Protection from diabetes-induced atherosclerosis and renal disease by D-carnosine-octylester: effects of early vs late inhibition of advanced glycation end-products in Apoe-null mice.

AIMS/HYPOTHESIS: AGEs are involved in diabetic complications and might be responsible for the phenomenon of 'hyperglycaemic memory'. D-Carnosine-octylester (DCO) has been shown to attenuate AGE formation and vascular and renal injury induced by high-fat diet in Apoe-null mice. This study aimed to verify the protective effect of DCO in atherosclerosis and renal disease induced by experimental diabetes and to discover whether reduction of AGE formation by early vs late DCO treatment provides better macro and microvascular protection. METHODS: Apoe-null mice were rendered diabetic by streptozotocin and were left untreated or were treated with DCO for 20 weeks (DCO-Extended), from week 1 to 11 (DCO-Early) or from week 9 to 19 (DCO-Late). Non-diabetic Apoe-null mice served as controls. Aortic and renal lesions were evaluated by morphometry and protein and gene expression of disease markers were assessed by immunohistochemistry and real-time PCR. RESULTS: DCO-Extended treatment produced a more stable plaque phenotype by markedly attenuating diabetes-induced increases in lesion size, necrotic core area and plaque content of Nε-carboxymethyllysine, levels of apoptotic cells and markers of inflammation and oxidative stress and also reductions in collagen and smooth muscle cells. DCO treatment for 11 weeks afforded partial protection and this was significantly better in DCO-Early mice than in DCO-Late mice. Renal disease was attenuated in DCO-Extended mice and to a lesser extent in those treated for 11 weeks, with no significant difference between DCO-Early mice and DCO-Late mice. CONCLUSIONS/INTERPRETATION: These data show that DCO protects mice from diabetes-induced vascular and renal disease and that protection against atherosclerosis is more effectively achieved by early treatment than by late treatment, thus suggesting that early inhibition of AGE formation attenuates progression of macroangiopathy and favours development of more stable lesions.

The purinergic 2X7 receptor participates in renal inflammation and injury induced by high-fat diet: possible role of NLRP3 inflammasome activation.

Renal disease associated with type 2 diabetes and the metabolic syndrome is characterized by a distinct inflammatory phenotype. The purinergic 2X7 receptor (P2X7 R) and the nucleotide-binding and oligomerization domain-like receptor containing a pyrin domain 3 (NLRP3) inflammasome have been separately shown to play a role in two models of non-metabolic chronic kidney disease. Moreover, the NLRP3 inflammasome has been implicated in chronic low-grade sterile inflammation characterizing metabolic disorders, though the mechanism(s) involved in inflammasome activation under these conditions are still unknown. We investigated the role of P2X7 R (through activation of the NLRP3 inflammasome) in renal inflammation and injury induced by a high-fat diet, an established model of the metabolic syndrome. On a high-fat diet, mice lacking P2X7 R developed attenuated renal functional and structural alterations as well as reduced inflammation, fibrosis, and oxidative/carbonyl stress, as compared with wild-type animals, in the absence of significant differences in metabolic parameters. This was associated with blunted up-regulation of the NLRP3 inflammasome components NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), pro-caspase 1, pro-interleukin (IL)-1ß, and pro-IL-18, as well as reduced inflammasome activation, as evidenced by decreased formation of mature caspase 1, whereas mature IL-1ß and IL-18 were not detected. Up-regulated expression of NLRP3 and pro-caspase 1, post-translational processing of pro-caspase-1, and release of IL-18 in response to lipopolysaccharide + 2'(3')-O-(4-benzoylbenzoyl)ATP were attenuated by P2X7 R silencing in cultured mouse podocytes. Protein and mRNA expression of P2X7 R, NLRP3, and ASC were also increased in kidneys from subjects with type 2 diabetes and the metabolic syndrome, showing histologically documented renal disease. These data provide evidence of a major role for the purinergic system, at least in part through activation of the NLRP3 inflammasome, in the process driving 'metabolic' renal inflammation and injury and identify P2X7 R and NLRP3 as novel therapeutic targets.

Galectin-3 in diabetic patients.

