bluuebunny/crossref_metadata_2025 huggingface dataset:
The experience of being diagnosed with hypertrophic cardiomyopathy through family screening in childhood and adolescence
Authors: Bratt Ewa-Lena , Sparud-Lundin Carina , Östman-Smith Ingegerd , Axelsson Åsa B.
Published: January 2012

Aim

To describe the experiences of children and adolescents being screened positive for hypertrophic cardiomyopathy and how this impacts their daily life.

Background

Hypertrophic cardiomyopathy is a hereditary disease and the most common medical cause of sudden death in childhood and adolescence. This is the reason for recommending screening in children with an affected first-degree relative. A diagnosis of hypertrophic cardiomyopathy implies lifestyle modifications, restrictions that may bring profound changes to the daily life of the affected individual.

Design

This is a descriptive qualitative interview study.

Methods

We interviewed 13 asymptomatic children or adolescents diagnosed with hypertrophic cardiomyopathy through family screening 12–24 months after the diagnosis. Analysis was conducted with qualitative content analysis.

Results

Children described an involuntary change, which affected their daily life with limitations and restrictions in life, both in the individual and social context. Lifestyle recommendations had the most severe impact on daily life and affected their social context. They tried to navigate in a world with new references, and after reorientation they felt hope and had faith in the future.

Conclusions

Children diagnosed with hypertrophic cardiomyopathy through family screening went through an involuntary change resulting in limitations and restrictions in life. This study indicates that there is a need for support and that healthcare professionals have to consider the specific needs in these families. Our findings thus give guidance in how best to improve support to the patients and their family. Diagnosis in asymptomatic children should be accompanied by ideally multi-professional follow-up, focusing not only on medical issues.
MUST THE LAW BE CAPABLE OF POSSESSING AUTHORITY?
Authors: Smith Dale
Published: January 2012

Joseph Raz famously argues that given that the law necessarily claims authority and given the account of authority he provides, exclusive legal positivism is the only tenable theory of law. In this article, I contend that even if one accepts that the law necessarily claims authority and that Raz's account of authority is correct, it does not follow that exclusive legal positivism is the only tenable theory of law. This is because even if the law necessarily claims authority, it need not be capable of satisfying the requirements for possessing authority laid down by the correct account of authority. Thus, even if exclusive legal positivism is the only theory of law according to which the law can satisfy those requirements, this does not show that exclusive legal positivism is correct.
Changes in Neuropsychological and Behavioral Functioning in Children with and without Obstructive Sleep Apnea Following Tonsillectomy
Authors: Giordani Bruno , Hodges Elise K. , Guire Kenneth E. , Ruzicka Deborah L. , Dillon James E. , Weatherly Robert A. , Garetz Susan L. , Chervin Ronald D.
Published: January 2012

The most common treatment for sleep disordered breathing (SDB) is adenotonsillectomy (AT). Following AT, SDB resolves in most cases, and gains in cognitive and behavior scores are consistently reported, although persistent neuropsychological deficits or further declines also have been noted. This study presents results of the comprehensive 1-year follow-up neuropsychological examinations for children in the Washtenaw County Adenotonsillectomy Cohort I (95% return rate). After adjusting for normal developmental and practice-effect related changes in control children, significant improvements 1 year following AT were noted in polysomnography and sleepiness, as well as parental reports of behavior, although cognitive outcomes were mixed. Children undergoing AT with and without polysomnography-confirmed obstructive sleep apnea improved across a range of academic achievement measures, a measure of delayed visual recall, short-term attention/working memory, and executive functioning, along with parental ratings of behavior. On the other hand, measures of verbal abstraction ability, arithmetic calculations, visual and verbal learning, verbal delayed recall, sustained attention, and another measure of visual delayed recall demonstrated declines in ability, while other measures did not improve over time. These findings call into question the expectation that AT resolves most or all behavioral and cognitive difficulties in children with clinical, office-based diagnoses of SDB. (JINS, 2012,18, 212–222)
Performance Monitoring and Cognitive Control in Individuals with Mild Traumatic Brain Injury
Authors: Larson Michael J. , Clayson Peter E. , Farrer Thomas J.
Published: January 2012

