, 2008, Teramitsu et al., 2010 and Teramitsu and White, 2006). During song development, FoxP2 knockdown in Area MG-132 supplier X by lentivirus-mediated RNA interference causes inaccurate song imitation and a reduction in neural spine density ( Haesler et al., 2007). Thus, the thalamocortical–basal ganglia circuit is thought to contribute during development to song learning and vocal control in songbirds, with FoxP2 intimately involved, similar to the situation in humans ( Haesler et al., 2007, Schulz et al., 2010 and Teramitsu et al., 2010). Overall, these results suggest that the FoxP2 expression pattern in the thalamocortical–basal

ganglia circuit is conserved between marmoset and other species. The IO is important for learning and timing of motor control ( De Zeeuw et al., 1998), and is closely associated with the cerebellum. Jurgens and Richter (1986) reported that vocalizations can be induced by electrically stimulating the IO ( Jurgens & Richter, 1986). Therefore, although the relationship between the IO and

speech is unclear, it may be associated with vocalization in humans. Future studies are necessary to investigate the role of the IO and speech disorder-related genes in vocalization. Almost all speech impairments and reading disabilities are Buparlisib nmr learning disorders, prevalent in childhood. Most of the genes associated with these disorders play important roles in neural development, yet show different expression Celecoxib patterns in different brain areas. Furthermore, expression levels or patterns of these genes also changed during development in the marmoset brain (Table 2). Non-human primates do not have language or acquire

vocalization in the way that humans do, because of differing neuroanatomical connectivity of the auditory–vocal regions between humans and non-human primates. The arcuate fasciculus is a white-matter fiber tract that links the lateral temporal cortex with the frontal cortex, via a dorsal projection that arches around the Sylvian fissure (Rilling et al., 2008). The arcuate fasciculus shows significant differences between human and monkey brain, with projections to the middle and inferior temporal gyrus absent in monkey (Thiebaut de Schotten, Dell’Acqua, Valabregue, & Catani, 2012). In addition, from the point of view of vocal learning, direct connections between the telencephalon and medullary vocal motor nucleus have been reported in a limited number of vertebrates. In mammals, direct connections between the primary motor cortex and nucleus ambiguus that controls the vocal organ, are present in humans (Iwatsubo et al., 1990, Kuypers, 1958a and Schoen, 1969), but not observed in monkeys (Jurgens, 1976, Jurgens, 2002, Kuypers, 1958b and Simonyan and Jurgens, 2002). In contrast, neural activation in the homologue of Broca’s area is observed in vocalizing marmosets using gene expression analysis of immediate early genes (Simoes et al., 2010).

The training protocol was started at this time to evaluate the role of physical training in reversing or decreasing the harmful effects of the estrogen deficiency.

Exercise training was performed in a swimming pool (180 cm × 70 cm × 60 cm) filled with tap water warmed to approximately 30–32 °C at the same time of day (14:00–16:00 pm) in all training sessions during 8 weeks. The exercise intensity was progressively increased over the first two weeks. learn more In the first day, the rats swam for 10 min, and swim time was increased until the rats were swimming for thirty minutes on the fifth day. In the second week, the swim time was increased each day until the animals could swim for 60 min while wearing a caudal dumbbell, weighing 5% of their body weight (overload) [43]. This protocol has previously been characterized as low to moderate intensity (with a long duration) based on improvements in muscle oxidative capacity [33]. The coronary function of rats was evaluated using the Langendorff preparation (Hugo Sachs Electronics™, March-Hugstetten, Germany). Forty-eight hours after the last exercise session, the animals were killed

by decapitation. After decapitation, their thorax was opened and the hearts were rapidly excised and placed in ice-cold modified Krebs buffer. The aorta was immediately cannulated with a 21 G needle and perfused with a modified Krebs buffer (composed of 120 mM NaCl, 1.26 mM CaCl2·2H2O, 5.4 mM KCl, 2.5 mM MgSO4·7H2O, 2 mM NaH2PO4·H2O, Avelestat (AZD9668) see more 27 mM NaHCO3, 1.2 mM Na2SO4, 0.03 mM EDTA, and 11 mM glucose). The Krebs buffer was equilibrated with a carbogen mixture (O2

