Telomere shortening and survival in free-living corvids

Evidence accumulates that telomere shortening reflects lifestyle and predicts remaining lifespan, but little is known of telomere dynamics and their relation to survival under natural conditions. We present longitudinal telomere data in free-living jackdaws (Corvus monedula) and test hypotheses on telomere shortening and survival. Telomeres in erythrocytes were measured using pulsed-field gel electrophoresis. Telomere shortening rates within individuals were twice as high as the population level slope, demonstrating that individuals with short telomeres are less likely to survive. Further analysis showed that shortening rate in particular predicted survival, because telomere shortening was much accelerated during a bird''s last year in the colony. Telomere shortening was also faster early in life, even after growth was completed. It was previously shown that the lengths of the shortest telomeres best predict cellular senescence, suggesting that shorter telomeres should be better protected. We test the latter hypothesis and show that, within individuals, long telomeres shorten faster than short telomeres in adults and nestlings, a result not previously shown in vivo. Moreover, survival selection in adults was most conspicuous on relatively long telomeres. In conclusion, our longitudinal data indicate that the shortening rate of long telomeres may be a measure of ‘life stress’ and hence holds promise as a biomarker of remaining lifespan.     

The effects of different decalcification protocols on TUNEL and general cartilage staining

Apoptosis is characterized by DNA strand breaks with a 3'-OH terminus, which are analyzed by terminal deoxy(d)-UTP nick end labeling (TUNEL). Proteinase K digestion is thought to be an essential step in the TUNEL procedure. The effects of decalcifying reagents on general staining and the TUNEL assay for cartilage sections are largely unknown. The effects of these reagents on retention and integrity of DNA in chondrocytes have not been described until now. We evaluated the effects of various decalcifying solutions, including 10% EDTA, 10% citric acid, 5% trichloroacetic acid, 5% acetic acid and a commercial hydrochloric acid-based reagent, on general cartilage staining and the TUNEL assay for cartilage. The effects of proteinase K on nucleus preservation were also examined. Decalcification with 10% EDTA gave the best result for general cartilage staining. Chondrocyte DNA was retained and intact after using this reagent. Decalcification with 10% EDTA is also the safest method of decalcification if the TUNEL assay is applied to cartilage. Proteinase K digestion may have adverse effects on nucleus preservation in cartilage. Awareness of these effects is important whenever the TUNEL assay is applied.     

Telomere attrition and growth: a life‐history framework and case study in common terns

The relationship between growth and age‐specific telomere length, as a proxy of somatic state, is increasingly investigated, but observed patterns vary and a predictive framework is lacking. We outline expectations based on the assumption that telomere maintenance is costly and argue that individual heterogeneity in resource acquisition is predicted to lead to positive covariance between growth and telomere length. However, canalization of resource allocation to the trait with a larger effect on fitness, rendering that trait relatively invariant, can cause the absence of covariance. In a case study of common tern (Sterna hirundo) chicks, in which hatching order is the main determinant of variation in resource acquisition within broods, we find that body mass, but not telomere length or attrition, varies with hatching order. Moreover, body mass and growth positively predict survival to fledging, whereas telomere length and attrition do not. Using a novel statistical method to quantify standardized variance in plasticity, we estimate between‐individual variation in telomere attrition to be only 12% of that of growth. Consistent with the relative invariance of telomere attrition, we find no correlation between age‐specific body mass or growth and telomere attrition. We suggest that common tern chicks prioritize investment in long‐term somatic state (as indicated by canalization of telomere maintenance) over immediate survival benefits of growth as part of an efficient brood reduction strategy that benefits the parents. As such, interspecific variation in the growth–telomere length relationship may be explained by the extent to which parents benefit from rapid mortality of excess offspring.     