Literature suggests that individuals with mild traumatic brain injury (mTBI) show subtle abnormalities in the cognitive control process of performance monitoring. The neural bases of performance monitoring can be measured using the error-related negaitivity (ERN) and post-error positivity (Pe) components of the scalp-recorded event-related potential (ERP). Thirty-six individuals with mTBI and 46 demographically similar controls completed a modified color-naming Stroop task while ERPs were recorded. Separate repeated-measures analyses of variance were used to examine the behavioral (response times [RT] and error rates) and ERP (ERN and Pe amplitudes) indices of performance monitoring. Both groups showed slower RTs and increased error rates on incongruent trials relative to congruent trials. Likewise, both groups showed more negative ERN and more positive Pe amplitude to error trials relative to correct trials. Notably, there were no significant main effects or interactions of group for behavioral and ERP measures. Subgroup and correlational analyses with post-concussive symptoms and indices of injury severity were also not significant. Findings suggest comparable performance to non-injured individuals in some aspects of cognitive control in this sample. Neuropsychological implications and comparison with other cognitive control component processes in individuals with TBI are provided. (JINS, 2012, 18, 323–333)
Predictive modelling of interventions to improve iodine intake in New Zealand
Authors: Schiess Sonja , Cressey Peter J , Thomson Barbara M
Published: January 2012

Objective

The potential effects of four interventions to improve iodine intakes of six New Zealand population groups are assessed.

Design

A model was developed to estimate iodine intake when (i) bread is manufactured with or without iodized salt, (ii) recommended foods are consumed to augment iodine intake, (iii) iodine supplementation as recommended for pregnant women is taken and (iv) the level of iodization for use in bread manufacture is doubled from 25–65 mg to 100 mg iodine/kg salt.

Setting

New Zealanders have low and decreasing iodine intakes and low iodine status. Predictive modelling is a useful tool to assess the likely impact, and potential risk, of nutrition interventions.

Subjects

Food consumption information was sourced from 24 h diet recall records for 4576 New Zealanders aged over 5 years.

Results

Most consumers (73–100 %) are predicted to achieve an adequate iodine intake when salt iodized at 25–65 mg iodine/kg salt is used in bread manufacture, except in pregnant females of whom 37 % are likely to meet the estimated average requirement. Current dietary advice to achieve estimated average requirements is challenging for some consumers. Pregnant women are predicted to achieve adequate but not excessive iodine intakes when 150 μg of supplemental iodine is taken daily, assuming iodized salt in bread.

Conclusions

The manufacture of bread with iodized salt and supplemental iodine for pregnant women are predicted to be effective interventions to lift iodine intakes in New Zealand. Current estimations of iodine intake will be improved with information on discretionary salt and supplemental iodine usage.
Dynamics of knowledge in DeLP through Argument Theory Change
Authors: MOGUILLANSKY MARTÍN O. , ROTSTEIN NICOLÁS D. , FALAPPA MARCELO A. , GARCÍA ALEJANDRO J. , SIMARI GUILLERMO R.
Published: January 2012

This article is devoted to the study of methods to change defeasible logic programs (de.l.p.s) which are the knowledge bases used by the Defeasible Logic Programming (DeLP) interpreter. DeLP is an argumentation formalism that allows to reason over potentially inconsistent de.l.p.s. Argument Theory Change (ATC) studies certain aspects of belief revision in order to make them suitable for abstract argumentation systems. In this article, abstract arguments are rendered concrete by using the particular rule-based defeasible logic adopted by DeLP. The objective of our proposal is to define prioritized argument revision operators à la ATC for de.l.p.s, in such a way that the newly inserted argument ends up undefeated after the revision, thus warranting its conclusion. In order to ensure this warrant, the de.l.p. has to be changed in concordance with a minimal change principle. To this end, we discuss different minimal change criteria that could be adopted. Finally, an algorithm is presented, implementing the argument revision operations.
Consistent query answering via ASP from different perspectives: Theory and practice
Authors: MANNA MARCO , RICCA FRANCESCO , TERRACINA GIORGIO
Published: January 2012

