Timing matters: traffic noise accelerates telomere loss rate differently across developmental stages.

BACKGROUND: Noise pollution is one of the leading environmental health risks for humans, linked to a myriad of stress-related health problems. Yet little is known about the long-term effects of noise on the health and fitness of wildlife. We experimentally investigated the direct and cross-generational effects of traffic noise on telomeres; a measure of cellular ageing that is predictive of disease and longevity in humans and other organisms. We exposed zebra finches (Taenopygia guttata) to three different treatment groups: 1) parents were exposed to traffic noise before and during breeding, together with their nestling young, 2) fledged juveniles but not their parents were exposed to traffic noise, and 3) control group birds were never exposed to traffic noise. RESULTS: Although there was no significant effect of traffic noise exposure at early (pre-fledging) stages of offspring telomere length or loss rate, traffic noise exposure accelerated telomere loss in older (post-fledging) juveniles. CONCLUSIONS: The age-dependent differences found in this study in telomere loss could occur if parents buffer younger offspring against the detrimental effects of noise exposure and/or if younger offspring are less sensitive to noise exposure. Telomere length during early life has been shown to be positively related to lifespan and the observed noise-induced increase of telomere attrition rate could reduce the fitness of the affected birds and potentially alter the population dynamics of birds in noise polluted areas. Our data highlight the need to consider the developmental stage of an organism to better understand the ecological consequences of anthropogenic change.

Universal mechanisms of sound production and control in birds and mammals.

As animals vocalize, their vocal organ transforms motor commands into vocalizations for social communication. In birds, the physical mechanisms by which vocalizations are produced and controlled remain unresolved because of the extreme difficulty in obtaining in vivo measurements. Here, we introduce an ex vivo preparation of the avian vocal organ that allows simultaneous high-speed imaging, muscle stimulation and kinematic and acoustic analyses to reveal the mechanisms of vocal production in birds across a wide range of taxa. Remarkably, we show that all species tested employ the myoelastic-aerodynamic (MEAD) mechanism, the same mechanism used to produce human speech. Furthermore, we show substantial redundancy in the control of key vocal parameters ex vivo, suggesting that in vivo vocalizations may also not be specified by unique motor commands. We propose that such motor redundancy can aid vocal learning and is common to MEAD sound production across birds and mammals, including humans.

Characterization of the melanocortin-4-receptor nonsense mutation W16X in vitro and in vivo.

Several genetic diseases are triggered by nonsense mutations leading to the formation of truncated and defective proteins. Aminoglycosides have the capability to mediate a bypass of stop mutations during translation thus resulting in a rescue of protein expression. So far no attention has been directed to obesity-associated stop mutations as targets for nonsense suppression. Herein, we focus on the characterization of the melanocortin-4-receptor (MC4R) nonsense allele W16X identified in obese subjects. Cell culture assays revealed a loss-of-function of Mc4r(X16) characterized by impaired surface expression and defect signaling. The aminoglycoside G-418 restored Mc4r(X16) function in vitro demonstrating that Mc4r(X16) is susceptible to nonsense suppression. For the evaluation of nonsense suppression in vivo, we generated a Mc4r(X16) knock-in mouse line by gene targeting. Mc4r(X16) knock-in mice developed hyperphagia, impaired glucose tolerance, severe obesity and an increased body length demonstrating that this new mouse model resembles typical characteristics of Mc4r deficiency. In a first therapeutic trial, the aminoglycosides gentamicin and amikacin induced no amelioration of obesity. Further experiments with Mc4r(X16) knock-in mice will be instrumental to establish nonsense suppression for Mc4r as an obesity-associated target gene expressed in the central nervous system.

Enhanced testosterone levels affect singing motivation but not song structure and amplitude in Bengalese finches.

Song is a fundamental component of territory defense and mate attraction in birds, and androgens (like testosterone) are known to play a key role in controlling it. However, little is known about how differences in testosterone levels between males translate into inter-individual song variation. Indeed, testosterone could affect both the motivation to sing and the structure of song itself. Here, we tested whether experimentally elevated testosterone levels in adult Bengalese finches (Lonchura striata var. domestica), an oscine bird species, have an activational effect on 1) song performance, and 2) song structure. Our results show that testosterone-treated males, in contrast to sham-control males, sang more when confronted with a female. Other performance-related traits, however, such as latency to sing and song amplitude, were not affected. Testosterone-treated males also showed no differences in our two measures of song structure: fundamental element frequency and mean song frequency. Because song structure is known to be organizationally affected by testosterone, our results, synthesized together with findings from the current literature, suggest that in oscine birds, song contains multiple messages about the signaler's hormonal status. First, song performance may reflect current hormonal condition, and second, song structure may reflect the past hormonal state.

