bluuebunny/crossref_metadata_2025 huggingface dataset:
Citizen Science as an Ecological Research Tool: Challenges and Benefits
Authors: Dickinson Janis L. , Zuckerberg Benjamin , Bonter David N.
Published: November 2010

Citizen science, the involvement of volunteers in research, has increased the scale of ecological field studies with continent-wide, centralized monitoring efforts and, more rarely, tapping of volunteers to conduct large, coordinated, field experiments. The unique benefit for the field of ecology lies in understanding processes occurring at broad geographic scales and on private lands, which are impossible to sample extensively with traditional field research models. Citizen science produces large, longitudinal data sets, whose potential for error and bias is poorly understood. Because it does not usually aim to uncover mechanisms underlying ecological patterns, citizen science is best viewed as complementary to more localized, hypothesis-driven research. In the process of addressing the impacts of current, global “experiments” altering habitat and climate, large-scale citizen science has led to new, quantitative approaches to emerging questions about the distribution and abundance of organisms across space and time.
Divergence with Gene Flow: Models and Data
Authors: Pinho Catarina , Hey Jody
Published: November 2010

Since Darwin first proposed that new species could arise without geographic separation, biologists have debated whether or not divergence occurs in the presence of gene exchange. Today we understand that new species can diverge while exchanging genes, depending on the strength of disruptive natural selection and the factors that affect the linkage relationships of genes under disruptive selection. This mode of diversification—divergence with gene flow—includes sympatric speciation, in which gene exchange occurs since onset of divergence, and secondary contact following a period of geographic isolation, as well as all sorts of situations in which gene flow happens intermittently. In recent years, statistical tools have been developed that can reveal the action of gene flow during divergence. Isolation-with-migration (IM) models include parameters for population size, time of population separation, and gene exchange, and they have been used extensively to estimate levels of gene exchange. A survey of studies that have used these models shows that a plurality find little evidence of gene flow; however, many report nonzero gene exchange.
The Genetic Basis of Sexually Selected Variation
Authors: Chenoweth Stephen F. , McGuigan Katrina
Published: November 2010

Sexually selected traits contribute greatly to phenotypic diversity, yet we have historically understood little about their genetic basis and how that basis may affect their evolution. Recent work in developmental and quantitative genetics has provided both mechanistic and statistical descriptions of genotype-phenotype maps for sexually selected traits. These studies expose generally complex genetic architectures; genotype-phenotype maps are polygenic with allelic effects that are pleiotropic and highly context-dependent. At the same time, developments in quantitative genetics have provided new insights into the microevolutionary potential of standing variation and indicate genetic constraints on the contemporary evolution of male sexually selected characters, mate preferences, and also male mating success itself. Understanding the extent to which these constraints are a function of genetic architecture will require a tighter integration of developmental, molecular, and quantitative genetic approaches in a variety of model systems. Emerging genomic technologies offer an unprecedented opportunity to deepen our understanding of sexual selection as an evolutionary process.
Putting Eggs in One Basket: Ecological and Evolutionary Hypotheses for Variation in Oviposition-Site Choice
Authors: Refsnider Jeanine M. , Janzen Fredric J.
Published: November 2010

Oviposition-site choice is a major maternal effect by which females can affect the survival and phenotype of their offspring. Across oviparous species, the ultimate reasons for females' selection of oviposition sites often differ. We present six hypotheses that have been used to explain nonrandom oviposition-site choice in insects, fish, amphibians, reptiles, and birds: (a) maximizing embryo survival, (b) maximizing maternal survival, (c) modifying offspring phenotype, (d) proximity to suitable habitat for offspring, (e) maintaining natal philopatry, and (f) indirect oviposition-site choice via mate choice. Because these hypotheses differ in their relevance across oviparous taxa, each hypothesis must be tested to ensure accurate understanding of the ultimate reason behind oviposition-site choice in a particular taxon. By presenting the major hypotheses for oviposition-site choice as they relate to diverse oviparous animals, we nonetheless illustrate particular trends across animal taxa, while highlighting avenues for future research into the ecological and evolutionary drivers of oviposition-site choice.
Germination, Postgermination Adaptation, and Species Ecological Ranges
Authors: Donohue Kathleen , Rubio de Casas Rafael , Burghardt Liana , Kovach Katherine , Willis Charles G.
Published: November 2010

Germination behavior is one of the earliest phenotypes expressed by plants. This fact has several consequences for the evolution of postgermination traits, ecological niches, and geographic ranges. By determining the conditions that plants experience after they germinate, germination influences phenotypic expression of postgermination traits, natural selection on them, and their genetic basis. The breadth of germination niches may influence the ecological breadth and geographic ranges of species. Because germination is expressed early, it is frequently subjected to natural selection before other traits are expressed. We review evidence for natural selection on and adaptation of germination and discuss how the breadth of the germination niche is associated with the ecological niche and range of plant species. We review evidence for the coevolution of germination and postgermination traits and compare germination to postgermination niches. Finally, we discuss how germination responses to altered environments can influence species distribution and the evolution of postgermination traits after environmental change.
From Graphs to Spatial Graphs
Authors: Dale M.R.T. , Fortin M.-J.
Published: November 2010