A data integration system provides transparent access to different data sources by suitably combining their data, and providing the user with a unified view of them, called global schema. However, source data are generally not under the control of the data integration process; thus, integrated data may violate global integrity constraints even in the presence of locally consistent data sources. In this scenario, it may be anyway interesting to retrieve as much consistent information as possible. The process of answering user queries under global constraint violations is called consistent query answering (CQA). Several notions of CQA have been proposed, e.g., depending on whether integrated information is assumed to be sound, complete, exact, or a variant of them. This paper provides a contribution in this setting: it uniforms solutions coming from different perspectives under a common Answer-Set Programming (ASP)-based core, and provides query-driven optimizations designed for isolating and eliminating inefficiencies of the general approach for computing consistent answers. Moreover, the paper introduces some new theoretical results enriching existing knowledge on the decidability and complexity of the considered problems. The effectiveness of the approach is evidenced by experimental results.
Institutional reversals and economic growth: Palestine 1516–1948
Authors: SCHEIN ANDREW
Published: January 2012

This study examines the type and quality of institutions in Palestine and the correlation between the institutions and economic growth in Palestine from 1516 to 1948. Initially in the 16th century, with the Ottoman conquest of the area, institutions in Palestine involvedde factoprivate user-rights. The level of expropriation by elites was low, and this enabled the people to develop the lands that they had acquired the right to cultivate. In the 17th and 18th centuries, with the exception of the Galilee in the middle of the 18th century, institutions became extractive due to tax farming, rapacious governors and Bedouin raids. From the middle of the 19th century until 1948, there was a second reversal back to private property institutions, first slowly until the First World War, and then more rapidly under the British Mandate after the First World War. When there were private property institutions the economy prospered, while when there were extractive institutions, the economy stagnated.
Mechanisms of an extraordinary East Asian summer monsoon event in July 2011
Authors: Seo Kyong‐Hwan , Son Jun‐Hyeok , Lee Seung‐Eon , Tomita Tomohiko , Park Hyo‐Seok
Published: January 2012

Previous studies have demonstrated that the strong East Asian summer monsoon results mainly from the westward intensification of the North Pacific subtropical high (NPSH), or equivalently, the enhancement of the western North Pacific subtropical high. However, during early July in 2011 a strong southerly or southeasterly moist flow gave rise to a large amount of precipitation over southwestern Japan and Korea and anomalous dry conditions over central China because of the extraordinary intensification of the NPSH to the north. The formation of the anomalous high that occurred to the east of central Japan during early July is very rare, and its physical mechanisms are investigated in this study. The regressed circulation anomalies and wave‐activity flux vectors for July 2011 and data from the previous 32 years show that two teleconnection patterns due to Rossby wave trains are the most important mechanisms: Rossby wave propagation from the eastern North Atlantic and western Europe to East Asia following the North Eurasian jet and East Asian jet in the upper level, and northward propagation of Rossby waves forced by diabatic heating over the western North Pacific (WNP) region in the lower level. This simultaneous forcing of a significant negative phase of the summertime North Atlantic Oscillation in the higher latitudes and enhanced diabatic heating over the subtropical WNP is found to be the cause of the abnormal development of the anomalous high to the east of central Japan, resulting in extremely wet conditions in Korea and southern Japan and dry conditions in southern China.
Very low frequency earthquakes along the Ryukyu subduction zone
Authors: Ando Masataka , Tu Yoko , Kumagai Hiroyuki , Yamanaka Yoshiko , Lin Cheng‐Horng
Published: January 2012