Galectin-3 is a versatile molecule which exerts several and sometimes opposite functions in various pathophysiological processes. Recently, galectin-3 has gained attention as a powerful predictor of heart failure and mortality, thus becoming a useful prognostic marker in clinical practice. Moreover, though not specifically investigated in diabetic cohorts, plasma levels of galectin-3 correlated with the prevalence of diabetes and related metabolic conditions, thus suggesting that pharmacological blockade of this lectin might be successful for treating heart failure especially in subjects suffering from these disorders. Indeed, galectin-3 is considered not only as a marker of heart failure, but also as a mediator of the disease, due to its pro-fibrotic action, though evidence comes mainly from studies in galectin-3 deficient mice. However, these studies have provided contrasting results, with either attenuation or acceleration of organ fibrosis and inflammation, depending on the experimental setting and particularly on the levels of advanced glycation endproducts (AGEs)/advanced lipoxidation endproducts (ALEs), of which galectin-3 is a scavenging receptor. In fact, under conditions of increased AGE/ALE levels, galectin-3 ablation was associated with tissue-specific outcomes, reflecting the AGE/ALE-receptor function of this lectin. Conversely, in experimental models of acute inflammation and fibrosis, galectin-3 deficiency resulted in attenuation of tissue injury. There is a need for prospective studies in diabetic patients specifically investigating the relation of galectin-3 levels with complications and for further animal studies in order to establish the effective role of this lectin in organ damage before considering its pharmacological blockade in the clinical setting.

Neural correlates of successful emotion recognition in healthy elderly: a multimodal imaging study.

The ageing process is associated with reduced emotional recognition (ER) performance. The ER ability is an essential part of non-verbal communication, and its role is crucial for proper social functioning. Here, using the 'Cambridge Centre for Ageing and Neuroscience cohort sample', we investigated when ER, measured using a facial emotion recognition test, begins to consistently decrease along the lifespan. Moreover, using structural and functional MRI data, we identified the neural correlates associated with ER maintenance in the age groups showing early signs of ER decline (N = 283; age range: 58-89 years). The ER performance was positively correlated with greater volume in the superior parietal lobule, higher white matter integrity in the corpus callosum and greater functional connectivity in the mid-cingulate area. Our results suggest that higher ER accuracy in older people is associated with preserved gray and white matter volumes in cognitive or interconnecting areas, subserving brain regions directly involved in emotional processing.

Enabling people with intellectual and other disabilities to make verbal requests using cardboard chips with mini objects or pictures and a smartphone.

Objective: This study aimed to help six participants with intellectual disability combined with sensory and motor impairments to make verbal requests through the use of a technology system involving cardboard chips and a smartphone. Method: The participants were divided into two groups of three based on whether they did or did not have visual skills. Each group was exposed to the intervention with the technology system according to a non-concurrent multiple baseline across participants design. During the 20 min intervention sessions, the participants were provided with a smartphone and nine cardboard chips each of which had a picture or object (i.e., a mini object replica or raised object contour) and several radio frequency identification tags attached to it. To make a request, the participants were to bring a cardboard chip in contact with the smartphone. This read the tags attached to the cardboard and verbalized the request related to that cardboard. Results: During the baseline (without cardboard chips and smartphone), the participants' mean frequency of independent requests (all non-verbal requests) varied between zero and near 1.5 per session. During the intervention (with cardboard chips and smartphone), the participants' mean frequency of independent requests (all verbal requests) varied between over 4.5 and about 10 per session. Conclusion: The results suggest that the system might be useful to help participants like the ones included in this study to make verbal requests with simple responses.

Galectin-3 ablation protects mice from diet-induced NASH: a major scavenging role for galectin-3 in liver.