Graph theory is a powerful body of mathematical knowledge, based on simple concepts, in which structural units are depicted as nodes with relationships between them depicted as lines. The nodes may have qualitative and quantitative characteristics, and the edges may have properties such as weights and directions. Graph theory provides a flexible conceptual model that can clarify the relationship between structures and processes, including the mechanisms of configuration effects and compositional differences. Graph concepts apply to many ecological and evolutionary phenomena, including interspecific associations, spatial structure, dispersal in landscapes, and relationships within metapopulations and metacommunities. We review applications of graph theory in biology, emphasizing graphs with spatial contexts. We show how spatial graph properties can be used for description and comparison as well as to test specific hypotheses. We suggest that future applications should include explicit spatial elements for landscape studies of ecological, genetic and epidemiological phenomena.
What Animal Breeding Has Taught Us about Evolution
Authors: Hill William G. , Kirkpatrick Mark
Published: November 2010

We review the impact of developments from animal breeding on our understanding of evolution and on the methodology used in evolutionary biology. The theory developed for improvement of polygenic traits, in particular the breeders' equation and the effects of finite population size, has had a significant influence. The effectiveness of within population selection is exemplified by the continued rapid genetic change, often with concomitant effects on fitness, produced by breeders. Many of the models and methods for estimation of quantitative genetic parameters, notably the animal model, have been motivated by animal breeding problems. Results from selection programs and quantitative trait loci (QTL) experiments show quantitative traits are often highly polygenic and can be adequately modeled by the infinitesimal model.
The Effect of Ocean Acidification on Calcifying Organisms in Marine Ecosystems: An Organism-to-Ecosystem Perspective
Authors: Hofmann Gretchen E. , Barry James P. , Edmunds Peter J. , Gates Ruth D. , Hutchins David A. , Klinger Terrie , Sewell Mary A.
Published: November 2010

Ocean acidification (OA), a consequence of anthropogenic carbon dioxide emissions, poses a serious threat to marine organisms in tropical, open-ocean, coastal, deep-sea, and high-latitude sea ecosystems. The diversity of taxonomic groups that precipitate calcium carbonate from seawater are at particularly high risk. Here we review the rapidly expanding literature concerning the biological and ecological impacts of OA on calcification, using a cross-scale, process-oriented approach. In comparison to calcification, we find that areas such as fertilization, early life-history stages, and interaction with synergistic stressors are understudied. Although understanding the long-term consequences of OA are critical, available studies are largely short-term experiments that do not allow for tests of long-term acclimatization or adaptation. Future research on the phenotypic plasticity of contemporary organisms and interpretations of performance in the context of current environmental heterogeneity of pCO2 will greatly aid in our understanding of how organisms will respond to OA in the future.
Transepithelial Phototherapeutic Keratectomy Using a 213-nm Solid-State Laser System Followed by Corneal Collagen Cross-Linking with Riboflavin and UVA Irradiation
Authors: Kymionis George D. , Grentzelos Michael A. , Karavitaki Alexandra E. , Kounis George A. , Kontadakis Georgios A. , Yoo Sonia , Pallikaris Ioannis G.
Published: November 2010

Purpose. To present a case of a keratoconic patient who underwent epithelial removal with transepithelial phototherapeutic keratectomy (t-PTK) using a 213-nm solid-state laser system followed by corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A (UVA) irradiation.Methods. Case report.Results. A twenty-four-year-old male with keratoconus underwent CXL treatment after epithelial removal with t-PTK using a solid-state laser system. No intra- or early postoperative complications were found. One month postoperatively, uncorrected visual acuity (UCVA) improved from 20/63 to 20/32 while best spectacle- corrected visual acuity (BSCVA) improved from 20/40 to 20/25. Corneal topography revealed a significant improvement which remained stable during the six-month followup period.Conclusions. Epithelial removal with t-PTK before CXL could improve patient's visual outcome.
Biology by Design: From Top to Bottom and Back
Authors: Fritz Brian R. , Timmerman Laura E. , Daringer Nichole M. , Leonard Joshua N. , Jewett Michael C.
Published: November 2010

Synthetic biology is a nascent technical discipline that seeks to enable the design and construction of novel biological systems to meet pressing societal needs. However, engineering biology still requires much trial and error because we lack effective approaches for connecting basic “parts” into higher-order networks that behave as predicted. Developing strategies for improving the performance and sophistication of our designs is informed by two overarching perspectives: “bottom-up” and “top-down” considerations. Using this framework, we describe a conceptual model for developing novel biological systems that function and interact with existing biological components in a predictable fashion. We discuss this model in the context of three topical areas: biochemical transformations, cellular devices and therapeutics, and approaches that expand the chemistry of life. Ten years after the construction of synthetic biology's first devices, the drive to look beyond what does exist to what can exist is ushering in an era of biology by design.
A Filled Function Approach for Nonsmooth Constrained Global Optimization
Authors: Wang Weixiang , Shang Youlin , Zhang Ying
Published: November 2010

A novel filled function is given in this paper to find a global minima for a nonsmooth
constrained optimization problem. First, a modified concept of the filled function for nonsmooth
constrained global optimization is introduced, and a filled function, which makes use of the idea of
the filled function for unconstrained optimization and penalty function for constrained optimization, is
proposed. Then, a solution algorithm based on the proposed filled function is developed. At
last, some preliminary numerical results are reported. The results show that the proposed approach
is promising.
A Phylogenetic Index for Cichlid Microsatellite Primers
Authors: Kunkle Robert D. , Reilly Christian R. L. , Renn Suzy C. P.
Published: November 2010