A total of 1314 very low frequency earthquakes (VLFEs) were identified along the Ryukyu trench from seismograms recorded at broadband networks in Japan (F‐net) and Taiwan (BATS) in 2007. The spectra of typical VLFEs have peak frequencies between 0.02 to 0.1 Hz. Among those, waveforms from 120 VLFEs were inverted to obtain their centoroid moment tensor (CMT) solutions and locations using an examination grid to minimize a residual between the observed and synthetic waveforms within an area of 11° × 14° in latitude and longitude and at depths of 0 to 60 km. Most of the VLFEs occur on shallow thrust faults that are distributed along the Ryukyu trench, which are similar to those earthquakes found in Honshu and Hokkaido, Japan. The locations and mechanisms of VLFEs may be indicative of coupled regions within the accretionary prism or at the plate interface; this study highlights the need for further investigation of the Ryukyu trench to identify coupled regions within it.
Constraints on fault and lithosphere rheology from the coseismic slip and postseismic afterslip of the 2006 Mw7.0 Mozambique earthquake
Authors: Copley Alex , Hollingsworth James , Bergman Eric
Published: January 2012

The 2006 Mw7.0 Mozambique (Machaze) normal‐faulting earthquake ruptured an unusually steeply dipping fault plane (∼75°). The amount of slip in the earthquake decreased from depths of ∼10 km toward the surface, and this shallow slip deficit was at least partly recovered by postseismic afterslip on the shallow part of the fault plane. An adjacent normal fault segment slipped postseismically (and possibly also co‐seismically) at shallow depths with a large strike‐slip component, in response to the stresses generated by slip on the main earthquake fault plane. Our observations suggest that the fault zone behaves in a stick‐slip manner in the crystalline basement, and that where it cuts the sedimentary layer the coseismic rupture was partially arrested and there was significant postseismic creep. We discuss the effects of such behavior on the large‐scale tectonics of continental regions, and on the assessment of seismic hazard on similar fault systems. The steep dip of the fault suggests the re‐activation of a preexisting structure with a coefficient of friction at least ∼25–45% lower than that on optimally oriented planes, and analysis of the deformation following an aftershock indicates that the value of the parameter ‘a’ that describes the rate‐dependence of fault friction lies in the range 1 × 10−3–2 × 10−2. The lack of long‐wavelength postseismic relaxation suggests viscosities in the ductile lithosphere of greater than ∼2 × 1019 Pa s, and an examination of the tectonic geomorphology in the region identifies ways in which similar fault systems can be identified before they rupture in future earthquakes.
Effect of emissions inventory versus climate model resolution on radiative forcing and precipitation over the continental United States
Authors: Owen R. C. , Steiner A. L.
Published: January 2012

We evaluate the impact of anthropogenic emission inventory and climate model grid resolution on aerosol concentrations and black direct aerosol top of atmosphere forcing. Anthropogenic aerosol concentrations of sulfate, black carbon (BC), and organic carbon (OC) are simulated using a high‐resolution (25 km) regional climate model (RegCM) with (1) the 2000 1° × 1° EDGAR inventory and (2) the 1999 4 km U.S. Environmental Protection Agency (EPA) National Emissions Inventory. A third 60 km EPA simulation tests the effect of climate model resolution. Simulated SO2 and SO42− concentrations from the 25 km simulations agree with observations in DJF, but JJA modeled SO2 is high and SO42− is low by a factor of 2–3 suggesting incomplete sulfate conversion in the model. Simulated BC and OC concentrations are lower than observations, and sensitivity tests suggest the inventories are missing carbonaceous sources. Total aerosol optical depth (AOD) is greater than observations in DJF and lower in JJA, confirming an underestimation of aerosols during summertime. Derived top of atmosphere radiative forcing has a maximum JJA decrease of 7, 8, and 10 W/m2 in the EDGAR, EPA 25 km, and EPA 60 km simulations, respectively. Generally, the 60 km simulations improve measured‐modeled aerosol agreement due to reduced precipitation and wet deposition in the 60 km simulation. Comparisons with observations indicate that total precipitation in the 60 km simulation is closer to observations. Thus, aerosol forcings from a regional model may be equally sensitive to resolution and emissions inventory due to the parameterization of large‐scale precipitation and wet removal processes.
Initiation of the Southern Elsinore Fault at ∼1.2 Ma: Evidence from the Fish Creek–Vallecito Basin, southern California
Authors: Dorsey Rebecca J. , Axen Gary J. , Peryam Thomas C. , Kairouz Mary E.
Published: January 2012