BACKGROUND & AIMS: Excess fatty acid oxidation and generation of reactive carbonyls with formation of advanced lipoxidation endproducts (ALEs) is involved in nonalcoholic steatohepatitis (NASH) by triggering inflammation, hepatocyte injury, and fibrosis. This study aimed at verifying the hypothesis that ablation of the ALE-receptor galectin-3 prevents experimental NASH by reducing receptor-mediated ALE clearance and downstream events. METHODS: Galectin-3-deficient (Lgals3(-/-)) and wild type (Lgals3(+/+)) mice received an atherogenic diet or standard chow for 8 months. Liver tissue was analyzed for morphology, inflammation, cell and matrix turnover, lipid metabolism, ALEs, and ALE-receptors. RESULTS: Steatosis was significantly less pronounced in Lgals3(-/-) than Lgals3(+/+) animals on atherogenic diet. NASH, invariably detected in Lgals3(+/+) mice, was observed, to a lower extent, only in 3/8 Lgals3(-/-) mice, showing less inflammatory, degenerative, and fibrotic phenomena than Lgals3(+/+) mice. This was associated with higher circulating ALE levels and lower tissue ALE accumulation and expression of other ALE-receptors. Up-regulation of hepatic fatty acid synthesis and oxidation, inflammatory cell infiltration, pro-inflammatory cytokines, endoplasmic reticulum stress, hepatocyte apoptosis, myofibroblast transdifferentiation, and impaired Akt phosphorylation were also significantly attenuated in Lgals3(-/-) animals. Galectin-3 silencing in liver endothelial cells resulted in reduced N(ε)-carboxymethyllysine-modified albumin uptake and ALE-receptor expression. CONCLUSIONS: Galectin-3 ablation protects from diet-induced NASH by decreasing hepatic ALE accumulation, with attenuation of inflammation, hepatocyte injury, and fibrosis. It also reduced up-regulation of lipid synthesis and oxidation causing less fat deposition, oxidative stress, and possibly insulin resistance. These data suggest that galectin-3 is a major receptor involved in ALE uptake by the liver.

Accelerated lipid-induced atherogenesis in galectin-3-deficient mice: role of lipoxidation via receptor-mediated mechanisms.

OBJECTIVE: Modified lipoproteins, particularly oxidized LDLs, are believed to evoke an inflammatory response which participates in all stages of atherosclerosis. Disposal of these particles is mediated through receptors which may trigger proinflammatory signaling pathways leading to vascular injury. This study was aimed at assessing the role in atherogenesis of one of these receptors, galectin-3. METHODS AND RESULTS: Galectin-3-deficient and wild-type mice were fed an atherogenic diet or standard chow for 8 months. Lesion area and length were higher in galectin-3-deficient versus wild-type mice. At the level of the aortic sinus, wild-type animals showed only fatty streaks, whereas galectin-3-deficient mice developed complex lesions, associated with extensive inflammatory changes. This was indicated by the presence of T lymphocytes with activated Th1-phenotype and by more marked monocyte-macrophage infiltration, inflammatory mediator expression, vascular cell apoptosis, and proinflammatory transcription factor activation. Increased accumulation of oxidixed LDLs and lipoxidation products and upregulation of other receptors for these compounds, including the proinflammatory RAGE, were detected in galectin-3-deficient versus wild-type mice. CONCLUSIONS: These data suggest a unique protective role for galectin-3 in the uptake and effective removal of modified lipoproteins, with concurrent downregulation of proinflammatory pathways responsible for atherosclerosis initiation and progression.

Advanced lipoxidation end-products mediate lipid-induced glomerular injury: role of receptor-mediated mechanisms.