Microsatellites abound in most organisms and have proven useful for a range of genetic and genomic studies. Once primers have been created, they can be applied to populations or taxa that have diverged from the source taxon. We use PCR amplification, in a 96-well format, to determine the presence and absence of 46 microsatellite loci in 13 cichlid species. At least one primer set amplified a product in each species tested, and some products were present in nearly all species. These results are compared to the known phylogenetic relationships among cichlids. While we do not address intraspecies variation, our results present a phylogenetic index for the success of microsatellite PCR primer product amplification, thus providing information regarding a collection of primers that are applicable to wide range of species. Through the use of such a uniform primer panel, the potential impact for cross species would be increased.
Browsing Patterns of White-Tailed Deer Following Increased Timber Harvest and a Decline in Population Density
Authors: Crimmins Shawn M. , Edwards John W. , Ford W. Mark , Keyser Patrick D. , Crum James M.
Published: November 2010

We examined browsing patterns of white-tailed deer (Odocoileus virginianus) on a site in the central Appalachians that experienced a substantial (>50%) reduction in deer population density and an increase in the amount of timber harvest since 2001. We sampled woody browse in and immediately adjacent to 12 clearcuts ranging in age from 0–5 years postharvest in summer 2007. Clearcut-interior areas had higher woody browse abundance and browsing rates than clearcut-edge or mature forest areas. Woody browse abundance was slightly higher within individual clearcuts than in 2001 at higher population densities and lower timber harvest rates. Overall browsing rates declined from approximately 17% in 2001 to less than 5% during our study, suggesting that the combination of deer population control, and increasing the amount of timber harvest across the landscape can reduce herbivory to levels that may not impede growth and survival of forest vegetation.
Synthesis, Crystal Structures, and DNA Binding Properties of Zinc(II) Complexes with 3‐Pyridine Aldoxime
Authors: Konidaris Konstantis F. , Papi Rigini , Katsoulakou Eugenia , Raptopoulou Catherine P. , Kyriakidis Dimitrios A. , Manessi-Zoupa Evy
Published: November 2010

The employment of 3‐pyridine aldoxime, (3‐py)CHNOH, in ZnII chemistry has afforded two novel compounds: [Zn(acac)2{(3‐py)CHNOH}]·H2O (1·H2O) [where acac- is the pentane‐2,4‐dionato(‐1) ion] and [Zn2(O2CMe)4{(3‐py)CHNOH}2] (2). Complex 1·H2O crystallizes in the monoclinic space group P21/n. The ZnII ion is five‐coordinated, surrounded by four oxygen atoms of two acac- moieties and by the pyridyl nitrogen atom of the (3‐py)CHNOH ligand. Molecules of 1 interact with the water lattice molecules forming a 2D hydrogen‐bonding network. Complex 2 crystallizes in the triclinic P‐1 space group and displays a dinuclear paddle‐wheel structure. Each ZnII exhibits a perfect square pyramidal geometry, with four carboxylate oxygen atoms at the basal plane and the pyridyl nitrogen of one monodentate (3‐py)CHNOH ligand at the apex. DNA mobility shift assays were performed for the determination of the in vitro effect of both complexes on the integrity and the electrophoretic mobility of pDNA.
Wind Speed Influences on Marine Aerosol Optical Depth
Authors: O′Dowd Colin , Scannell Claire , Mulcahy Jane , Jennings S. Gerard
Published: November 2010

The Mulcahy (Mulcahy et al., 2008) power‐law parameterization, derived at the coastal Atlantic station Mace Head, between clean marine aerosol optical depth (AOD) and wind speed is compared to open ocean MODIS‐derived AOD versus wind speed. The reported AOD versus wind speed (U) was a function of ~U2. The open ocean MODIS‐derived AOD at 550 nm and 860 nm wavelengths, while in good agreement with the general magnitude of the Mulcahy parameterization, follows a power‐law with the exponent ranging from 0.72 to 2.47 for a wind speed range of 2–18 m s−1. For the four cases examined, some MODIS cases underestimated AOD while other cases overestimated AOD relative to the Mulcahy scheme. Overall, the results from MODIS support the general power‐law relationship of Mulcahy, although some linear cases were also encountered in the MODIS dataset. Deviations also arise between MODIS and Mulcahy at higher wind speeds (>15 m s−1), where MODIS‐derived AOD returns lower values as compared to Mulcahy. The results also support the suggestion than wind generated sea spray, under moderately high winds, can rival anthropogenic pollution plumes advecting out into marine environments with wind driven AOD contributing to AOD values approaching 0.3.
The Wall Properties Effect on Peristaltic Transport of Micropolar Non‐Newtonian Fluid with Heat and Mass Transfer
Authors: Eldabe N. T. , Abou-Zeid M. Y.
Published: November 2010

The problem of the unsteady peristaltic mechanism with heat and mass transfer of an incompressible micropolar non‐Newtonian fluid in a two‐dimensional channel. The flow includes the viscoelastic wall properties and micropolar fluid parameters using the equations of the fluid as well as of the deformable boundaries. A perturbation solution is obtained, which satisfies the momentum, angular momentum, energy, and concentration equations for case of free pumping (original stationary fluid). Numerical results for the stream function, temperature, and concentration distributions are obtained. Several graphs of physical interest are displayed and discussed.
Deposition and Tribological Properties of Sulfur-Doped DLC Films Deposited by PBII Method
Authors: Moolsradoo Nutthanun , Watanabe Shuichi
Published: November 2010