95% + CO2 5%, White-Martins Ind., RJ, Brazil) at a constant pressure of 100 mmHg to give a pH of 7.4 and kept at 37 °C. The perfusion flow was maintained at a rate of 10 mL/min by a peristaltic pump (MS-Reglo 4-channel, Hugo Sachs Electronics™), according to the Langendorff methods [35] and [47]. After a small surgical incision in the left atrium, isovolumetric cardiac pressure was recorded with a water-filled latex balloon (Durex, London, UK) inserted into the left ventricle (LV) through a steel catheter connected to a transducer (TPS-2 Statham transducer – Incor, Sao Paulo, SP, Brazil). The LV end-diastolic pressure was set at 8–10 mmHg by adjusting the balloon volume through a spindle syringe. The coronary perfusion pressure (CPP) and intrinsic heart rate (IHR) were continuously recorded with a sidearm of the aortic cannula with a pressure transducer (P23Db Statham transducer – Incor, Sao Paulo, SP, Brazil) connected to data acquisition system (PowerLab™, ADI Instruments, Bela Vista, NSW, Australia). After a stabilization period of 40 min, baseline values of CPP and IHR were determined. Then, the responsiveness of the coronary vascular bed was evaluated. A bolus injection (100 μl) of modified Krebs’s buffer was applied to determine volume-injection-induced changes in CPP and IHR.

The results are Venetoclax concentration shown in Table 2. Since these concentrations were genotoxic, new concentrations were tested in order to find concentrations that did not induce genotoxic damages (0.5 μg/mL, 0.1 μg/mL, 0.05 μg/mL, 0.01 μg/mL, 1 ng/mL, 100 pg/mL and 10 pg/mL). From the results obtained, it was observed

that the concentrations of 1 ng/mL, 100 pg/mL and 10 pg/mL were not statistically significant in relation to the negative control. Thus, these three concentrations were used in the assessments of the antigenotoxic potential of the wasp venom. The data concerning the antigenotoxic evaluation are shown in Table 3. By the results observed, none of the concentrations tested (1 ng/mL, 100 pg/mL and 10 pg/mL) was effectively able to decrease and/or inhibit the genotoxic action of MMS. The same concentrations used in the comet assay were also used to evaluate the mutagenicity of the wasp venom (10 μg/mL,

5 μg/mL, 1 μg/mL, 0.5 μg/mL, 0.1 μg/mL, 0.05 μg/mL, 0.01 μg/mL, 1 ng/mL, 100 pg/mL and 10 pg/mL). The results are shown in Table 4. As for the genotoxic damages, the concentrations of 1 ng/mL, 100 pg/mL and 10 pg/mL were not statistically significant in relation to the negative control. Thus, these three concentrations were selected to be used in the evaluations of the antimutagenic potential of the wasp venom (Table 5). Likewise in the antigenotoxicity assay, none of the concentrations tested was able to inhibit and/or decrease the mutagenicity induced by MMS, therefore, they were not see more considered good antimutagenic agents. Venoms of social wasps are rich in biogenic

amines, biologically active peptides and proteins (Lorenzi, 2002 and Nakajima et al., 1986). Among these substances it can be highlighted the phospholipases, hyaluronidases and mastoparans. In the present study it was observed that concentrations above 10 μg/mL are able to induce death of Carnitine palmitoyltransferase II the HepG2 cells, and the concentration of 80 μg/mL was capable of inducing the death of approximately 50% of the cells. We highlight, therefore, that it is very difficult to occur exposure to this concentration, since in a single sting of vespids it can be injected into the skin only about 20 μg of the venom. This concentration can, according to Reisman and Livingston (1992), be enough to trigger the sensitization process in human beings. However, from our results the concentration of 20 μg/mL did not induce high cytotoxicity for the exposed cells. Our results also showed that, although concentrations lower than 17 μg (10 μg/mL, 5 μg/mL, 1 μg/mL, 0.5 μg/mL, 0.1 μg/mL, 0.05 μg/mL, 0.01 μg/mL) had not induced cytotoxicity for the HepG2 cells, they present a genotoxic and mutagenic potential for these cells. This capacity may have been triggered as a result of the action of several proteins present in the venom on the cell membrane, which can lead to an alteration in the permeability of these cellular structures.

