Unlike fellows – a review of primate–non‐primate associations

Throughout many regions of the tropics, non‐primate animals – mainly birds and mammals – have been observed to follow primate groups and to exploit dropped food and flushed prey. The anecdotal nature of most of the numerous reports on these primate–non‐primate associations (PNPAs) may obscure the biological significance of such associations. We review the existing literature and test predictions concerning the influence of primate traits (body size, activity patterns, dietary strategies, habitat, group size) on the occurrence of PNPAs. Furthermore, we examine the influence of non‐primates' dietary strategies on the occurrence of PNPAs, and the distribution of benefits and costs. We detected a strong signal in the geographic distribution of PNPAs, with a larger number of such associations in the Neotropics compared to Africa and Asia. Madagascar lacks PNPAs altogether. Primate body size, activity patterns, habitat and dietary strategies as well as non‐primate dietary strategies affect the occurrence of PNPAs, while primate group size did not play a role. Benefits are asymmetrically distributed and mainly accrue to non‐primates. They consist of foraging benefits through the consumption of dropped leaves and fruits and flushed prey, and anti‐predation benefits through eavesdropping on primate alarm calls and vigilance. Where quantitative information is available, it has been shown that benefits for non‐primates can be substantial. The majority of PNPAs can thus be categorized as cases of commensalism, while mutualism is very rare. Our review provides evidence that the ecological function of primates extends beyond their manifold interactions with plants, but may remain underestimated.     

Habitat heterogeneity and mammalian predator–prey interactions

• 1 In predator–prey theory, habitat heterogeneity can affect the relationship between kill rates and prey or predator density through its effect on the predator's ability to search for, encounter, kill and consume its prey. Many studies of predator–prey interactions include the effect of spatial heterogeneity, but these are mostly based on species with restricted mobility or conducted in experimental settings.
• 2 Here, we aim to identify the patterns through which spatial heterogeneity affects predator–prey dynamics and to review the literature on the effect of spatial heterogeneity on predator–prey interactions in terrestrial mammalian systems, i.e. in freely moving species with high mobility, in non‐experimental settings. We also review current methodologies that allow the study of the predation process within a spatial context.
• 3 When the functional response includes the effect of spatial heterogeneity, it usually takes the form of predator‐dependent or ratio‐dependent models and has wide applicability.
• 4 The analysis of the predation process through its different stages may further contribute towards identifying the spatial scale of interest and the specific spatial mechanism affecting predator–prey interactions.
• 5 Analyzing the predation process based on the functional response theory, but separating the stages of predation and applying a multiscale approach, is likely to increase our insight into how spatial heterogeneity affects predator–prey dynamics. This may increase our ability to forecast the consequences of landscape transformations on predator–prey dynamics.

     

Sprouted and Freeze‐Dried Wheat and Oat Seeds – Phytochemical Profile and in Vitro Biological Activities

This research was carried out to study phytochemical profile, in vitro antioxidant capacity, reducing power, anti‐hyperglycemic, anti‐inflammatory activities and simulated gastrointestinal digestion of 7‐day old cereal sprouts: spelt wheat ‘Nirvana’ (WSSpe), wheat ‘Simonida’ (WSSim), oat ‘Golozrni’ (OSG) and oat ‘Jadar’ (OSJ). OSG expressed significantly higher (P ≤ 0.05) total phenols (TPC) and flavonoids content (TFC), antioxidant capacities (DPPH and ABTS assays) and reducing power (EC₅₀^DPPH = 2.12 mg/ml; EC₅₀^ABTS = 0.87 mg/ml; EC_0.5^RP = 12.24 mg/ml) as well as anti‐hyperglycemic activity (EC₅₀^AHgA = 0.96 mg/ml). WSSpe had the highest content of chlorophyll (131.23 mg/100 g) and carotenoids (22.84 mg/100 g). WSSim possessed the most potent anti‐inflammatory activity (2.71 mg/ml), though not significantly different from OSG (2.77 mg/ml). The in vitro simulation of gastro‐intestinal digestion showed higher release of phenolic compounds in intestinal than in gastric fluid.     

Direct Asymmetric anti‐Mannich‐Type Reactions Catalyzed by Cinchona Alkaloid Derivatives

A series of cinchona alkaloid derivatives were used to catalyze the asymmetric anti‐Mannich‐type reaction of 3‐methyl‐2‐oxindole with N‐tosyl aryl aldimines. The resulting anti‐3,3‐disubstituted 2‐oxindole products were obtained in good yields (up to 92%) with high diastereo‐ and enantioselectivities (anti/syn up to 97:3 and 91% ee). Chirality 26:801–805, 2014. © 2014 Wiley Periodicals, Inc.     