Sulfur-doped diamond-like carbon films (S-DLC) fabricated fromC2H2andSF6mixtures were used to study the effects of sulfur content and negative pulse bias voltage on the deposition and tribological properties of films prepared by plasma-based ion implantation (PBII). The structure and relative concentration of the films were analyzed by Raman spectroscopy and Auger electron spectroscopy. Hardness and elastic modulus of films were measured by nanoindentation hardness testing. Tribological characteristics of films were performed using a ball-on-disk friction tester. The results indicate that with the increasing sulfur content, the hardness and elastic modulus decrease. Additionally, by changing the negative pulse bias voltage from 0 kV to−5 kV, the hardness and elastic modulus increase, while the friction coefficient and specific wear rate tends to decrease. Moreover, at a negative pulse bias voltage of−5 kV and flow-rate ratio of 1 : 2, there is considerable improvement in friction coefficient of 0.05 under ambient air is due to the formation of a transfer films on the interface. The decrease in the friction coefficient of films doped with 4.9 at.% sulfur is greater under high vacuum (0.03) than under ambient air (>0.1).
Diffuse Alveolar Damage: A Common Phenomenon in Progressive Interstitial Lung Disorders
Authors: Kaarteenaho Riitta , Kinnula Vuokko L.
Published: November 2010

It has become obvious that several interstitial lung diseases, and even viral lung infections, can progress rapidly, and exhibit similar features in their lung morphology. The final histopathological feature, common in these lung disorders, is diffuse alveolar damage (DAD). The histopathology of DAD is considered to represent end stage phenomenon in acutely behaving interstitial pneumonias, such as acute interstitial pneumonia (AIP) and acute exacerbations of idiopathic pulmonary fibrosis (IPF). Acute worsening and DAD may occur also in patients with nonspecific interstitial pneumonias (NSIPs), and even in severe viral lung infections where there is DAD histopathology in the lung. A better understanding of the mechanisms underlying the DAD reaction is needed to clarify the treatment for these serious lung diseases. There is an urgent need for international efforts for studying DAD-associated lung diseases, since the prognosis of these patients has been and is still dismal.
Proof of Concept: Network and Systems Biology Approaches Aid in the Discovery of Potent Anticancer Drug Combinations
Authors: Azmi Asfar S. , Wang Zhiwei , Philip Philip A. , Mohammad Ramzi M. , Sarkar Fazlul H.
Published: November 2010

Cancer therapies that target key molecules have not fulfilled expected promises for most common malignancies. Major challenges include the incomplete understanding and validation of these targets in patients, the multiplicity and complexity of genetic and epigenetic changes in the majority of cancers, and the redundancies and cross-talk found in key signaling pathways. Collectively, the uses of single-pathway targeted approaches are not effective therapies for human malignances. To overcome these barriers, it is important to understand the molecular cross-talk among key signaling pathways and how they may be altered by targeted agents. Innovative approaches are needed, such as understanding the global physiologic environment of target proteins and the effects of modifying them without losing key molecular details. Such strategies will aid the design of novel therapeutics and their combinations against multifaceted diseases, in which efficacious combination therapies will focus on altering multiple pathways rather than single proteins. Integrated network modeling and systems biology have emerged as powerful tools benefiting our understanding of drug mechanisms of action in real time. This review highlights the significance of the network and systems biology–based strategy and presents a proof of concept recently validated in our laboratory using the example of a combination treatment of oxaliplatin and the MDM2 inhibitor MI-219 in genetically complex and incurable pancreatic adenocarcinoma. Mol Cancer Ther; 9(12); 3137–44. ©2010 AACR.
Blood Pressure in the First Year of Life in Children with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: A Pilot Study
Authors: Mooij Christiaan F. , Kapusta Livia , Otten Barto J. , Claahsen-van der Grinten Hedi L.
Published: November 2010

Aims: Evaluation of blood pressure in the first year of life in children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Methods: Twenty-four children were included. Retrospective blood pressure values, fludrocortisone dosages, and serum renin, 17-hydroxyprogesterone (17-OHP) and androstenedione levels in the first year of life were evaluated. Blood pressure values were compared to reference values. Correlations between blood pressures and serum renin levels, and the dosage of fludrocortisone were calculated. Results: Mean peak systolic blood pressure values were generally not elevated, most values were around the 50th percentile, except incidentally higher mean peak systolic blood pressure values most below the 95th percentile. No significant correlations between blood pressure and serum renin, androstenedione and 17-OHP levels and fludrocortisone dosage were found. Conclusion: In this pilot studyin CAH patients, blood pressure values do not seem to be elevated in the first year of life. Further investigations are necessary to evaluate blood pressure in the first year of life in CAH patients in more detail.
Do Bone Mineral Density, Bone Geometry and the Functional Muscle-Bone Unit Explain Bone Fractures in Healthy Children and Adolescents?
Authors: Beccard Ralf , Land Christof , Semler Oliver , Fricke Oliver , Remer Thomas , Stabrey Angelika , Schoenau Eckhard
Published: November 2010