Strike‐slip faults west of the San Andreas fault (SAF) accommodate more than half of the modern Pacific–North America plate motion in southern California, yet their age, kinematic evolution and long‐term slip rates are incompletely understood. The southern Elsinore fault is part of this zone and occupies the boundary between Mesozoic crystalline rocks of the Peninsular Ranges and Late Cenozoic sedimentary rocks of the Salton Trough depocenter. The Fish Creek–Vallecito Basin, a recently inverted western sub‐basin of the Salton Trough, contains a thick succession of Plio‐Pleistocene sedimentary rocks that preserve a record of crustal subsidence and uplift in response to evolving tectonic controls. Deposits older than ∼1.2 Ma accumulated during transtension and subsidence in the hanging wall of the low‐angle West Salton detachment fault. A fanning‐dip interval high in the section, dated at 1.2–1.0 Ma, accumulated during tilting caused by earliest motion on the Elsinore and Earthquake Valley faults. Total offset of 1–2 km yields a lifetime slip rate of about 1–2 mm/yr for the southern Elsinore fault, similar to a late Pleistocene rate in the Coyote Mountains but slower than published estimates for the northern Elsinore fault. This difference likely results from long‐term transfer of slip from the northern Elsinore fault to the San Felipe and San Jacinto fault zones farther east. Initiation of the Elsinore fault at 1.2 Ma coincides with a major tectonic reorganization that terminated slip on the detachment fault and formed the modern network of strike‐slip faults west of the SAF.
Combining PET Biodistribution and Equilibrium Dialysis Assays to Assess the Free Brain Concentration and BBB Transport of CNS Drugs
Authors: Gunn Roger N , Summerfield Scott G , Salinas Cristian A , Read Kevin D , Guo Qi , Searle Graham E , Parker Christine A , Jeffrey Phil , Laruelle Marc
Published: January 2012

The passage of drugs in and out of the brain is controlled by the blood—brain barrier (BBB), typically, using either passive diffusion across a concentration gradient or active transport via a protein carrier. In-vitro and preclinical measurements of BBB penetration do not always accurately predict the in-vivo situation in humans. Thus, the ability to assay the concentration of novel drug candidates in the human brain in vivo provides valuable information for derisking of candidate molecules early in drug development. Here, positron emission tomography (PET) measurements are combined with in-vitro equilibrium dialysis assays to enable assessment of transport and estimation of the free brain concentration in vivo. The PET and equilibrium dialysis data were obtained for 36 compounds in the pig. Predicted P-glycoprotein (P-gp) status of the compounds was consistent with the PET/equilibrium dialysis results. In particular, Loperamide, a well-known P-gp substrate, exhibited a significant concentration gradient consistent with active efflux and after inhibition of the P-gp process the gradient was removed. The ability to measure the free brain concentration and assess transport of novel compounds in the human brain with combined PET and equilibrium dialysis assays can be a useful tool in central nervous system (CNS) drug development.
Structural and functional validation of Microsystin synthetases
Authors: Sanmukh Swapnil , Paunikar Waman
Published: January 2012

The structure and function prediction for the Microsystin synthetases from Microsystis aerogenosa (LNSAMB) were carried out for verifying the authenticity of the sequenced genes. The genes for Microsystin synthetases (mcyA, mcyB, mcyD and mcyE,), were predicted by the application of computational methods and Bioinformatics web tools. The probable function prediction for the proteins was done by using Bioinformatics web tools like CDD-BLAST, INTERPROSCAN, PFAM and COGs by searching protein databases for the presence of conserved domains. While tertiary structures were constructed using PS2 Server- Protein Structure Prediction server. This study revealed structural and functional validation of sequenced genes.
The non-steroidal anti-inflammatory drug indomethacin activates the eIF2α kinase PKR, causing a translational block in human colorectal cancer cells
Authors: Brunelli Claudia , Amici Carla , Angelini Mara , Fracassi Chiara , Belardo Giuseppe , Santoro M. Gabriella
Published: January 2012