The ‘sparkle’ in fake eyes – the protective effect of mimic eyespots in lepidoptera

Many species of lepidoptera bear conspicuous circular patterns on their wings, known as eyespots, that are hypothesised to protect their bearers against predatory birds. In this study, we focus on a small but ubiquitous feature occurring naturally in lepidopteran eyespots, namely the so‐called ‘sparkle’. The ‘pupil’ in an eyespot is often highlighted by a ‘sparkle’, which is hypothesised to mimic a natural corneal total light reflection evident as a highlight, twinkle, or sparkle in the vertebrate eye. In a study exploring the presence of such sparkles, we found that 53% of lepidopteran eyespots exceeding 1 mm in diameter have a central, pinpoint‐like ‘sparkle’, 12% have a marginal, crescent‐shaped ‘sparkle’, 13% have a semi‐circular ‘sparkle’, and 22% have an intermediate semi‐circular to crescent‐shaped ‘sparkle’. In the lepidopterans’ natural resting position, the marginal ‘sparkles’ are positioned in the upper part of the eyespots’‘pupil’ and thus may create the illusion of a spherical eyeball. The ‘sparkles’ in lepidopteran eyespots do not only appear white to humans, but also reflect ultraviolet light. White and UV‐reflecting ‘sparkles’ also appear ‘white’ for UV‐sensitive viewers such as birds, and thus may effectively mimic the natural highlight in vertebrate eyes as an area of total light reflection. In field experiments using lepidopteran dummies baited with a mealworm, we show that the ‘sparkle’ is one of several components of eyespots eliciting a deterrent effect and that eyespots with a ‘sparkle’ in a natural position have a stronger deterrent effect than those with a ‘sparkle’ in an unnatural position. These findings support the eye mimicry hypothesis that better vertebrate eye mimicry improves the deterrent effect of eyespots.     

Anti‐Stokes fluorescence from endogenously formed protoporphyrin IX – Implications for clinical multiphoton diagnostics

Multiphoton imaging based on two‐photon excitation is making its way into the clinics, particularly for skin cancer diagnostics. It has been suggested that endogenously formed protoporphyrin IX (PpIX) induced by aminolevulinic acid or methylaminolevulinate can be applied to improve tumor contrast, in connection to imaging of tissue autofluorescence. However, previous reports are limited to cell studies and data from tissue are scarce. No report shows conclusive evidence that endogenously formed PpIX increases tumor contrast when performing multiphoton imaging in the clinical situation. We here demonstrate by spectral analysis that two‐photon excitation of endogenously formed PpIX does not provide additional contrast in superficial basal cell carcinomas. In fact, the PpIX signal is overshadowed by the autofluorescent background. The results show that PpIX should be excited at a wavelength giving rise to one‐photon anti‐Stokes fluorescence, to overcome the autofluorescent background. Thus, this study reports on a plausible method, which can be implemented for clinical investigations on endogenously formed PpIX using multiphoton microscopy (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Decreasing water availability across the globe improves the effectiveness of protective ant–plant mutualisms: a meta‐analysis

Abiotic conditions can increase the costs of services and/or the benefits of rewards provided by mutualistic partners. Consequently, in some situations, the outcome of mutualisms can move from beneficial to detrimental for at least one partner. In the case of protective mutualisms between ant bodyguards and plants bearing extrafloral nectaries (EFNs), plants from arid environments face a trade‐off between EFN production and maintenance and water and carbon economy. This trade‐off may increase EFN costs and decrease their value as a defensive strategy to plants in such environments. Despite this, the presence of EFNs is an ubiquitous trait in plants from arid environments, suggesting that they provide greater benefits to plants in these environments to compensate for their higher costs. We used a meta‐analysis to investigate if such benefits do increase with decreasing water availability and the possible underlying causes (such as ant behaviour or ant diversity). As predicted, ant effect on EFN plants performance increased as mean annual precipitation decreased. We also found that the frequency of dominant ants on EFN plants increased in drier areas. Due to the more aggressive behaviour of dominant ants, we suggest that they represent an important factor shaping the adaptive value of EFNs to plants in arid environments.     