Background/Aims: Because the increasing fracture incidence has not been understood, the present study compares variables of the muscle-bone interaction to examine the hypothesis that an impaired adaptation of bone strength to muscle forces explains this phenomenon. Methods: The forearm of 220 individuals (mean age 11.1 ± 3.2 years; range 5.5–17.4 years) was analyzed by peripheral quantitative computed tomography. Bone mineral content (BMC), bone mineral density, periosteal circumference, cortical area, strength strain index (SSI) and muscle area (MA) were measured at the distal and proximal radius of the non-dominant forearm. Maximum isometric grip force was measured by a dynamometer. The fracture history was evaluated by a questionnaire after a period of 5 ± 1.7 years. Results: During the observational period at least one fracture appeared in 78 children and adolescents (35.5%). Individuals with and without fractures were not different in age, height, weight, and body mass index. Variables of bone mineral density, bone geometry and muscle force were not different between both groups. BMC, MA and SSI were dependent on age and sex. Conclusion: Fracture risk in healthy children and adolescents is not sufficiently explained by volumetric bone mineral density, the skeletal phenotype and indices of the functional muscle-bone unit.
Polymorphisms in KCNQ1 Are Associated with Gestational Diabetes in a Korean Population
Authors: Kwak Soo Heon , Kim Tae Hyuk , Cho Young Min , Choi Sung Hee , Jang Hak C. , Park Kyong Soo
Published: November 2010

Background: Recent genome-wide association studies in East Asians have identified polymorphisms in KCNQ1 as new type 2 diabetes risk variants. The aim of this study was to investigate whether variants in KCNQ1 are associated with development of gestational diabetes mellitus (GDM) and measures of oral glucose tolerance test (OGTT) at the time of diagnosis of GDM. Methods: Three candidate single nucleotide polymorphisms (rs2074196, rs2237892, and rs2237895) were genotyped in 869 Korean GDM women and 632 nondiabetic control subjects. Insulin resistance was estimated by homeostasis model assessment and pancreatic β-cell function by the insulinogenic index at 1 h. Results: rs2074196 and rs2237892 were associated with the risk of GDM (OR 1.17, 95% CI 1.01–1.36, p = 0.039; OR 1.24, 95% CI 1.07–1.45, p = 0.0049). Furthermore, rs2237892 and rs2237895 were nominally associated with a decreased insulinogenic index at the time of GDM diagnosis (p = 0.025 and p = 0.037), whereas no association was observed with measures of insulin resistance. Conclusions: The single nucleotide polymorphisms in KCNQ1 showed a significant association with GDM in the Korean population. Although the mechanism is not yet clear, it could be possible that variants in KCNQ1 confer a risk for GDM by altering pancreatic β-cell function.
Bone Mass and Bone Metabolism Markers during Adolescence: The HELENA Study
Authors: Gracia-Marco L. , Vicente-Rodríguez G. , Valtueña J. , Rey-López J.P. , Díaz Martínez A.E. , Mesana M.I. , Widhalm K. , Ruiz J.R. , González-Gross M. , Castillo M.J. , Moreno L.A. ,   on behalf of the HELENA Study Group
Published: November 2010

Background/Aims: The assessment of bone mineral content (BMC) and density (BMD) status in children and adolescents is important for health and the prevention of diseases. Bone metabolic activity could provide early information on bone mass development. Our aim was to describe bone mass and metabolism markers according to age and Tanner stage in adolescents. Methods: Spanish adolescents (n = 345; 168 males and 177 females) aged 12.5–17.5 years participated in this cross-sectional study. Body composition variables were measured by dual-energy X-ray absorptiometry. Serum osteocalcin (n = 101), aminoterminal propeptide of type I procollagen (n = 92) and β-isomerized C-telopeptides (β-CTX, n = 65) and urine samples (β-CTX; n = 237) were analyzed by electrochemiluminescence immunoassay. Results: Analysis of covariance showed that females had higher values for BMC and BMD in most of the regions. Both males and females had a significant decrease in bone markers while sexual maturation increases (all p < 0.05). Males had an increased bone turnover compared to females (all p < 0.05, except for urine β-CTX in Tanner ≤IV). Conclusion: Our results support the evidence of dimorphic site-specific bone accretion between sexes and show an increased bone turnover in males, suggesting higher metabolic activity.
Serum Concentrations of Adrenal Steroids and Their Precursors as a Measure of Maturity of Adrenocortical Function in Very Premature Newborns
Authors: Nykänen Päivi , Heinonen Kirsti , Riepe Felix G. , Sippell Wolfgang G. , Voutilainen Raimo
Published: November 2010