Atherosclerosis and renal disease are related conditions, sharing several risk factors. This includes hyperlipidaemia, which may result in enhanced lipoprotein accumulation and chemical modification, particularly oxidation, with formation of advanced lipoxidation endproducts (ALEs). We investigated whether increased lipid peroxidation plays a major role in the pathogenesis of lipid-induced renal disease, via receptor-mediated mechanisms involving the scavenger and advanced glycation endproduct (AGE) receptors. Mice knocked out for galectin-3 (Gal3(-/-)), an AGE receptor previously shown to protect from AGE-induced renal injury, and the corresponding wild-type (Gal3(+/+)) animals, were fed an atherogenic high-fat diet (HFD; 15% fat, 1.25% cholesterol and 0.5% sodium cholate); mice fed a normal-fat diet (NFD; 4% fat) served as controls. Gal3(+/+) mice fed a HFD developed glomerular disease, as indicated by proteinuria, mesangial expansion and glomerular hypertrophy and sclerosis. Glomerular injury was associated with increased glomerular matrix protein expression, ALE and oxidized LDL content, oxidative stress, AGE and scavenger receptor expression and macrophage infiltration, with only modest renal/glomerular fat accumulation and changes in lipid metabolism. Fibrotic and inflammatory changes, together with accumulation of ALEs, such as 4-hydroxy-2-nonenal adducts and N(epsilon)-carboxymethyllysine, oxidative stress and expression of the receptor of AGEs (RAGE), were significantly more marked in Gal3(-/-) animals, whereas fat deposition and abnormalities in lipid metabolism remained modest. Thus, lipid-induced renal damage is mainly dependent on lipid peroxidation with formation of carbonyl reactive species and ALEs, which accumulate within the kidney tissue, thus triggering receptor-mediated pro-inflammatory signalling pathways, as in atherogenesis. Moreover, galectin-3 exerts a significant role in the uptake and effective removal of modified lipoproteins, with diversion of these products from RAGE-dependent pro-inflammatory pathways associated with downregulation of RAGE expression.

Nanocrystalline W3O3 polymorphs. Surfactant assisted growth steps to tailor microstructure and NO2 response.

Nanocrystalline WO3 samples are synthesized by different procedures. The first series of samples are obtained by sol-gel reaction, starting from WCI6, followed by thermal treatments in the range 300-750 degrees C. To improve the oxide microstructure, a second series of samples is obtained by submitting the xerogels, obtained from the sol-gel reaction, to prolonged (170 h) hydrothermal (HT) growth steps in the presence of a surfactant, either non-ionic (Lutensol ON70) or ionic (cetylpyridinium chloride), and to a final firing. The HT treatment, in the presence of cetylpyridinium chloride is also combined with Ag promotion (1% Ag). The phase composition of all samples is characterized jointly by XRD Rietveld refinement and Raman spectroscopy. The observed different temperature domains of the nanocrystalline WO3 polymorphs with respect to bulk systems are attributed to the occurrence of surface relaxation phenomena. TEM and SEM images show that the samples submitted to the surfactant HT treatment present a generally improved microstructure while the presence of Ag induces crystallite growth and sintering between the particles. The NO2 sensing measurements show for all samples that the film response decreases with the operating temperatures and is promoted by the presence of humidity. The samples obtained by the surfactant HT treatment show a much better sensor performance with respect to the other samples, the more so in the case of the cationic molecules. The role played by the HT treatment in promoting the features of the WO3 samples is discussed also on grounds of Raman analyses in the water-OH stretching region.

Technology-aided leisure and communication support in extensive neuro-motor and communication impairments.

BACKGROUND: Individuals with extensive neuro-motor impairment and lack of speech are known to remain fairly isolated and rely on others. Yet, there is only limited evidence as to how one can help them to reach a level of independence in relevant areas such as leisure and communication. This study assessed a program based on everyday technology to support leisure and communication engagement in six of those individuals. CASE REPORT: The six cases (adults) were non-ambulatory and had no speech or functional active communication. Their neurological damage was due to extensive left hemispheric hemorrhagic or ischemic lesion and to critical illness polyneuropathy aggravating a condition of neonatal encephalopathy. A smartphone-based program was developed and successfully used to enable them to access leisure activities (e.g., listening to music) and communication (e.g., sending text messages or calling the caregiver). CLINICAL REHABILITATION IMPACT: Cases like those presented in this study may reach independent and functional engagement if supported via specific, technology-aided intervention programs.

Molecular detection of field predation among larvae of two ladybird beetles is partially predicted from laboratory experiments.