The NSAID (non-steroidal anti-inflammatory drug) indomethacin, a cyclo-oxygenase-1 and -2 inhibitor with anti-inflammatory and analgesic properties, is known to possess anticancer activity against CRC (colorectal cancer) and other malignancies in humans; however, the mechanism underlying the anticancer action remains elusive. In the present study we show that indomethacin selectively activates the dsRNA (double-stranded RNA)-dependent protein kinase PKR in a cyclo-oxygenase-independent manner, causing rapid phosphorylation of eIF2α (the α-subunit of eukaryotic translation initiation factor 2) and inhibiting protein synthesis in colorectal carcinoma and other types of cancer cells. The PKR-mediated translational block was followed by inhibition of CRC cell proliferation and apoptosis induction. Indomethacin did not affect the activity of the eIF2α kinases PERK (PKR-like endoplasmic reticulum-resident kinase), GCN2 (general control non-derepressible-2) and HRI (haem-regulated inhibitor kinase), and induced eIF2α phosphorylation in PERK-knockout and GCN2-knockout cells, but not in PKR-knockout cells or in human PKR-silenced CRC cells, identifying PKR as a selective target for indomethacin-induced translational inhibition. The fact that indomethacin induced PKR activity in vitro, an effect reversed by the PKR inhibitor 2-aminopurine, suggests a direct effect of the drug in kinase activation. The results of the present study identify PKR as a novel target of indomethacin, suggesting new scenarios on the molecular mechanisms underlying the pleiotropic activity of this traditional NSAID.
First identification of small-molecule inhibitors of Pontin by combining virtual screening and enzymatic assay
Authors: Elkaim Judith , Castroviejo Michel , Bennani Driss , Taouji Said , Allain Nathalie , Laguerre Michel , Rosenbaum Jean , Dessolin Jean , Lestienne Patrick
Published: January 2012

The human protein Pontin, which belongs to the AAA+ (ATPases associated with various cellular activities) family, is overexpressed in several cancers and its silencing in vitro leads to tumour cell growth arrest and apoptosis, making it a good target for cancer therapy. In particular, high levels of expression were found in hepatic tumours for which the therapeutic arsenal is rather limited. The three-dimensional structure of Pontin has been resolved previously, revealing a hexameric assembly with one ADP molecule co-crystallized in each subunit. Using Vina, DrugScore and Xscore, structure-based virtual screening of 2200 commercial molecules was conducted into the ATP-binding site formed by a dimer of Pontin in order to prioritize the best candidates. Complementary to the in silico screening, a versatile and sensitive colorimetric assay was set up to measure the disruption of the ATPase activity of Pontin. This assay allowed the determination of inhibition curves for more than 20 top-scoring compounds, resulting in the identification of four ligands presenting an inhibition constant in the micromolar concentration range. Three of them inhibited tumour cell proliferation. The association of virtual screening and experimental assay thus proved successful for the discovery of the first small-molecule inhibitors of Pontin.
ROCKII Ser1366 phosphorylation reflects the activation status
Authors: Chuang Hsiang-Hao , Yang Chih-Hsuan , Tsay Yeou-Guang , Hsu Chih-Yi , Tseng Ling-Ming , Chang Zee-Fen , Lee Hsiao-Hui
Published: January 2012

ROCK (Rho-associated protein kinase), a downstream effector of RhoA, plays an important role in many cellular processes. Accumulating evidence has shown the involvement of ROCK activation in the pathogenesis of many diseases. However, a reagent capable of detecting ROCK activation directly is lacking. In the present study, we show autophosphorylation of ROCKII in an in vitro kinase reaction. The phosphorylation sites were identified by MS, and the major phosphorylation site was found to be at the highly conserved residue Ser1366. A phospho-specific antibody was generated that can specifically recognize ROCKII Ser1366 phosphorylation. We found that the extent of Ser1366 phosphorylation of endogenous ROCKII is correlated with that of myosin light chain phosphorylation in cells in response to RhoA stimulation, showing that Ser1366 phosphorylation reflects its kinase activity. In addition, ROCKII Ser1366 phosphorylation could be detected in human breast tumours by immunohistochemical staining. The present study provides a new approach for revealing the ROCKII activation status by probing ROCKII Ser1366 phosphorylation directly in cells or tissues.
Transforming growth factor β1 represses proximal tubular cell microRNA-192 expression through decreased hepatocyte nuclear factor DNA binding
Authors: Jenkins Robert H. , Martin John , Phillips Aled O. , Bowen Timothy , Fraser Donald J.
Published: January 2012