Background: Relative adrenocortical insufficiency is often seen in sick premature newborns. As the human fetal adrenal cortex does not express the 3β-hydroxysteroid dehydrogenase (3β-HSD) enzyme before about 23 weeks of gestation, we hypothesized that this enzymatic step may be rate limiting in cortisol synthesis in premature infants of less than 28 weeks postmenstrual age at birth. Methods: We measured cord, first day (D0) and median fourth day (D4) serum 17-OH-pregnenolone (17-OHPreg), 17-OH-progesterone (17-OHProg), 11-deoxycortisol, cortisol (F) and dehydroepiandrosterone sulphate concentrations and calculated the substrate/product ratios in 67 infants with gestational age 23.6–33.1 weeks. Results: The mean 17-OHPreg/17-OHProg ratio as a marker of 3β-HSD activity did not differ between the gestational age groups (gestational age <28 vs. ≧28 weeks: 0.40 vs. 0.48, p = 0.52 for cord, 3.1 vs. 2.4, p = 0.25 for D0, and 1.6 vs. 1.9, p = 0.62 for D4). In addition, the 17-OHPreg/17-OHProg ratio did not differ between the infants in the lowest F tertile compared to those in the highest F tertile group, and the serum 17-OHPreg and 17-OHProg concentrations were parallel with the respective F concentrations. Conclusion: We did not find evidence of significant immaturity in adrenal 3β-HSD activity in preterm infants between 24 and 28 weeks of gestation.
Polymorphism Pro12Ala of PPARG in Prepubertal Children with Premature Adrenarche and Its Association with Growth in Healthy Children
Authors: Laakso Saila , Utriainen Pauliina , Laakso Markku , Voutilainen Raimo , Jääskeläinen Jarmo
Published: November 2010

Background: The peroxisome proliferator-activated receptor-γ2 (PPARγ2) participates in the regulation of insulin sensitivity, and has connections to the GH-IGF system and ACTH-adrenal androgen axis. We hypothesized that PPARG Pro12Ala polymorphism leading to decreased receptor activity could contribute to the premature onset of adrenarche (PA). Methods: We performed a cross-sectional association study in 73 prepubertal children with PA and 97 age- and sex-matched healthy control children. Growth data, baseline hormone levels, and the values of oral glucose tolerance test (OGTT) were compared with PPARG genotypes. Results: We found no difference in the genotype distribution of PPARG between the PA and control children. The minor Ala12 variant was associated with lower current height SD scores (SDS) in the controls, but no similar association was seen in the PA children. Birth measures and current weight for height were equal between the genotype groups in both control and PA children. The Ala12 variant was associated with trends for a lower serum IGF-I level and lower serum insulin concentration at the 120-min time point of OGTT in control children. Conclusions: The Pro12Ala genotype of PPARG was not associated with PA. The minor Ala12 variant was associated with lower height SDS in healthy prepubertal children indicating its possible effects on growth.
Pretence, Social Cognition and Self-Knowledge in Autism
Authors: Varga Somogy
Published: November 2010

This article suggests that an account of pretence based on the idea of shared intentionality can be of help in understanding autism. In autism, there seems to be a strong link between being able to engage in pretend play, understanding the minds of others and having adequate access to own mental states. Since one of the first behavioral manifestations of autism is the lack of pretend play, it therefore seems natural to investigate pretence in order to identify the nature of the central impairment in question. In mainstream theories, this has been identified as an impaired ‘theory of mind module’ or ‘mentalizing’ capacities. This paper points to some difficulties encountered by such accounts and – by drawing on research by Tomasello and Rakoczy – seeks to develop an alternative account of pretence and social cognition.
Reduced-Intensity Conditioning Using Fludarabine and Antithymocyte Globulin Alone Allows Stable Engraftment in a Patient with Dyskeratosis Congenita
Authors: Vuong L.G. , Hemmati P.G. , Neuburger S. , Terwey T.H. , Vulliamy T. , Dokal I. , le Coutre P. , Dörken B. , Arnold R.
Published: November 2010

Dyskeratosis congenita (DC) is a rare inherited disorder characterized by the triad of nail dystrophy, mucosal leukopla- kia, and reticular pigmentation. Bone marrow failure is the principal cause of early mortality, and stem cell transplantation is the only cure for these patients. However, the results of conventional hematopoietic stem cell transplantation (HSCT) for patients with DC are poor because of the high incidence of transplant-related complications. We describe the successful treatment of a 21-year-old male with DC by nonmyeloablative HSCT from a matched unrelated donor. The gene responsible for the X-linked form of DC was screened and hemizygosity for the mutation Gln31Lys was found, which is consistent with the diagnosis. The conditioning regimen consisted of only fludarabine and antithymocyte globulin. Additionally, a graft-versus-host disease (GVHD) prophylaxis was administered with cyclosporine A (CSA) and mycophenolate mofetil (MMF). The regimen was well tolerated, no severe posttransplantation complications were observed, and engraftment was rapid and complete (granulocytes on day +11 and platelets on day +13). Seven months after HSCT, the patient developed GVHD of the liver after tapering CSA which was successfully treated with prednisolone, CSA, and MMF. At the time of reporting, 3 years after HSCT, the patient remained in good clinical condition with minimal signs of chronic GVHD of the oral mucosa. Thus, we conclude that a low-intensity conditioning regimen might be sufficient to induce permanent engraftment by using matched unrelated donor HSCT in DC patients and may avoid severe organ toxicity. Although allogeneic HSCT in patients with DC will not cure the underlying genetic defect it may significantly prolong survival through effective therapy for hematologic complications.
A Severe Case of Cefoxitin-Induced Immune Hemolytic Anemia
Authors: Leaf David E. , Langer Nathaniel B. , Markowski Mark , Garratty George , Diuguid David L.
Published: November 2010