Despite the fact that natural enemies can synergistically contribute to herbivore pest suppression, sometimes predators engage in intraguild predation (IGP) that might dampen trophic cascades. DNA-based gut-content analysis has become common in assessing trophic connections and biocontrol potential by predators in field systems. Here, we developed a molecular technique that can be used to unravel predation among two ladybirds, Coccinella septempunctata and Hippodamia variegata, and their shared prey, Aphis gossypii. Both ladybirds may provide effective control of the pest. Therefore, understanding their likelihood to engage in IGP is crucial for conservation biological control. Ladybird specimens were collected in melon crop. DNA extraction, primer design and evaluation were conducted. Detectability of prey DNA did not differ significantly between the two ladybirds. H. variegata exhibited higher predation on A. gossypii than C. septempunctata (90.6% vs. 70.9%) and data correction based on DNA detectability confirmed this ranking. IGP was similar among the two species, although corrected data might suggest a stronger predation by C. septempunctata. Intriguingly, IGP by C. septempunctata was lower than predicted by laboratory bioassays, possibly due to the high complexity that arises under field conditions. Implications of our results for biological control and perspectives for ecological network analysis are discussed.

Deletion of p66Shc longevity gene protects against experimental diabetic glomerulopathy by preventing diabetes-induced oxidative stress.

p66(Shc) regulates both steady-state and environmental stress-dependent reactive oxygen species (ROS) generation. Its deletion was shown to confer resistance to oxidative stress and protect mice from aging-associated vascular disease. This study was aimed at verifying the hypothesis that p66(Shc) deletion also protects from diabetic glomerulopathy by reducing oxidative stress. Streptozotocin-induced diabetic p66(Shc) knockout (KO) mice showed less marked changes in renal function and structure, as indicated by the significantly lower levels of proteinuria, albuminuria, glomerular sclerosis index, and glomerular and mesangial areas. Glomerular content of fibronectin and collagen IV was also lower in diabetic KO versus wild-type mice, whereas apoptosis was detected only in diabetic wild-type mice. Serum and renal tissue advanced glycation end products and plasma isoprostane 8-epi-prostaglandin F2alpha levels and activation of nuclear factor kappaB (NF-kappaB) were also lower in diabetic KO than in wild-type mice. Mesangial cells from KO mice grown under high-glucose conditions showed lower cell death rate, matrix production, ROS levels, and activation of NF-kappaB than those from wild-type mice. These data support a role for oxidative stress in the pathogenesis of diabetic glomerulopathy and indicate that p66(Shc) is involved in the molecular mechanism(s) underlying diabetes-induced oxidative stress and oxidant-dependent renal injury.

Behavioural and physiological responses to prey-related cues reflect higher competitiveness of invasive vs. native ladybirds.

Understanding the traits that might be linked with biological invasions represents a great challenge for preventing non-target effects on local biodiversity. In predatory insects, the ability to exploit habitats for oviposition and the physiological response to prey availability differs between species. Those species that respond more readily to environmental changes may confer to their offspring a competitive advantage over other species. Here, we tested the hypothesis that the invasive Harmonia axyridis (Coleoptera: Coccinellidae) makes better use of information from a plant-prey (Vicia faba - Aphis fabae) system compared to the native Oenopia conglobata. Y-tube olfactometer bioassays revealed that both species used olfactory cues from the system, but H. axyridis exhibited a more complete response. This species was also attracted by plants previously infested by aphids, indicating the capacity to exploit volatile synomones induced in plants by aphid attack. Oocyte resorption was investigated when different olfactory stimuli were provided under prey shortage and the readiness of new oogenesis was measured when prey was available again. H. axyridis exhibited higher plasticity in oogenesis related to the presence/absence of plant-aphid volatiles. Our results support the hypothesis that H. axyridis is more reactive than O. conglobata to olfactory cues from the plant-prey system.

Galectin-3/AGE-receptor 3 knockout mice show accelerated AGE-induced glomerular injury: evidence for a protective role of galectin-3 as an AGE receptor.