Immune activation suppresses plasma testosterone level: a meta-analysis

Females often select mates on the basis of sexual signals, which can be reliable indicators of male quality when the costliness of these signals prevents cheating. The immunocompetence handicap hypothesis (ICHH) provides a mechanistic explanation of these costs, by proposing a trade-off between immune function and sexual displays. This trade-off arises because testosterone enhances sexual signals, but suppresses immune function. Many studies have investigated the ICHH by administrating testosterone, and a recent meta-analysis found little evidence that testosterone suppressed immune function. However, another component of the ICHH, which has received less empirical interest, suggests that there may also be an interaction in the other direction, with immune activation suppressing testosterone levels. We present a meta-analysis to test for this effect. Overall, there was a strong suppressive effect of experimental immune activation on testosterone levels (r=-0.52), regardless of whether live pathogens or non-pathogenic antigens were used to challenge the immune system. The latter is important because it shows that immune activation per se suppresses testosterone levels. Thus, a trade-off between immunocompetence and sexual displays may primarily be generated by the effect of immune activation on testosterone, rather than the opposite effect that has received most attention.     

A Dutch guideline for the treatment of scoliosis in neuromuscular disorders

Background

Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is considered the primary treatment option for correcting severe scoliosis in neuromuscular disorders. Surgery in this population requires a multidisciplinary approach, careful planning, dedicated surgical procedures, and specialized after care.

Methods

The guideline is based on scientific evidence and expert opinions. A multidisciplinary working group representing experts from all relevant specialties performed the research. A literature search was conducted to collect scientific evidence in answer to specific questions posed by the working group. Literature was classified according to the level of evidence.

Results

For most aspects of the treatment scientific evidence is scarce and only low level cohort studies were found. Nevertheless, a high degree of consensus was reached about the management of patients with scoliosis in neuromuscular disorders. This was translated into a set of recommendations, which are now officially accepted as a general guideline in the Netherlands.

Conclusion

In order to optimize the treatment for scoliosis in neuromuscular disorders a Dutch guideline has been composed. This evidence-based, multidisciplinary guideline addresses conservative treatment, the preoperative, perioperative, and postoperative care of scoliosis in neuromuscular disorders.     

Differentiation of adult-type Leydig cells occurs in gonadotrophin-deficient mice

During mammalian testis development distinct generations of fetal and adult Leydig cells arise. Luteinising hormone (LH) is required for normal adult Leydig cell function and for the establishment of normal adult Leydig cell number but its role in the process of adult Leydig cell differentiation has remained uncertain. In this study we have examined adult Leydig cell differentiation in gonadotrophin-releasing hormone (GnRH)-null mice which are deficient in circulating gonadotrophins. Adult Leydig cell differentiation was assessed by measuring expression of mRNA species encoding four specific markers of adult Leydig cell differentiation in the mouse. Each of these markers (3β-hydroxysteroid dehydrogenase type VI (3βHSD VI), 17β-hydroxysteroid dehydrogenase type III (17βHSD III), prostaglandin D (PGD)-synthetase and oestrogen sulphotransferase (EST)) is expressed only in the adult Leydig cell lineage in the normal adult animal. Real-time PCR studies showed that all four markers are expressed in adult GnRH-null mice. Localisation of 3βHSD VI and PGD-synthetase expression by in situ hybridisation confirmed that these genes are expressed in the interstitial tissue of the GnRH-null mouse. Treatment of animals with human chorionic gonadotrophin increased expression of 3βHSD VI and 17βHSD III within 12 hours further indicating that differentiated, but unstimulated cells already exist in the GnRH-null mouse. Thus, while previous studies have shown that LH is required for adult Leydig cell proliferation and activity, results from the present study show that adult Leydig cell differentiation will take place in animals deficient in LH.     

Correlation between severity of sleep apnea and upper airway morphology based on advanced anatomical and functional imaging