Drug-induced immune hemolytic anemia is a rare but underdiagnosed and potentially fatal condition. We report a case of severe hemolytic anemia induced by cefoxitin in a 45-year-old woman admitted with menometrorrhagia. Hemoglobin levels reached a nadir of 4.7 g/dl approximately 72 h after cefoxitin initiation, and hemolysis resolved when cefoxitin was discontinued and prednisone 1 mg/kg was initiated. A transfusion reaction workup revealed no abnormalities. Direct antiglobulin testing was weakly positive with anti-C3. The patient’s plasma and RBC eluate reacted with cefoxitin-treated RBCs but not with untreated RBCs in the presence or absence of cefoxitin.
Angiotensin II and Its Role in Tubular Epithelial to Mesenchymal Transition Associated with Chronic Kidney Disease
Authors: Burns W.C. , Thomas M.C.
Published: November 2010

Activation of the intra-renal renin-angiotensin system (RAS) and the subsequent generation of angiotensin II (Ang II) are important mediators of haemodynamic changes in both health and disease. However, the effects of locally produced Ang II are not limited to haemodynamic actions. Ang II is also an important stimulus for tubular hypertrophy with the induction of growth factors, including transforming growth factor (TGF)-β1 and connective tissue growth factor. In this article, we explore the direct pro-fibrotic effects of Ang II and its role in inducing tubular epithelial to mesenchymal transition (EMT, also known as type 2 EMT), a known mediator of renal fibrogenesis. There is accumulating evidence that Ang II is able to induce EMT by both TGF-dependent and TGF-independent actions, both in vitro and in vivo. Moreover, blockade of the RAS has synergistic renoprotective effects across a number of causally different forms of renal disease. There is hope that targeted combinations to offset angiotensin-converting enzyme escape in the setting of RAS blockade will eventually achieve the long-term efficacy that has been expected for so long.
Is Adrenocorticotropic Hormone Deficiency Really Rare in Patients with Idiopathic Growth Hormone Deficiency and Normal Thyroid Function Tests
Authors: Savas Erdeve Senay , Ocal Gonul , Berberoglu Merih , Siklar Zeynep , Hacihamdioglu Bulent
Published: November 2010

Background/Aim: It was the aim of this study to evaluate subtle adrenocorticotropic hormone deficiencies in a group of patients with idiopathic growth hormone deficiency and without thyroid-stimulating hormone deficiency. Methods: Growth hormone and cortisol responses to an insulin tolerance test of 25 patients (15 males and 10 females) were evaluated at diagnosis (11.8 ± 2.5 years) and at the time of retesting (14.6 ± 1.6 years). A cortisol response <416, 416–555 and >555 nmol/l was defined as inadequate, blunted and normal, respectively. Results: Baseline cortisol responses to the insulin tolerance test were subnormal in 10 of the 25 patients (6 had blunted responses and 4 had inadequate responses). The mean ± SD of normal, blunted and inadequate cortisol response at diagnosis was 722.2 ± 127.8, 480.4 ± 37.4 and 317.7 ± 81.7 nmol/l, respectively. Five of these patients showed improved cortisol response at retesting. Three of the 15 patients who had a normal baseline cortisol response developed blunted cortisol response at re-evaluation. The mean ± SD of normal and blunted plus inadequate cortisol response at retesting was 668.1 ± 116.1 and 467.3 ± 64 nmol/l, respectively. All patients with a subnormal cortisol level were asymptomatic. Conclusion: Asymptomatic adrenocorticotropic hormone deficiency patients should be followed up closely, and treatment should be considered in a stress situation after re-evaluation of the hypothalamic-pituitary-adrenal axis.
Oral Sodium Bicarbonate Improves Thyroid Function in Predialysis Chronic Kidney Disease
Authors: Disthabanchong Sinee , Treeruttanawanich Akarapong
Published: November 2010

Background/Aims: Metabolic acidosis (MA) in chronic kidney disease (CKD) associates with protein energy malnutrition, osteoporosis, abnormal endocrine function and increased mortality. Oral sodium bicarbonate has been shown to improve nutritional status and preserve renal function in CKD. Depressed thyroid function has been described in CKD and was believed to be related to MA. This is a prospective randomized study that examined the effect of oral sodium bicarbonate on thyroid function in predialysis CKD with MA. Methods: Predialysis CKD patients with serum total CO2 ≤22 mM were randomized into two groups. The treatment group received increasing dose of oral sodium bicarbonate until serum total CO2 was ≧24 mM. Control patients were kept on the same medications. Thyroid function tests were measured at baseline and again after 8–12 weeks. Results: All patients had a glomerular filtration rate <35 ml/min/1.73 m2. Serum total CO2 increased significantly in the treatment group and was unchanged in the control group. At baseline, over half of the patients had T3 below the lower limit of normal. At study completion, free T3 declined further in the control group, whereas free T3, total T3, free T4 and TSH rose significantly in the treatment group. Percentage changes of total CO2 from baseline were strongly associated with the changes of T3 parameters. Glomerular filtration rate was maintained in the treatment group but declined significantly in the control group. Conclusion: Oral sodium bicarbonate, through correction of MA, improved thyroid function in predialysis CKD.
Adherence to Antihypertensive Agents and Blood Pressure Control in Chronic Kidney Disease
Authors: Schmitt Kristen E. , Edie Christine F. , Laflam Paul , Simbartl Loretta A. , Thakar Charuhas V.
Published: November 2010