We previously showed that mice lacking galectin-3/AGE-receptor 3 develop accelerated diabetic glomerulopathy. To further investigate the role of galectin-3/AGE-receptor function in the pathogenesis of diabetic renal disease, galectin-3 knockout (KO) and coeval wild-type (WT) mice were injected for 3 months with 30 microg/day of N(epsilon)-carboxymethyllysine (CML)-modified or unmodified mouse serum albumin (MSA). Despite receiving equal doses of CML, KO had higher circulating and renal AGE levels and showed more marked renal functional and structural changes than WT mice, with significantly higher proteinuria, albuminuria, glomerular, and mesangial area and glomerular sclerosis index. Renal 4-hydroxy-2-nonenal content and NFkappaB activation were also more pronounced in KO-CML vs. WT-CML. Kidney mRNA levels of fibronectin, laminin, collagen IV, and TGF-beta were up-regulated, whereas those of matrix metalloproteinase-2 and -14 were down-regulated, again more markedly in KO-CML than WT-CML mice. Basal and CML-induced RAGE and 80K-H mRNA levels were higher in KO vs. WT mice. MSA injection did not produce any significant effect in both genotypes. The association of galectin-3 ablation with enhanced susceptibility to AGE-induced renal disease, increased AGE levels and signaling, and altered AGE-receptor pattern indicates that galectin-3 is operating in vivo as an AGE receptor to afford protection toward AGE-dependent tissue injury.

Aged titania nanoparticles: the simultaneous control of local and long-range properties.

TiO(2) nanoparticles are obtained by combining a sol-gel preparative route with hydrothermal aging steps, performed in mild conditions, of varying time lengths. Both aged and un-aged samples are thermally treated at 300 and 600 degrees C, for the same length of time. The crystal structures, the phase composition, and crystallite sizes are analyzed by powder X-ray diffraction. Raman spectra of anatase nanocrystals with average sizes of 7-10 nm are reported and the correlation between the Raman band shape of the main feature at 144 cm(-1) and the crystallite size is discussed. Nitrogen physisorption by Brunauer-Emmett-Teller (BET) method is adopted to evaluate the particles surface area and mesopore size and size distribution. The role played by the hydrothermal step in affecting the physicochemical properties of the powders is discussed also with respect to the H(2)O/TiO(2) interactions as apparent from Raman spectroscopy investigations of the O-H stretching range (3000-3800 cm(-1)).

Development and application of molecular gut-content analysis to detect aphid and coccinellid predation by Harmonia axyridis (Coleoptera: Coccinellidae) in Italy.

Despite their positive effect in reducing pest populations, exotic generalist predators sometimes become invasive and contribute to the displacement of indigenous species in the same trophic level. Although laboratory experiments have linked intraguild predation (IGP) to these interactions, field evidence and quantification of IGP are still lacking for most systems. The recent establishment of the exotic Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae) in Italy raises concern about the detrimental effect that the ladybird could have on native coccinellids. Here we assessed, under laboratory conditions, the acceptability and suitability of eggs of 2 native ladybirds, Adalia bipunctata L. and Oenopia conglobata (L.), as prey items for H. axyridis larvae. Then we developed primers for molecular gut-content analysis to detect predation by H. axyridis on the 2 ladybirds and on the aphid Eucallipterus tiliae L. Species-specific 16S primers were developed for the 3 species and laboratory feeding trials were conducted to quantify the rate of prey DNA breakdown in the gut of H. axyridis. Moreover, to field evaluate primers, H. axyridis 4th instars (n = 132) were systematically collected from linden trees in northern Italy and screened for the presence of prey DNA. Seventy-three percent and 7% of field collected H. axyridis were positive for aphid and coccinellid DNA, respectively. Predation upon aphid and A. bipunctata was lower than predicted if density dependent consumption was expected, while predation upon O. conglobata was significantly higher. Here, we provided the first evidence of IGP among feral populations of H. axyridis and indigenous ladybird beetles, occurring in Italy.

Glomerular number and size in Milan hypertensive and normotensive rats: their relationship to susceptibility and resistance to hypertension and renal disease.

