampus is associated with a decrease in neuroblast cells.     

Associations between rotating night shifts, sleep duration, and telomere length in women

Background

Telomere length has been proposed as a marker of aging. However, our knowledge of lifestyle risk factors determining telomere length is limited.

Methods

We evaluated the associations between years of rotating night shifts, self-reported sleep duration, and telomere length in 4,117 female participants from the Nurses'' Health Study. Telomere length in peripheral blood leukocytes was determined by Real-Time PCR assay. Information on rotating night shifts and sleep duration was collected via questionnaires prior to blood collection. We used multivariable linear regression to investigate the associations between rotating night shifts, sleep duration, and telomere length.

Results

Compared with women in the category (9 hours), those in the lowest category of sleep duration (≤6 hours) had a 0.12 unit decrease in z score after adjustment for age, BMI and cigarette smoking (equivalent to 9-year telomere attrition, P for trend  = 0.05). Significant positive association between sleep duration and telomere length was seen among women under age of 50 (P for trend  = 0.004), but not among those over 50 (P for trend  = 0.33) (P for interaction  = 0.005). In addition, we observed that women with a longer history of rotating night shifts tended to have shorter telomere length, but this relation was not statistically significant (P for trend  = 0.36).

Conclusion

We found that sleep duration was positively associated with telomere length among women under 50 years old. Further research is needed to confirm the observed associations.     

Anti-cancer activity of 5-O-alkyl 1,4-imino-1,4-dideoxyribitols

New derivatives of 1,4-dideoxy-1,4-imino-d-ribitol have been prepared and evaluated for their cytotoxicity on solid and haematological malignancies. 1,4-Dideoxy-5-O-[(9Z)-octadec-9-en-1-yl]-1,4-imino-d-ribitol (13, IC₅₀ ∼2 μM) and its C₁₈-analogues (IC₅₀ <10 μM) are cytotoxic toward SKBR3 (breast cancer) cells. 13 also inhibits (IC₅₀ ∼8 μM) growth of JURKAT cells.     

Export,purification, and activities of affinity tagged <Emphasis Type="Italic">Lactobacillus reuteri</Emphasis> levansucrase produced by <Emphasis Type="Italic">Bacillus megaterium</Emphasis>

Fructosyltransferases, like the Lactobacillus reteri levansucrase, are important for the production of new fructosyloligosaccharides. Various His₆- and Strep-tagged variants of this enzyme were recombinantly produced and exported into the growth medium using the Gram-positive bacterium Bacillus megaterium. Nutrient-rich growth medium significantly enhanced levansucrase production and export. The B. megaterium signal peptide of the extracellular esterase LipA mediated better levansucrase export compared to the one of the penicillin amidase Pac. The combination of protein export via the LipA signal peptide with the coexpression of the signal peptidase gene sipM further increased the levansucrase secretion. Fused affinity tags allowed the efficient one-step purification of the recombinant proteins from the growth medium. However, fused peptide tags led to slightly decreased secretion of tested fusion proteins. After upscaling 2 to 3 mg affinity tagged levansucrase per liter culture medium was produced and exported. Up to 1 mg of His₆-tagged and 0.7 mg of Strep-tagged levansucrase per liter were recovered by affinity chromatography. Finally, the purified levansucrase was shown to synthesize new fructosyloligosaccharides from the novel donor substrates d-Gal-Fru, d-Xyl-Fru, d-Man-Fru, and d-Fuc-Fru. R. Biedendieck and R. Beine contributed equally to this work.     

Plant volatiles mediate attraction to host and non-host plant in apple fruit moth, Argyresthia conjugella

Plant volatiles mediate host finding in insect herbivores and lead to host fidelity and habitat‐specific mating, generating premating reproductive isolation and facilitating sympatric divergence. The apple fruit moth, Argyresthia conjugella Zeller (Lepidoptera: Argyresthiidae), is a particularly suitable species to study the cues and behavioural mechanisms leading to colonization of a new host: it recurrently oviposits on the non‐host plant, apple Malus domestica Borkh. (Rosaceae), where the larvae cannot complete their development. The larval host of the apple fruit moth (Lepidoptera, Argyresthiidae), is rowan Sorbus aucuparia L. (Rosaceae). Fruit setting in rowan, however, fluctuates strongly over large areas in Scandinavia. Every 2–4 years, when too few rowanberries are available for egg laying in forests, apple fruit moth females oviposit instead on apple in nearby orchards, but not on other fruits, such as pear or plum. This poses the question of which cues mediate attraction to rowan and apple, and how apple fruit moth discriminates rowan from apple. Chemical analysis and antennal recordings showed that 11 out of 15 rowan volatiles eliciting an antennal response in A. conjugella females co‐occur in rowan and apple headspace, in a different proportion. In the field, A. conjugella was attracted to several of these plant volatiles, especially to 2‐phenyl ethanol, methyl salicylate, and decanal. Addition of anethole to 2‐phenyl ethanol had a strong synergistic effect, the 1 : 1 blend is a powerful attractant for A. conjugella males and females. These results confirm that volatiles common to both plants may account for a host switch in A. conjugella from rowan to apple. Some of the most attractive compounds, including 2‐phenyl ethanol, anethole, and decanal, which have been found in several apple cultivars, were not present in the headspace of the apple cultivar, Aroma, which is also susceptible to attack by A. conjugella. This supports the idea that the odour signal from apple is suboptimal for attraction of A. conjugella, but is nonetheless sufficient for attraction, during times when rowan is not available for egg laying.     

