Estimating Ecosystem Metabolism to Entire River Networks

Ecosystems - River ecosystem metabolism (REM) is a promising cost-effective measure of ecosystem functioning, as it integrates many different ecosystem processes and is affected by both rapid...     

Natriuretic peptide-dependent lipolysis in fat cells is a primate specificity

We have recently demonstrated that natriuretic peptides (NPs), which are known for regulation of blood pressure via membrane guanylyl cyclase (GC) receptors, are lipolytic in human adipose tissue. In this study, we compared the NP control of lipolysis in adipocytes from humans, nonhuman primates (macaques), rodents (rats, mice, hamsters), and nonrodent mammals (rabbits, dogs). Isolated adipocytes from these species were exposed to increasing concentrations of atrial NP (ANP) or isoproterenol (beta-adrenergic agonist). Although isoproterenol was lipolytic in all of the species, ANP only enhanced lipolysis in human and macaque adipocytes. In primate fat cells, NP-induced lipolysis involved a cGMP-dependent pathway. Binding studies and real-time quantitative PCR assays revealed that rat adipocytes expressed a higher density of NP receptors compared with humans but with a different subtype pattern of expression; type-A GC receptors predominate in human fat cells. This was also confirmed by the weak GC-activity stimulation and the reduced cGMP formation under ANP exposure in rat adipocytes compared with human fat cells. In conclusion, NP-induced lipolysis is a primate specificity, and adipocytes from ANP-nonresponsive species present a predominance of "clearance" receptors and very low expression of "biologically active" receptors.     

GENETIC ANALYSIS OF MORNINGNESS AND EVENINGNESS

We studied the influence of genetic factors on individual differences in morningness-eveningness in a sample of Dutch twin families. Data were collected from adolescent twins (mean age 17.8 yr) and their parents (mean age of fathers 48.0 yr and of mothers 46.0 yr) and a sample of older twins (mean age 46.5 yr). Scores on morningness-eveningness were rated on a 5-point scale. Parents were more morning oriented than their children, and women were more morning oriented than men. With a twin-family study, separation of genetic and environmental influences on variation in morningness-eveningness is possible. Including parents and older twins in the study makes it possible to explore generation differences in these effects. The correlation between monozygotic twins was more than twice the correlation between dizygotic twins. This indicates that genetic effects may not operate in an additive manner. Therefore, a model that included genetic dominance was explored. Biometrical model fitting showed no sex differences for the magnitude of genetic and environmental factors. The total heritability—the sum of additive and nonadditive genetic influences—for morningness-eveningness was 44% for the younger generation and 47% for the older generation. However, the genetic correlation between the generations turned out to be lower than 0.5, suggesting that different genes for morningness-eveningness are expressed in both generations. (Chronobiology International, 18(5), 809-822, 2001)     

Distinct role of subcomplexes of the COPI coat in the regulation of ArfGAP2 activity

COPI vesicles serve for transport of proteins and membrane lipids in the early secretory pathway. Their coat protein (coatomer) is a heptameric complex that is recruited to the Golgi by the small GTPase Arf1. Although recruited en bloc, coatomer can be viewed as a stable assembly of an adaptin‐like tetrameric subcomplex (CM4) and a trimeric ‘cage’ subcomplex (CM3). Following recruitment, coatomer stimulates ArfGAP‐dependent GTP hydrolysis on Arf1. Here, we employed recombinant coatomer subcomplexes to study the role of coatomer components in the regulation of ArfGAP2, an ArfGAP whose activity is strictly coatomer‐dependent. Within CM4, we define a novel hydrophobic pocket for ArfGAP2 interaction on the appendage domain of γ₁‐COP. The CM4 subcomplex (but not CM3) is recruited to membranes through Arf1 and can subsequently recruit ArfGAP2. Neither CM3 nor CM4 in itself is effective in stimulating ArfGAP2 activity, but stimulation is regained when both subcomplexes are present. Our findings point to a distinct role of each of the two coatomer subcomplexes in the regulation of ArfGAP2‐dependent GTP hydrolysis on Arf1, where the CM4 subcomplex functions in GAP recruitment, while, similarly to the COPII system, the cage‐like CM3 subcomplex stimulates the catalytic reaction.     

Activation of alpha2-adrenergic receptors blunts epinephrine-induced lipolysis in subcutaneous adipose tissue during a hyperinsulinemic euglycemic clamp in men

The aim of this study was to investigate whether hyperinsulinemia modifies adrenergic control of lipolysis, with particular attention paid to the involvement of antilipolytic alpha2-adrenergic receptors (AR). Eight healthy male subjects (age: 23.9 +/- 0.9 yr; body mass index: 23.8 +/- 1.9) were investigated during a 6-h euglycemichyperinsulinemic clamp and in control conditions. Before and during the clamp, the effect of graded perfusions of isoproterenol (0.1 and 1 microM) or epinephrine (1 and 10 microM) on the extracellular glycerol concentration in subcutaneous abdominal adipose tissue was evaluated by using the microdialysis method. Both isoproterenol and epinephrine induced a dose-dependent increase in extracellular glycerol concentration when infused for 60 min through the microdialysis probes before and during hours 3 and 6 of the clamp. The catecholamine-induced increase was significantly lower during the clamp than before it, with the inhibition being more pronounced in hour 6 of the clamp. Isoproterenol (1 microM)-induced lipolysis was reduced by 28 and 44% during hours 3 and 6 of the clamp, respectively, whereas the reduction of epinephrine (100 microM)-induced lipolysis was significantly greater (by 63 and 70%, P < 0.01 and P < 0.04, respectively) during the same time intervals. When epinephrine was infused in combination with 100 microM phentolamine (a nonselective alpha-AR antagonist), the inhibition of epinephrine (10 microM)-induced lipolysis was only of 19 and 40% during hours 3 and 6 of the clamp, respectively. The results demonstrate that, in situ, insulin counteracts the epinephrine-induced lipolysis in adipose tissue. The effect involves 1) reduction of lipolysis stimulation mediated by the beta-adrenergic pathway and 2) the antilipolytic component of epinephrine action mediated by alpha2-ARs.     