OBJECTIVE: Structural analysis, including morphometric computation of glomerular size and number, was applied to analyse the divergence between propensity to hypertension and renal damage, expressed by rats of the Milan hypertensive strain (MHS) and Milan normotensive strain (MNS), respectively. DESIGN: MHS, MNS rats and progenitor Wistar rats were investigated at age 9 weeks and 9 months. Classical morphometric methods were complemented by the dissector/fractionator technique to count glomeruli. RESULTS: At 9 weeks, when nephrogenesis was completed and hypertension established, MHS rats exhibited significantly lower kidney weight, cortical volume, glomerular number and volume compared to coeval MNS rats. In Wistar rats, these parameters were similar to those of MNS rats, except for lower glomerular volume. At 9 months, MHS rats showed significantly lower expansion of glomerular volume compared to MNS and Wistar rats. MNS rats had 10% sclerotic glomeruli, which was associated with reduced renal function and heavy proteinuria; conversely, sclerosis was rare in coeval MHS and Wistar rats. Media thickness was higher, whereas lumen diameter was lower, in intrarenal arteries of MHS versus MNS rats at both time points. CONCLUSIONS: These data indicate that structural changes other than a tubular defect may play a role in the development of hypertension in MHS rats. The lack of significant glomerular hypertrophy and damage in this strain, despite reduced glomerular number, could be related to their (haemodynamic) protection from hypertensive renal disease, possibly due to the hypertrophy of intrarenal arteries. The larger size of glomeruli of MNS rats may be linked to their susceptibility to glomerulosclerosis.

Intraguild Predation Responses in Two Aphidophagous Coccinellids Identify Differences among Juvenile Stages and Aphid Densities.

(1) Intraguild predation (IGP) can occur among aphidophagous predators thus reducing their effectiveness in controlling crop pests. Among ladybirds, Coccinella septempunctata L. and Hippodamia variegata Goeze are the most effective predators upon Aphis gossypii Glov., which is an economically important pest of melon. Understanding their likelihood to engage in reciprocal predation is a key point for conservation of biological control. Here, we aim to investigate, under laboratory conditions, the level of IGP between the two above mentioned aphidophagous species. (2) Fourth-instars of the two species were isolated in petri dishes with combinations of different stages of the heterospecific ladybird and different densities of A. gossypii. The occurrence of IGP events was recorded after six hours. (3) C. septempunctata predated H. variegata at a higher rate than vice versa (70% vs. 43% overall). Higher density of the aphid or older juvenile stage of the IG-prey (22% of fourth instars vs. 74% of eggs and second instars) reduces the likelihood of predation. (4) To our knowledge, IGP between C. septempunctata and H. variegata was investigated for the first time. Results represent a baseline, necessary to predict the likelihood of IGP occurrence in the field.

The galectin-3/RAGE dyad modulates vascular osteogenesis in atherosclerosis.

AIMS: Vascular calcification correlates with inflammation and plaque instability in a dual manner, depending on the spotty/granular (micro) or sheet-like/lamellated (macro) pattern of calcification. Modified lipoproteins trigger both inflammation and calcification via receptors for advanced lipoxidation/glycation endproducts (ALEs/AGEs). This study compared the roles of galectin-3 and receptor for AGEs (RAGE), two ALEs/AGEs-receptors with diverging effects on inflammation and bone metabolism, in the process of vascular calcification. METHODS AND RESULTS: We evaluated galectin-3 and RAGE expression/localization in 62 human carotid plaques and its relation to calcification pattern, plaque phenotype, and markers of inflammation and vascular osteogenesis; and the effect of galectin-3 ablation and/or exposure to an ALE/AGE on vascular smooth muscle cell (VSMC) osteogenic differentiation. While RAGE co-localized with inflammatory cells in unstable regions with microcalcification, galectin-3 was expressed also by VSMCs, especially in macrocalcified areas, where it co-localized with alkaline phosphatase. Expression of galectin-3 and osteogenic markers was higher in macrocalcified plaques, whereas the opposite occurred for RAGE and inflammatory markers. Galectin-3-deficient VSMCs exhibited defective osteogenic differentiation, as shown by altered expression of osteogenic transcription factors and proteins, blunted activation of pro-osteoblastogenic Wnt/ß-catenin signalling and proliferation, enhanced apoptosis, and disorganized mineralization. These abnormalities were associated with RAGE up-regulation, but were only in part prevented by RAGE silencing, and were partially mimicked or exacerbated by treatment with an AGE/ALE. CONCLUSION: These data indicate a novel molecular mechanism by which galectin-3 and RAGE modulate in divergent ways, not only inflammation, but also vascular osteogenesis, by modulating Wnt/ß-catenin signalling, and independently of ALEs/AGEs.