Study on the influence of caffeic acid against sodium valproate–induced nephrotoxicity in rats

Renal injury is a hallmark adverse reaction to sodium valproate (SVP), and caffeic acid (CAFF) is a phenolic compound that has anti‐inflammatory and antioxsidant properties. So, this investigation was assessed to evaluate the nephrotoxic potential of SVP and the defensive impact of CAFF against SVP nephrotoxicity. SVP was given at a dose of 500 mg/kg (i.p.) once daily for 2 weeks, while CAFF was given at a dose of 50 mg/kg (orally), simultaneously with SVP. Concurrent treatment with CAFF reduced urea and creatinine, lipid peroxidation (malondialdehyde), tumor necrosis factor alpha (TNF‐α), interferon gamma (IFN‐γ), nuclear factor kappa B (NF‐κB/p65), and transforming growth factor β (TGF‐β) levels. However, with increased glutathione content, CAFF also halted the activated Notch signaling cascade. Furthermore, CAFF suppressed caspase‐3 and inducible nitric oxide synthase expressions. To conclude, on the basis of the results obtained, CAFF proved to protect against SVP‐induced nephrotoxicity via its antioxidant, anti‐inflammatory, and antiapoptotic properties.     

High efficacy and minimal peptide required for the anti‐angiogenic and anti‐hepatocarcinoma activities of plasminogen K5

Kringle 5(K5) is the fifth kringle domain of human plasminogen and its anti‐angiogenic activity is more potent than angiostatin that includes the first four kringle fragment of plasminogen. Our recent study demonstrated that K5 suppressed hepatocarcinoma growth by anti‐angiogenesis. To find high efficacy and minimal peptide sequence required for the anti‐angiogenic and anti‐tumour activities of K5, two deletion mutants of K5 were generated. The amino acid residues outside kringle domain of intact K5 (Pro452‐Ala542) were deleted to form K5mut1(Cys462‐Cys541). The residue Cys462 was deleted again to form K5mut2(Met463‐Cys541). K5mut1 specifically inhibited proliferation, migration and induced apoptosis of endothelial cells, with an apparent two‐fold enhanced activity than K5. Intraperitoneal injection of K5mut1 resulted in more potent tumour growth inhibition and microvessel density reduction than K5 both in HepA‐grafted and Bel7402‐xenografted hepatocarcinoma mouse models. These results suggested that K5mut1 has more potent anti‐angiogenic activity than intact K5. K5mut2, which lacks only the amino terminal cysteine of K5mut1, completely lost the activity, suggesting that the kringle domain is essential for the activity of K5. The activity was enhanced to K5mut1 level when five acidic amino acids of K5 in NH₂ terminal outside kringle domain were replaced by five serine residues (K5mut3). The shielding effect of acidic amino acids may explain why K5mut1 has higher activity. K5, K5mut1 and K5mut3 held characteristic β‐sheet spectrum while K5mut2 adopted random coil structure. These results suggest that K5mut1 with high efficacy is the minimal active peptide sequence of K5 and may have therapeutic potential in liver cancer.     

Simultaneous inhibition of anti‐coagulation and inflammation: crystal structure of phospholipase A2 complexed with indomethacin at 1.4 Å resolution reveals the presence of the new common ligand‐binding site

A novel ligand‐binding site with functional implications has been identified in phospholipase A₂ (PLA₂). The binding of non‐steroidal anti‐inflammatory agent indomethacin at this site blocks both catalytic and anti‐coagulant actions of PLA₂. A group IIA PLA₂ has been isolated from Daboia russelli pulchella (Russell's viper) which is enzymatically active as well as induces a strong anti‐coagulant action. The binding studies have shown that indomethacin reduces the effects of both anti‐coagulant and pro‐inflammatory actions of PLA₂. A group IIA PLA₂ was co‐crystallized with indomethacin and the structure of the complex has been determined at 1.4 Å resolution. The structure determination has revealed the presence of an indomethacin molecule in the structure of PLA₂ at a site which is distinct from the conventional substrate‐binding site. One of the carboxylic group oxygen atoms of indomethacin interacts with Asp 49 and His 48 through the catalytically important water molecule OW 18 while the second carboxylic oxygen atom forms an ionic interaction with the side chain of Lys 69. It is well known that the residues, His 48 and Asp 49 are essential for catalysis while Lys 69 is a part of the anti‐coagulant loop (residues, 54–77). Indomethacin binds in such a manner that it blocks the access to both, it works as a dual inhibitor for catalytic and anti‐coagulant actions of PLA₂. This new binding site in PLA₂ has been observed for the first time and indomethacin is the first compound that has been shown to bind at this novel site resulting in the prevention of anti‐coagulation and inflammation. Copyright © 2009 John Wiley & Sons, Ltd.     