Do diversity of plants,soil fungi and bacteria influence aggregate stability on ultramafic Ferralsols? A metagenomic approach in a tropical hotspot of biodiversity

Plant and Soil - Understanding how soil aggregate stability (MWD) is influenced by microbial diversity and abundance can be crucial for ecological restoration in severely disturbed areas. We...     

First Direct Evidence of Chalcolithic Footwear from the Near Eastern Highlands

In 2008, a well preserved and complete shoe was recovered at the base of a Chalcolithic pit in the cave of Areni-1, Armenia. Here, we discuss the chronology of this find, its archaeological context and its relevance to the study of the evolution of footwear. Two leather samples and one grass sample from the shoe were dated at the Oxford Radiocarbon Accelerator Unit (ORAU). A third leather sample was dated at the University of California-Irvine Accelerator Mass Spectrometry Facility (UCIAMS). The R_Combine function for the three leather samples provides a date range of 3627–3377 Cal BC (95.4% confidence interval) and the calibrated range for the straw is contemporaneous (3627–3377 Cal BC). The shoe was stuffed with loose, unfastened grass (Poaceae) without clear orientation which was more than likely used to maintain the shape of the shoe and/or prepare it for storage. The shoe is 24.5 cm long (European size 37), 7.6 to 10 cm wide, and was made from a single piece of leather that wrapped around the foot. It was worn and shaped to the wearer''s right foot, particularly around the heel and hallux where the highest pressure is exerted in normal gait. The Chalcolithic shoe provides solid evidence for the use of footwear among Old World populations at least since the Chalcolithic. Other 4^th millennium discoveries of shoes (Italian and Swiss Alps), and sandals (Southern Israel) indicate that more than one type of footwear existed during the 4^th millennium BC, and that we should expect to discover more regional variations in the manufacturing and style of shoes where preservation conditions permit.     

Actions and interactions of growth hormone and insulin-like growth factor-II: body and organ growth of transgenic mice

To characterize long-term actions and interactions of growth hormone (GH) and insulin-like growth factor-II (IGF-II) on postnatal body and organ growth, hemizygous phosphoenolpyruvate carboxykinase (PEPCK)-human IGF-II transgenic mice were crossed with hemizygous PEPCK-bovine GH transgenic mice. The latter are characterized by two-fold increased serum levels of IGF-I and exhibit markedly increased body, skeletal and organ growth. Four different genetic groups were obtained: mice harbouring the IGF-II transgene (I), the bGH transgene (B), or both transgenes (IB), and non- transgenic controls (C). These groups of mice have previously been studied for circulating IGF-I levels (Wolf et al., 1995a), whereas the present study deals with body and organ growth. Growth curves (week 3 to 12) were estimated by regression with linear and quadratic components of age on body weight and exhibited significantly (p < 0.001) greater linear coefficients in B and IB than in I and C mice. The linear coefficients of male I and C mice were significantly (p < 0.001) greater than those of their female counterparts, whereas this sex-related difference was absent in the bGH transgenic groups. The weights of internal organs as well as the weights of abdominal fat, skin and carcass were recorded from 3.5- to 8- month-old mice. In addition, organ weight-to-body weight-ratios (relative organ weights) were calculated. Except for the weight of abdominal fat, absolute organ weights were as a rule significantly greater in B and IB than in I and C mice. IGF-II overproduction as a tendency increased the weights of kidneys, adrenal glands, pancreas and uterus both in the absence and presence of the bGH transgene. Analysis of relative organ weights demonstrated significant (p < 0.05) effects of elevated IGF- II on the relative growth of kidneys (males and females) and adrenal glands (females), confirming our previous report on organ growth of PEPCK-IGF-II transgenic mice. In females, IGF-II and GH overproduction were additive in stimulating the growth of spleen and uterus, providing evidence for tissue-specific postnatal growth promoting effects by IGF-II in the presence of elevated IGF-I     

External validation of Adjuvant! Online breast cancer prognosis tool. Prioritising recommendations for improvement

Background

Adjuvant! Online is a web-based application designed to provide 10 years survival probability of patients with breast cancer. Several predictors have not been assessed in the original Adjuvant! Online study. We provide the validation of Adjuvant! Online algorithm on two breast cancer datasets, and we determined whether the accuracy of Adjuvant! Online is improved with other well-known prognostic factors.

Patients and Methods

The French data set is composed of 456 women with early breast cancer. The Dutch data set is composed of 295 women less than 52 years of age. Agreement between observation and Adjuvant! Online prediction was checked, and logistic models were performed to estimate the prognostic information added by risk factors to Adjuvant! Online prediction.

Results

Adjuvant! Online prediction was overall well-calibrated in the French data set but failed in some subgroups of such high grade and HER2 positive patients. HER2 status, Mitotic Index and Ki67 added significant information to Adjuvant! Online prediction. In the Dutch data set, the overall 10-year survival was overestimated by Adjuvant! Online, particularly in patients less than 40 years old.

Conclusion

Adjuvant! Online needs to be updated to adjust overoptimistic results in young and high grade patients, and should consider new predictors such as Ki67, HER2 and Mitotic Index.