A novel mutation Thr162Arg of the melanocortin 4 receptor gene in a Spanish children and adolescent population.

OBJECTIVE: The melanocortin 4 receptor gene (MC4R) is involved in body weight regulation. While many studies associated MC4R mutations with childhood obesity, information on MC4R mutations in Spanish children and adolescents is lacking. Our objective was to screen a population of children and adolescents from the north of Spain (Navarra) for MC4R mutations and to study the phenotypes of carriers and their families. In addition, functional assays were performed for a novel MC4R mutation. METHODS: The study was composed of 451 Spanish children and adolescents (49% boys), aged 5-18 year. According to the International Obesity Task Force (IOTF) criteria, the groups included 160 obese, 132 overweight and 159 normal-weight control subjects. RESULTS: One novel (Thr162Arg) and three known nonsynonymous mutations in the MC4R gene (Ser30Phe, Thr150Ile, Ala244Glu) were detected heterozygously. The MC4R mutations were found in three male (one obese and two overweight) and two female subjects (one obese and one overweight). The novel mutation did not appear to lead to an impaired receptor function. An unequivocal relationship of MC4R mutations with obesity in pedigrees together with an impaired function of the encoded receptor could not be established for any of the mutations. CONCLUSIONS: The presence of heterozygous MC4R mutations in obese and overweight subjects indicates that these mutations may be a susceptibility factor for obesity development, but lifestyle factors, such as exercise or sedentary activities, may modify their effect.

A novel non-synonymous mutation in the melanocortin-4 receptor gene (MC4R) in a 2-year-old Austrian girl with extreme obesity.

BACKGROUND: Functionally relevant mutations in the melanocortin-4 receptor gene ( MC4R) currently display the most common major gene/allele effect on extreme obesity. OBJECTIVE: Mutation screen of the MC4R in consecutively ascertained Austrian children and adolescents with severe obesity, to analyse the phenotype of mutation carriers and to functionally characterise novel mutations. SUBJECTS AND METHODS: 102 unrelated extremely obese children and adolescents (mean BMI 33.5+/-7.1 kg/m(2), >97th centile; mean age 13.8+/-4.1 yr) and 109 parents (79 mothers/30 fathers) of 88 of these patients were studied. The MC4R coding region was screened using denaturing high-performance liquid chromatography (dHPLC); PCR products of aberrant dHPLC pattern were re-sequenced. Signal transduction properties of mutant MC4R was investigated by challenge with the highly potent agonist NDP-alpha-MSH. Cell surface expression was determined by ELISA. Magnetic resonance imaging (MRI) of the central nervous system (CNS) was applied to a 2.3 year old index patient. Body fat and bone mineral content were assessed in three of the five mutation carriers by dual energy x-ray absorptiometry (DEXA). Oral glucose tolerance test (OGTT) was applied to some mutation carriers. RESULTS: Heterozygous carriers of two non-synonymous mutations, two polymorphisms and a silent variation were identified within the study group. (1) A novel MC4R non-synonymous mutation (S136F) was detected in a 2.3 year old girl with extreme obesity (BMI 33.2 kg/m(2), >99th centile); (2) a previously described non-synonymous mutation (V253I) was identified in an obese mother (BMI 28.1 kg/m(2)) who did not transmit this mutation to her extremely obese son; (3) two known polymorphisms (V103I and I251L) were also identified; and (4) one obese mother was carrier of a silent variation (c.594C>T; I198). Co-segregation of S136F with the obesity phenotype was shown for three generations. IN VITRO functional studies revealed a complete loss of signal transduction activity of the mutant receptor while cell surface expression was only slightly reduced compared to the wild-type receptor. CONCLUSIONS: We detected a novel non-synonymous mutation (S136F) that leads to a complete loss of MC4R function IN VITRO.

Neonatal TSH screening--an instrument of iodine supplementation monitoring in Bulgaria in comparison to Berlin--a preliminary report.

The challenge to eradicate iodine deficiency disorders (IDD) by the year 2000 worldwide will have positive consequences for more than 20 million people suffering from IDD. This is the main and common goal for the developing but also for a lot the developed countries. Sensitive tools like neonatal thyroid screening (NTS) can be used in order to make changes in iodine supplementation more transparent and to have a dynamic target oriented approach. The comparison between six districts in Bulgaria and Berlin revealed despite of some positive changes after the fortification of the iodine supplementation program still existing iodine deficiency in Bulgaria which is more profound than in Berlin in 1990. The shift to higher TSH-values in the Black-Sea region, classified by goitre-prevalence in 1956 as non-endemic for iodine deficiency, needs further investigation. Besides of iodine deficiency an influence of iodine-containing disinfectants and/or goitrogens is possible.