Natural cytotoxicity of lymphocytes and monocytes and its augmentation by OK432 in melanoma patients

Summary Lymphocytes and monocytes from the peripheral blood of 30 patients with malignant melanoma were tested for natural cytotoxicity against K562 cells in a 3-h ⁵¹Cr-release assay, and the effects of OK432 (a streptococcal preparation) on the cytotoxicity were examined. The lymphocyte cytotoxicity of melanoma patients was similar to that of normal donors and control patients with benign skin disease. Furthermore, the lymphocyte cytotoxicity of melanoma patients was not correlated to the stage of the disease. Similarly, lysis of K562 cells by monocytes isolated by adherence to autologous serum-coated plastic dishes in melanoma patients was comparable to that of controls and not associated with the stage of the disease. Positive monocyte reactions were recorded in 10 of 30 (33%) melanoma patients, seven of 21 (33%) normal donors and three of 10 (30%) control patients. There was no correlation between lymphocyte cytotoxicity and monocyte cytotoxicity. Overnight treatment of monocytes and lymphocytes with OK432 resulted in an increase in cytotoxicity. Significant augmentation of cytotoxicity by OK432 was observed in 28% of the monocyte samples and 86% of the lymphocyte samples, while partially purified human interferon augmented cytotoxicity in 63% of the monocyte samples and all the lymphocyte samples. These results suggest that neither lymphocyte nor monocyte cytotoxicities are depressed in melanoma patients as compared with normal donors and patients with benign disease and that OK432 has a stronger stimulatory effect on lymphocytes than on monocytes.     

Regulatory effects of synthetic liver X receptor- and peroxisome-proliferator activated receptor agonists on sterol transport pathways in polarized cerebrovascular endothelial cells

The blood-brain barrier contributes to maintain brain cholesterol metabolism and protects this uniquely balanced system from exchange with plasma lipoprotein cholesterol. Brain capillary endothelial cells, representing a physiological barrier to the central nervous system, express apolipoprotein A-I (apoA-I, the major high-density lipoprotein (HDL)-associated apolipoprotein), ATP-binding cassette transporter A1 (ABCA1), and scavenger receptor, class B, type I (SR-BI), proteins that promote cellular cholesterol mobilization. Liver X receptors (LXRs) and peroxisome-proliferator activated receptors (PPARs) are regulators of cholesterol transport, and activation of LXRs and PPARs has potential therapeutic implications for lipid-related neurodegenerative diseases. To clarify the functional impact of LXR/PPAR activation, sterol transport along the: (i) ABCA1/apoA-I and (ii) SR-BI/HDL pathway was investigated in primary, polarized brain capillary endothelial cells, an in vitro model of the blood-brain barrier. Activation of LXR (24(S)OH-cholesterol, TO901317), PPARalpha (bezafibrate, fenofibrate), and PPARgamma (troglitazone, pioglitazone) modulated expression of apoA-I, ABCA1, and SR-BI on mRNA and/or protein levels without compromising transendothelial electrical resistance or tight junction protein expression. LXR-agonists and troglitazone enhanced basolateral-to-apical cholesterol mobilization in the absence of exogenous sterol acceptors. Along with the induction of cell surface-located ABCA1, several agonists enhanced cholesterol mobilization in the presence of exogenous apoA-I, while efflux of 24(S)OH-cholesterol (the major brain cholesterol metabolite) in the presence of exogenous HDL remained unaffected. Summarizing, in cerebrovascular endothelial cells apoA-I, ABCA1, and SR-BI represent drug targets for LXR and PPAR-agonists to interfere with cholesterol homeostasis at the periphery of the central nervous system.     

User−Producer Interaction in Housing Energy Innovations

Von Hippel and colleagues have highlighted the crucial role of users in innovation in different industries and types of products. They describe the innovation process in terms of the distinct domains of knowledge that producers and users possess. Producers have knowledge about technical solutions and users about their needs, the context of use, and their own capabilities as users. Both sets of knowledge are characterized by stickiness: They move relatively freely within their own domain but are difficult to transfer outside of it.
In the case of radical innovations for sustainable consumption, the problem of sticky information is compounded. Both producers and consumers need to reach out of their conventional competencies and search for new solutions. Societal actors, such as government bodies or environmental experts, can show the way to such solutions, but this new knowledge needs to be integrated with the sticky knowledge about everyday practices in production and consumption.
In the present article we attempt to conceptualize the role and interaction of user and producer knowledge with the knowledge of environmental experts in housing energy innovations. We do so by applying the user−producer interaction framework to a case study on the introduction of low-energy housing concepts in Finland. On the basis of this analysis, we draw conclusions on the potential and limitations of today's practices in the field. For example, we suggest that user involvement can help to enhance the acceptance of low-energy solutions but that the methods for involving users need to be adapted to the particular circumstances in each industry.     

Reporting randomised clinical trials of analgesics after traumatic or orthopaedic surgery is inadequate: a systematic review

Background  

Several randomised clinical trials (RCTs) of analgesics in postoperative pain after traumatic or orthopaedic surgery (TOS) have been published, but no studies have assessed the quality of these reports. We aimed to examine the quality of reporting RCTs on analgesics for postoperative pain after TOS.