The nitrate concentration in the ATES waters of systems A, B, D, E, F and G comes rarely above the detection limit and when above detection limit it stays far below the drinking water standard of 50 mg/l (e.g. maximally 2.6 mg/l in system D). An exception is ATES system C where the nitrate concentration is much higher and often above drinking water standard (Fig. 6). The reason is that the Brussels Sands aquifer at this location is a phreatic aquifer, low in organic matter

content in which the groundwater remains oxidized to a large depth. Therefore the aquifer is vulnerable to nitrate contamination especially when shallow, by fertilization nitrate rich groundwater is pumped, mixed with deeper groundwater and injected

back in the other well during the ATES operation. selleck kinase inhibitor Fig. 6 shows Afatinib solubility dmso that no trend in the concentration time series is recorded, as a result it can be assumed that the deviation from the ambient values is explained by initial mixing of groundwater during development of the wells and in the beginning of ATES operation. This mixing effect is confirmed by data from more shallow monitoring wells in the vicinity of system C, where nitrate concentrations of about 50 mg/l occur, in contrast to the nearby deep monitoring well (2-0073) where the maximal measured nitrate concentration is 2 mg/l. No temperature influence on the groundwater quality is recorded for the ATES systems in Flanders. This is in accordance with the results from other studies and could be expected as these ATES systems operate

with small temperature differences (ΔT ≤ 10) and within a narrow temperature range (about 6–16 °C). As was already stated in the research of Bonte et al., 2013c and Bonte et al., 2011b groundwater vulnerability in the deeper part of the aquifer is increased by injecting shallow groundwater, which is more influenced by human activity, over the whole length of the well screen. The largest risk hereby exists for phreatic aquifers, which are Vitamin B12 less protected against contamination. This can lead to a deteriorated quality of the water pumped in a nearby public drinking water supply well field, especially when the well screens of the drinking water wells are situated deeper than the screens of the ATES wells. The results of this study suggest however that the quality changes at the investigated sites are rather small, so that there is no immediate risk for the drinking water supply in these cases. When mixing of shallow groundwater with deeper groundwater occurs, it is clear that the changes in the water composition are made in the beginning of ATES operation or even while developing the wells as no further deterioration of groundwater quality was monitored in the investigated ATES systems.

, 1982 and Klein Breteler & Gonzalez (1986) at the same range of temperature and food concentration. The slight differences in TD were less at higher temperatures than at lower ones under similar food

conditions and were due to the difference in food concentration. On the basis of these results it should be noticed that the development of T. longicornis is not isochronal, even at optimal food concentrations ( Klein Breteler & Gonzalez 1986). Deviations from the isochronal pattern of development have been noted in other species of calanoid copepods too – Acartia spp., Centropages spp. and Eurytemora spp. ( Peterson, 2001, Leandro et al., 2006a and Leandro et al., 2006b). The first naupliar stage PD-166866 has a short duration. Development is prolonged at the N2 stage and at the C4 and C5 stages. Stage durations are approximately equal through the late naupliar

stages and early copepodid stages. The present study has also demonstrated that the mean development time for each of the model stages of T. longicornisKB is a function of both temperature in the 5–20°C range and food concentration from 25 mgC m−3 to excess, rising with decreasing temperature and food level in the studied ranges, except for some developmental stages (naupliar stages, C1, C2 and C4) for which the temperature of ca 15°C was the optimum value. Differences in D at 12.5°C were found between T. longicornisKB and T. longicornisH in similar stage groups. The slight difference in D between the two species at the naupliar stage was from 1 (under conditions of excess food) to 4.7 days and selleck chemicals llc depended on the food concentration. But D of T. longicornisKB was four times and twice as long as that of T. longicornisH for early (C1–C3) and larger (C4–C5) copepodid stages respectively in the 25–200 mgC m−3 range of food concentration. TD of T. longicornisKB was twice as long as TD of T. longicornisH. Benzatropine For example, at Food = 25 mgC m−3, TD was 68.62 days for

T. longicornisKB and 33.705 days for T. longicornisH. In the present study, the generation time N1–C5 for T. longicornisKB at all temperatures was shorter than the values found by other authors, i.e. the difference in TD is ca 12% (4 days) and 25% (9 days) at ca 10°C according to the data given by Hay et al., 1988 and McLaren, 1978 respectively. However, at 20°C, it was 26.2% (5.5 days) when results from the German Bight after Martens (1980) and the experimental data given by Person-Le Ruyet (1975) were included. Fransz et al. (1989) stated that the respective average times required for the development of T. longicornis from the Southern Bight of the North Sea was 45, 35 and 50 days in the 5–10°C, 7–12°C and 12–18°C temperature ranges. The values were obtained on the basis of field samples at different temperatures for three generations. The differences in TD between the generations were caused by different food sources, food concentrations and temperatures.