Anti‐invasion effect of rosmarinic acid via the extracellular signal‐regulated kinase and oxidation–reduction pathway in Ls174‐T cells

Rosmarinic acid is a major phenylpropanoid isolated from Prunella vulgaris L., which is a composition of herbal tea for centuries in China. However, the anti‐invasion activity on Ls174‐T human colon carcinoma cells has not been studied. In this study, we investigated the anti‐metastasis functions according to wound healing assay, adhesion assay, and Transwell assay and found that rosmarinic acid could inhibit migration, adhesion, and invasion dose‐dependently. Rosmarinic acid also could decrease the level of reactive oxygen species by enhancing the level of reduced glutathione hormone. In addition, rosmarinic acid repressed the activity and expression of matrix metalloproteinase‐2,9. According to Western blot and quantitative real‐time PCR assay, rosmarinic acid may inhibit metastasis from colorectal carcinoma mainly via the pathway of extracellular signal‐regulated kinase. In animal experiment, intraperitoneal administration of 2 mg of rosmarinic acid reduced weight of tumors and the number of lung nodules significantly compared with those of control group. Therefore, these results demonstrated that rosmarinic acid can effectively inhibit tumor metastasis in vitro and in vivo. J. Cell. Biochem. 111: 370–379, 2010. © 2010 Wiley‐Liss, Inc.     

Synthesis and cardiovascular protective effects of quercetin 7‐O‐sialic acid

Oxidative stress and inflammation play important roles in the pathogenesis of cardiovascular disease (CVD). Oxidative stress‐induced desialylation is considered to be a primary step in atherogenic modification, and therefore, the attenuation of oxidative stress and/or inflammatory reactions may ameliorate CVD. In this study, quercetin 7‐O‐sialic acid (QA) was synthesized aiming to put together the cardiovascular protective effect of quercetin and the recently reported anti‐oxidant and anti‐atherosclerosis functions of N‐acetylneuraminic acid. The biological efficacy of QA was evaluated in vitro in various cellular models. The results demonstrated that 50 μM QA could effectively protect human umbilical vein endothelial cells (HUVEC, EA.hy926) against hydrogen peroxide‐ or oxidized low‐density lipoprotein‐induced oxidative damage by reducing the production of reactive oxygen species. QA attenuated hydrogen peroxide‐induced desialylation of HUVEC and lipoproteins. QA decreased lipopolysaccharide‐induced secretion of tumour necrosis factor‐α (TNF‐α) and monocyte chemoattractant protein‐1 (MCP‐1), and it significantly reduced the expression of intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1, TNF‐α and MCP‐1. Furthermore, QA effectively promoted cholesterol efflux from Raw 264.7 macrophages to apolipoprotein A‐1 and high‐density lipoprotein by up‐regulating ATP‐binding cassette transporter A1 and G1, respectively. Results indicated that the novel compound QA exhibited a better capacity than quercetin for anti‐oxidation, anti‐inflammation, cholesterol efflux promotion and biomolecule protection against desialylation and therefore could be a candidate compound for the prevention or treatment of CVD.     

Anti‐inflammatory and anti‐endotoxin properties of peptides derived from the carboxy‐terminal region of a defensin from the tick Ornithodoros savignyi

Antimicrobial peptides are small cationic peptides that possess a large spectrum of bioactivities, including antimicrobial, anti‐inflammatory and antioxidant activities. Several antimicrobial peptides are known to inhibit lipopolysaccharide (LPS)‐induced inflammation in vitro and to protect animals from sepsis. In this study, the cellular anti‐inflammatory and anti‐endotoxin activities of Os and Os‐C, peptides derived from the carboxy‐terminal of a tick defensin, were investigated. Both Os and Os‐C were found to bind LPS in vitro, albeit to a lesser extent than polymyxin B and melittin, known endotoxin‐binding peptides. Binding to LPS was found to reduce the bactericidal activity of Os and Os‐C against Escherichia coli confirming the affinity of both peptides for LPS. At a concentration of 25 µM, the nitric oxide (NO) scavenging activity of Os was higher than glutathione, a known NO scavenger. In contrast, Os‐C showed no scavenging activity. Os and Os‐C inhibited LPS/IFN‐γ induced NO and TNF‐α production in RAW 264.7 cells in a concentration‐dependent manner, with no cellular toxicity even at a concentration of 100 µM. Although inhibition of NO and TNF‐α secretion was more pronounced for melittin and polymyxin B, significant cytotoxicity was observed at concentrations of 1.56 µM and 25 µM for melittin and polymyxin B, respectively. In addition, Os, Os‐C and glutathione protected RAW 264.7 cells from oxidative damage at concentrations as low as 25 µM. This study identified that besides previously reported antibacterial activity of Os and Os‐C, both peptides have in addition anti‐inflammatory and anti‐endotoxin properties. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.