Background: Hypertension is a modifiable risk factor in chronic kidney disease (CKD), and medication adherence (MA) is critical in reaching the treatment goals. Patterns of MA for antihypertensive agents and its impact on blood pressure (BP) in CKD practice settings are not well studied. Methods: We examined 7,227 CKD patients receiving at least one antihypertensive prescription between 2006 and 2007. Outpatient BP measurements were averaged as high (>130/ 80 mm Hg) versus normal (others). MA was calculated using medication possession ratio (MPR = actual treatment days/total possible treatment days). Good versus Poor MA (MPR ≧0.8 vs. <0.8) groups were compared for differences in demographic, co-morbid, and laboratory variables. The relationship between MA and BP was examined by logistic regression. Results: 4,867/7,227 patients (67%) had Good MA; the frequency of patients with Good MA varied by each drug class (p < 0.0001). MPR declined with worsening CKD (stage III: MPR = 0.83 standard deviation (SD 0.18); stage IV: MPR = 0.78 (SD 0.22); stage V: MPR = 0.75 (SD 0.21); p < 0.0001). Hospitalization episodes also negatively impacted adherence. Only 35% of CKD patients had normal BP. By multivariate analysis, Poor MA was associated with high BP (odds ratio 1.23, 95% confidence interval 1.11–1.37). Conclusions: 33% of CKD patients have Poor MA for antihypertensive agents, and MA worsens with declining renal function. Poor MA is associated with a 23% greater risk of uncontrolled hypertension. Monitoring and improving adherence in CKD practice may improve outcomes.
Titin is a Target of Matrix Metalloproteinase-2
Authors: Ali Mohammad A.M. , Cho Woo Jung , Hudson Bryan , Kassiri Zamaneh , Granzier Henk , Schulz Richard
Published: November 2010

Background—

Titin is the largest mammalian (≈3000 to 4000 kDa) and myofilament protein that acts as a molecular spring in the cardiac sarcomere and determines systolic and diastolic function. Loss of titin in ischemic hearts has been reported, but the mechanism of titin degradation is not well understood. Matrix metalloproteinase-2 (MMP-2) is localized to the cardiac sarcomere and, on activation in ischemia/reperfusion injury, proteolyzes specific myofilament proteins. Here we determine whether titin is an intracellular substrate for MMP-2 and if its degradation during ischemia/reperfusion contributes to cardiac contractile dysfunction.

Methods and Results—

Immunohistochemistry and confocal microscopy in rat and human hearts showed discrete colocalization between MMP-2 and titin in the Z-disk region of titin and that MMP-2 is localized mainly to titin near the Z disk of the cardiac sarcomere. Both purified titin and titin in skinned cardiomyocytes were proteolyzed when incubated with MMP-2 in a concentration-dependent manner, and this was prevented by MMP inhibitors. Isolated rat hearts subjected to ischemia/reperfusion injury showed cleavage of titin in ventricular extracts by gel electrophoresis, which was confirmed by reduced titin immunostaining in tissue sections. Inhibition of MMP activity with ONO-4817 prevented ischemia/reperfusion-induced titin degradation and improved the recovery of myocardial contractile function. Titin degradation was also reduced in hearts from MMP-2 knockout mice subjected to ischemia/reperfusion in vivo compared with wild-type controls.

Conclusion—

MMP-2 localizes to titin at the Z-disk region of the cardiac sarcomere and contributes to titin degradation in myocardial ischemia/reperfusion injury.
Bundle-Branch Block Morphology and Other Predictors of Outcome After Cardiac Resynchronization Therapy in Medicare Patients
Authors: Bilchick Kenneth C. , Kamath Sandeep , DiMarco John P. , Stukenborg George J.
Published: November 2010

Background—

Clinical trials of cardiac resynchronization therapy (CRT) have enrolled a select group of patients, with few patients in subgroups such as right bundle-branch block (RBBB). Analysis of population-based outcomes provides a method to identify real-world predictors of CRT outcomes.

Methods and Results—

Medicare Implantable Cardioverter-Defibrillator Registry (2005 to 2006) data were merged with patient outcomes data. Cox proportional-hazards models assessed death and death/heart failure hospitalization outcomes in patients with CRT and an implantable cardioverter-defibrillator (CRT-D). The 14 946 registry patients with CRT-D (median follow-up, 40 months) had 1-year, 3-year, and overall mortality rates of 12%, 32%, and 37%, respectively. New York Heart Association class IV heart failure status (1-year hazard ratio [HR], 2.23; 3-year HR, 1.98;
P
<0.001) and age ≥80 years (1-year HR, 1.74; 3-year HR, 1.75;
P
<0.001) were associated with increased mortality both early and late after CRT-D. RBBB (1-year HR, 1.44; 3-year HR, 1.37;
P
<0.001) and ischemic cardiomyopathy (1-year HR, 1.39; 3-year HR, 1.44;
P
<0.001) were the next strongest adjusted predictors of both early and late mortality. RBBB and ischemic cardiomyopathy together had twice the adjusted hazard for death (HR, 1.99;
P
<0.001) as left BBB and nonischemic cardiomyopathy. QRS duration of at least 150 ms predicted more favorable outcomes in left BBB but had no impact in RBBB. A secondary analysis showed lower hazards for CRT-D compared with standard implantable cardioverter-defibrillators in left BBB compared with RBBB.

Conclusions—

In Medicare patients, RBBB, ischemic cardiomyopathy, New York Heart Association class IV status, and advanced age were powerful adjusted predictors of poor outcome after CRT-D. Real-world mortality rates 3 to 4 years after CRT-D appear higher than previously recognized.