Determination of the apnea hypopnea index (AHI) as a measure of the severity of obstructive sleep apnea/hypopnea syndrome (OSAHS) is a widely accepted methodology. However, the outcome of such a determination depends on the method used, is time consuming and insufficient for prediction of the effect of all treatment modalities. For these reasons more methods for evaluating the severity of OSAHS, based on different imaging modalities, have been looked into and recent studies have shown that anatomical properties determined from three-dimensional (3D) computed tomography (CT) images are good markers for the severity of the OSAHS. Therefore, we correlated anatomical measurements of a 3D reconstruction of the upper airway together with flow simulation results with the severity of OSAHS in order to find a combination of variables to indicate the severity of OSAHS in patients. The AHI of 20 non-selected, consecutive patients has been determined during a polysomnography. All patients also underwent a CT scan from which a 3D model of the upper airway geometry was reconstructed. This 3D model was used to evaluate the anatomical properties of the upper airway in OSAHS patients as well as to perform computational fluid dynamics (CFD) computations to evaluate the airflow and resistance of this upper airway. It has been shown that a combination of the smallest cross-sectional area and the resistance together with the body mass index (BMI) form a set of markers that predict very well the severity of OSAHS in patients within this study. We believe that these markers can be used to evaluate the outcome of an OSAHS treatment.     

Ultralong telomeres shorten with age in nestling great tits but are static in adults and mask attrition of short telomeres

Telomere length (TL) is increasingly being used as a biomarker of senescence, but measuring telomeres remains a challenge. Within tissue samples, TL varies between cells and chromosomes. Class I telomeres are (presumably static) interstitial telomeric sequences, while terminal telomeres have been divided in shorter (Class II) telomeres and ultralong (Class III) telomeres, and the presence of the latter varies strongly between species. Class II telomeres typically shorten with age, but little is known of Class III telomere dynamics. Using multiple experimental approaches, we show great tits to have ultralong telomeres, and we investigated age effects on Class II and III telomeres using a longitudinal approach (our method excludes Class I telomeres). In adults, TL averaged over the whole distribution did not significantly change with age. However, more detailed analyses showed that Class II TL did shorten with age, and, as in other species, the longest Class II telomeres within individuals shortened more quickly with age. In contrast, Class III TL did not shorten with age within individual adults. Surprisingly, we found the opposite pattern in nestlings: Class III TL shortened significantly with age, while the age effect on Class II TL was close to zero. Thus, Class III TL may provide information on developmental history, while Class II TL provides information on telomere dynamics in adulthood. These findings have practical implications for telomere studies and raise the interesting question of what causes variation in TL dynamics between chromosomes within individuals and how this is related to development.     

Evaluating spatial within plot crop variability for different management practices with an optical sensor?

Subsoil constraints to root growth exacerbate frequent water and nutrient limitations to crop yields in Mediterranean-type environments. Amelioration of subsoil constraints can relieve these limitations by opening root-access to subsoil water and nutrients. However, decisions in subsoil amelioration are hampered by seasonally variable yield responses in these environments. We used the APSIM model to analyse the impact of subsoil constraints on yield and yield variability. The simulated yield data were used to calculate the financial benefits of subsoil amelioration across several scenarios. There was a strong yield-dependence on accessible soil water governed by root depth. Root depth development was limited to a minimum of either the effect of subsoil constraints or the weather-dependent depth of the soil wetting front. Insufficient rainfall in dry years or in a drier region often resulted in shallow soil wetting fronts and correspondingly shallow roots even in the absence of subsoil compaction. In these situations, there is little response to subsoil amelioration. Positive yield responses and positive financial returns to subsoil amelioration are therefore greater in good rainfall years and are more likely in a wetter region. A yield response to amelioration is also greater in coarser textured sand than finer textured sandy loam in an average rainfall season because the same amount of rainfall results in a deeper wetting front in sand than in sandy loam. Hence, roots in a sand are required to grow deeper compared to a sandy loam to access the same amount of water and therefore benefited more from subsoil amelioration in an average rainfall year. In wet years, sands leach more nitrate than sandy loam, which decreases yields and the response to subsoil amelioration in sands is more than in the sandy loam. Environmental threats occur along with yield loss when roots cannot access subsoil water. These include increased nitrate leaching and deep drainage due to unused water remaining in the soil profile. By allowing roots to access deep soil water, ameliorating subsoil is expected to yield financial gains in average to good rainfall seasons and decrease the environmental risk of drainage and leaching loss. The financial gains are expected to offset potential financial losses in dry and dry finish seasons especially in coarser textured soils and wetter environment. Responsible Editor: Jan Vos.