miR (microRNA)-192 plays key roles in renal pathological and physiological responses, by repressing targets including Zeb1, Zeb2 and Wnk1. In the present study, we have assessed the regulation of miR-192 expression. We found that TGF-β1 (transforming growth factor β1) down-regulates miR-192 and miR-194, co-transcribed in the shared precursor pri-miR (primary miR transcript)-192/194. Luciferase reporter analysis showed constitutive promoter activity within nucleotides +21 to −223. We identified HNF (hepatocyte nuclear factor) and p53 binding sites within this region that were required for constitutive promoter activity, which was decreased by TGF-β1 through an Alk5-dependent mechanism. TGF-β1 treatment decreased HNF binding to the miR-194-2/192 promoter, whereas knockdown of HNF-1 inhibited mature miR-192 and miR-194 expression. miR-192, miR-194 and HNF expression were restricted to a defined subset of human tissues including kidney, small intestine, colon and liver. Our results from the present study identify co-ordinated regulation of miR-192 and miR-194, with binding of HNF and p53 transcription factors necessary for activation of transcription, and TGF-β1-mediated repression through decreased HNF binding to its cognate promoter element.
Role of syndecan‐4 side chains in turkey satellite cell apoptosis and focal adhesion formation
Authors: Song Yan , McFarland Douglas C. , Velleman Sandra G.
Published: January 2012

S4 (syndecan‐4) is a cell membrane heparan sulfate proteoglycan that functions in muscle growth and development. It is composed of a central core protein and two types of side chains: GAGs (glycosaminoglycans) and N‐glycosylated (N‐linked glycosylated) chains. The N‐glycosylated chains and GAG chains are required for S4 to regulate turkey myogenic satellite cell proliferation. The objective of the current study was to determine whether the S4 side chains regulate cell proliferation through muscle cell focal adhesion formation and apoptosis. S4 mutants with only one or without any N‐glycosylated chains attached to the core protein with or without GAG chains were generated to study the function of N‐glycosylated chains and the interaction between N‐glycosylated chains and GAG chains. The wild‐type S4 and all of the S4 side chain mutants were transfected into turkey myogenic satellite cells. Cell apoptosis and focal adhesion formation were measured, and PKCα (protein kinase Cα) cell membrane localization was investigated. S4 increased FAK (focal adhesion kinase) activity and the deletion of the side chains decreased this effect. S4 and the S4 mutants had no effect on β1‐integrin expression, but increased the cell membrane localization of β1‐integrin and PKCα. Furthermore, cell apoptosis and vinculin containing focal adhesions were not affected by S4 and its mutants. The results suggest that S4 and its side chains play important roles in regulating FAK activity, and PKCα and β1‐integrin cell membrane localization, but not cell apoptosis and vinculin‐containing focal adhesion formation.
Maternal modulation of novelty effects on physical development
Authors: Tang Akaysha C. , Yang Zhen , Reeb-Sutherland Bethany C. , Romeo Russell D. , McEwen Bruce S.
Published: January 2012