Ethical approvals for the use of clinical notes and for the research study were obtained from The

Gambian Government/MRC Laboratories Joint Ethics Committee. Written informed consent was obtained from the family. The father did not participate in the study. A detailed clinical assessment was conducted to identify the presence of any clinical signs and symptoms of rickets including; enlarged wrists or ankles, leg pain, difficulty walking and bow-leg or windswept deformity, and to discount other diseases associated with bone deformities. Bilateral radiographs were taken of knees and wrists of the affected children and were scored by a consultant paediatrician (JMP) using a 10-point scoring system developed by Thacher et al. [6]. Standard anthropometry was conducted which included weight (wt) and standing height (ht). An overnight-fasted, 2 h urine (u) sample was collected between see more the hours of 07.00 and 09.00. Acidified (HCl 10 μL/mL, laboratory reagent grade SD 1.18, Fisher Scientific UK Ltd., Loughborough, UK) urine aliquots were stored at − 20 °C C59 wnt research buy and then later transported frozen on dry ice to MRC Human Nutrition Research (HNR), Cambridge, UK for analysis. A fasting, venous blood sample was collected, in the middle of the 2 h urine collection, transferred to lithium heparin (LiHep) and EDTA-coated tubes, plasma separated by centrifugation at

4 °C and frozen at − 20 °C, and later transported frozen on dry ice to MRC HNR, where the plasma samples and the blood cell pellets were stored at − 80 °C until analysis. The plasma samples were

analysed for markers of vitamin D, Ca and P metabolism using commercially-available methods according to the manufacturers’ instructions: intact PTH (Immunoradiometric assay; DiaSorin Ltd., Berks, UK), FGF23 (C-terminal ELISA; Immutopics Inc., CA, USA), 25OHD and 1,25(OH)2D (radioimmunoassay DiaSorin, Sitaxentan MN, USA and IDS, Tyne and Wear, UK respectively). The following colorimetric methods (Cobras Fara, Roche Products Ltd, UK and Konelab™ Analyser 20i, Finland) were used to determine plasma analytes: total calcium (TCa) by methylthymol blue (Roche Unit-Kit II) and arsenazo III (Konelab™ 981367); P, ammonium molybdate (Roche Unit-Kit II and Konelab™ 981890); and total alkaline phosphatase (TALP), p-nitrophenyl phosphate at 37 °C (Roche Alp MPR2 and Konelab™ 981832). For FGF23, > 125 RU/mL was used as an upper-limit cut-off of normality. Acidified urine was used to determine urinary (u) uCa and uP employing the same colorimetric methods as for plasma and uCr was determined using the Jaffe method (Konelab™ 981832). uCa excretion was expressed as a molar ratio with uCr. Tubular maximal reabsorption of phosphate (TmP:GFR) (mmol/L) was determined in the following way: Tubular reabsorption of phosphate (TRP) = 1 − (uP/P) × (Cr/uCr), if TRP < 0.86 then TmP:GFR = TRP × P mmol/L, if TRP > 0.86 then TmP:GFR = (0.3 × TRP/1 − (0.8 × TRP)) × P mmol/L [7].

Calm water performance of high speed marine craft smaller deadrise angles are considered favourable, reducing the wetted area Ibrutinib mw and frictional resistance improving planning efficiency (Savitsky and Koelbel, 1979). However, larger deadrise angles are favourable in rough water, reducing rough water pounding and improving directional stability (Savitsky and Koelbel, 1979). The main section types and their commented effects on ride quality of high speed marine craft are summarised in Table 1. With a forward longitudinal centre of gravity (LCG) trim angle is reduced which at low speeds usually adversely affects sea keeping, making a craft directionally unstable, wet with a greater tendency to broach in following

seas and can reduce transverse stability (Savitsky and Koelbel, 1979). However, at high speeds a forward LCG usually reduces impact accelerations (Savitsky and Koelbel, 1979). Operator skill (Helmsman’s throttle and steering control) has been reported to have a significant effect on high speed marine craft motions (Nieuwenhuis, 2005, Coats and Stark, 2008 and Townsend, 2008). Helmsman’s control is therefore anticipated to be an influential factor in determining the motion exposures experienced by the crew of high speed marine craft. Human tolerance to vibration primarily depends on the complex interactions Selleckchem Trichostatin A of motion duration, direction, frequency, magnitude and biodynamical, psychological, physiological, pathological

and intra- and inter-subject variabilities. The complex interactions and their effects on humans are not fully understood (Griffin, 1990). However, whole body vibration (WBV), especially those associated with rough vehicle rides, can damage the human body (Griffin, 1998 and Waters et al., 2007). Table 2 shows a summary of WBV experimental studies, injury reports and epidemiological studies. The physical responses of the human body to vibration are commonly represented as a complex system of masses, elasticities, damping and coupling in the low frequency range defined to be below 50 Hz (NASA, 1995). The

responses over specific frequency ranges are found to exhibit Dapagliflozin resonance motions which, with sufficient magnitude are anticipated to cause significant biological effects. The resonance frequency ranges associated with various body parts and the specific symptoms and their reported motion occurrences are summarised in Table 3 and Table 4, respectively and Table 5 summarises the motion frequencies that are known to affect human performance. Exposure to these frequency ranges are probable during high speed marine craft transits. Fatigue during high speed marine craft transits reduce the physical and cognitive performance of the occupants (Myers et al., 2008, Myers et al., 2011 and McMorris et al., 2009). This fatigue is often attributed to occupants preferring to support a proportion of their weight through their legs (Gardner et al., 2002, Cripps et al.

The salinity was measured with an inductive salinometer (model MI-150). The water temperature was measured with a mercury thermometer graduated to 0.1 °C. The seaweed samples were analysed in triplicate for their proximate lipid content using the Bligh and Dyer (1959) method. Samples were homogenised with a 1:2 mixture of chloroform and methanol and incubated in the dark overnight. The residues were extracted 2–3 times

with ABT-263 research buy a small amount of chloroform and methanol. The chloroform layer was removed with a separating funnel and then vaporised in an evaporator. The lipid content was calculated by weighing the residues and was expressed as a percentage of dry weight. The fatty acids were converted to methyl esters using the method of Christie (1998). The samples were esterified in 1% sulphuric acid in absolute methanol and extracted with hexane to separate the layers. The hexane layer was washed with water containing potassium bicarbonate and dried over anhydrous sodium sulphate. The solvent was evaporated using a rotary evaporator. The fatty acid methyl esters (FAMEs) were analysed on a Shimadzu gas-liquid chromatographer equipped with a flame ionisation detector with a packing column with Hp-5 material. The carrier gas was nitrogen, and the short speed was 5 mm/min. For the identification and quantification

of FAMEs, their retention times were compared with standards. The values are Ruxolitinib nmr expressed as a percentage of the total fatty acids mixture. The variation in fatty acid composition between the species during different seasons was evaluated using principal component analysis (PCA) (SPSS IBM version 20) with the mean of three individual samples as the variables. Three principal component analyses

(PCAs) were performed Liothyronine Sodium separately on the total, saturated and unsaturated fatty acids. The outcome was plotted in two dimensions (PCA1, PCA2). The score loading was analysed and identified in the bi-plot of PCA1 versus PCA2. The seawater parameters, such as pH, salinity and temperature, showed limited variations during the different seasons (Table 1). The pH value varied between a maximum of 8.11 during spring and a minimum of 7.60 during summer, whereas the pH value during autumn was in between (7.78). The average values of water salinity decreased in the order of autumn (32.15 g/L), spring (36.21 g/L) and summer (38.32 g/L). The seasonal temperature variations followed the climate conditions. There was significant variation between the seasons, with the highest values during the summer (29.30 °C). Furthermore, the lowest values fluctuated between 21.50 °C and 20.90 °C in the autumn and spring, respectively. The seasonal variations in the total lipid content based on the dry weight of J. rubens are shown in Table 2. The highest lipid content was 2.51% in the spring, followed by 2.42% in the summer, and the lowest value was 1.56% in autumn.

Despite many controversies, several studies have shown that there is a relationship between obesity and the increase in bone mass.8 and 9 Bone tissue is highly dynamic and is in a constant state of change, basically due to three processes: bone growth, modelling and remodelling. The latter is a continuous physiological process that allows the maintenance of bone strength and it is see more regulated by the interaction amongst bone cells and a variety of systemic hormones, cytokines, growth factors and inflammatory mediators. Obese individuals have higher bone mineral density (BMD) than non-obese individuals, and this may be a protective factor

against osteoporosis and fractures.10 Obesity may inhibit hepatic synthesis of the insulin-like growth factor binding proteins (IGFBP-3). IGFBP-3 is normally

associated with hyperinsulinemia and promotes greater activity of the insulin-like growth factor (IGF-I), which together with the direct activation of IGF-I receptors by insulin stimulate the proliferation of osteoblasts.11 and 12 Several studies have shown that leptin, a hormone secreted mainly by the adipose tissue, may have an important osteogenic effect on pubertal development and skeletal maturation.9 Other studies have indicated that if this hormone is administered directly on the cerebral ventricles of leptin-deficient mice, it may cause bone loss.8 selleck However, other authors concluded that leptin is a physiological anti-resorptive factor and it plays a role in the protective effects on bone mass.13 To study the origins of obesity and its pathological consequences, different experimental models of obese animals have been used, and amongst them, the one induced by monosodium glutamate (MSG) treatment. The administration of MSG in rats and mice during the first days after birth causes lesions in the arcuate nucleus and median eminence of the hypothalamus,14 and 15 altering the normal functioning of the hypothalamus–hypophysis axis. These animals are characterised by presenting deficiency

in the (-)-p-Bromotetramisole Oxalate release of the growth hormone16, 17 and 18; reduced basal metabolic rate, with increase in lipogenesis and diminished lipolysis19; hypo- or normophagia; obesity; hyperinsulinemia20 and 21; insulin resistance20 and increase in corticosterone and leptin concentrations.22 Several studies have been conducted to investigate the relationship between obesity and several chronic-degenerative diseases that accompany this epidemic. Nevertheless, despite evidence showing the interrelationships amongst obesity, bone remodelling and periodontal disease, the literature is very restricted, requiring much research in this scientific field. The aim of this study was to evaluate the relationship between the model of obesity induced by neonatal MSG treatment and induced periodontal disease.

He is internationally recognized as one of the most influential students of aphasia of all times. As fully appropriate for someone who would make of language his primary, lifelong interest, Luigi’s early background was multilingual. He came from a Genoese family, but was born in French-speaking MEK inhibitor Montecarlo, and was educated in Italy, in the United States and in Brazil. He graduated in Medicine in 1959 with a thesis on aphasia at the University of Milan, under the supervision of Ennio De Renzi, and went on to study neurology there. From then on Milan remained his home, with some intermissions in Paris,

where he worked with Francois Lhermitte at the Centre du Langage of La Salpetriere, and in Boston, where he started a lifelong collaboration and friendship with Norman Geschwind and Deepak Pandya. He was one of the first oversea members of the Academy of Aphasia, and one of the original driving forces behind the International Neuropsychological Symposium. In the

eighties he became Director of the Neurological Department of the University of Brescia Medical School, a position he held until his retirement. If one has to choose among Luigi’s scientific achievements, the first mention is Lumacaftor research buy probably deserved by the Token test. The principles of the test and some early findings were communicated in the first post-war joint meeting of the British and Italian neurological societies, and were then published with Ennio de Renzi in a paper in Brain (1962), which has been cited more than 1200 times.

Additional, fundamental contributions are the language rehabilitation studies, the fruits of a long standing collaboration with Anna Basso and Erminio Capitani, and the anatomical papers reporting his work in Deepak Pandya’s Lab in Boston. Luigi was very amused by the introduction of the eponym Vignolo’s syndrome by one of his mentors, Arthur Benton, to designate the presence of two Gerstmann’s syndrome deficits (agraphia and acalculia) in combination with anomia and constructional apraxia (1992). Luigi has been a great mentor, even if he did not approve the academic use of Coproporphyrinogen III oxidase the term (too “ancien régime” for his taste). He trained many students during his long career, and to many of them he transmitted his passionate interest for language and its disorders. The trademark comment about him, both from old friends and occasional acquaintances, was always “a true gentleman” (“un vero signore” in Italian). He enjoyed art, in particular music, was deeply involved in contemporary affairs and in politics, and was a citizen of the world. His wisdom and knowledge, his humour and kindness will be badly missed by many. Luigi Vignolo (centre) pictured with friends and colleagues at his retirement party in Lerici, Italy, in September 2005.