Familiarity to the mother and the novelty afforded by the postnatal environment are two contrasting sources of neonatal influence. One hypothesis regarding their relationship is the maternal modulation hypothesis, which predicts that the same neonatal stimulation may have different effects depending on the maternal context. Here we tested this hypothesis using physical development, indexed by body weight, as an endpoint and found that, among offspring of mothers with a high initial swim-stress–induced corticosterone (CORT) response, neonatal novelty exposure induced an enhancement in early growth, and among offspring with mothers of a low initial CORT response, the same neonatal stimulation induced an impairment. At an older age, a novelty-induced increase in body weight was also found among offspring of mothers with high postnatal care reliability and a novelty-induced reduction found among offspring of mothers with low care reliability. These results support a maternal modulation of early stimulation effects on physical development and demonstrate that the maternal influence originates from multiple instead of any singular sources. These results (
i
) significantly extend the findings of maternal modulation from the domain of cognitive development to the domain of physical development; (
ii
) offer a unifying explanation for a previously inconsistent literature regarding early stimulation effects on body weight; and (
iii
) highlight the notion that the early experience effect involves no causal primacy but higher order interactions among the initial triggering events and subsequent events involving a multitude of maternal and nonmaternal influences.
Therapeutic antimicrobial peptides may compromise natural immunity
Authors: Habets Michelle G. J. L. , Brockhurst Michael A.
Published: January 2012

Antimicrobial peptides (AMPs) have been proposed as a promising new class of antimicrobials despite warnings that therapeutic use could drive the evolution of pathogens resistant to our own immunity peptides. Using experimental evolution, we demonstrate that
Staphylococcus aureus
rapidly evolved resistance to pexiganan, a drug-candidate for diabetic leg ulcer infections. Evolved resistance was costly in terms of impaired growth rate, but costs-of-resistance were completely ameliorated by compensatory adaptation. Crucially, we show that, in some populations, experimentally evolved resistance to pexiganan provided
S. aureus
with cross-resistance to human-neutrophil-defensin-1, a key component of the innate immune response to infection. This unintended consequence of therapeutic use could drastically undermine our innate immune system's ability to control and clear microbial infections. Our results therefore highlight grave potential risks of AMP therapies, with implications for their development.
Bone tissue reactions to biomimetic ion-substituted apatite surfaces on titanium implants
Authors: Ballo Ahmed M. , Xia Wei , Palmquist Anders , Lindahl Carl , Emanuelsson Lena , Lausmaa Jukka , Engqvist Håkan , Thomsen Peter
Published: January 2012

The aim of this study was to evaluate the bone tissue response to strontium- and silicon-substituted apatite (Sr-HA and Si-HA) modified titanium (Ti) implants. Sr-HA, Si-HA and HA were grown on thermally oxidized Ti implants by a biomimetic process. Oxidized implants were used as controls. Surface properties, i.e. chemical composition, surface thickness, morphology/pore characteristics, crystal structure and roughness, were characterized with various analytical techniques. The implants were inserted in rat tibiae and block biopsies were prepared for histology, histomorphometry and scanning electron microscopy analysis. Histologically, new bone formed on all implant surfaces. The bone was deposited directly onto the Sr-HA and Si-HA implants without any intervening soft tissue. The statistical analysis showed significant higher amount of bone–implant contact (BIC) for the Si-doped HA modification (P= 0.030), whereas significant higher bone area (BA) for the Sr-doped HA modification (P= 0.034), when compared with the non-doped HA modification. The differences were most pronounced at the early time point. The healing time had a significant impact for both BA and BIC (P< 0.001). The present results show that biomimetically prepared Si-HA and Sr-HA on Ti implants provided bioactivity and promoted early bone formation.
Key canopy traits drive forest productivity
Authors: Reich Peter B.
Published: January 2012

Quantifying the mechanistic links between carbon fluxes and forest canopy attributes will advance understanding of leaf-to-ecosystem scaling and its potential application to assessing terrestrial ecosystem metabolism. Important advances have been made, but prior studies that related carbon fluxes to multiple canopy traits are scarce. Herein, presenting data for 128 cold temperate and boreal forests across a regional gradient of 600 km and 5.4°C (from 2.4°C to 7.8°C) in mean annual temperature, I show that stand-scale productivity is a function of the capacity to harvest light (represented by leaf area index, LAI), and to biochemically fix carbon (represented by canopy nitrogen concentration, %N). In combination, LAI and canopy %N explain greater than 75 per cent of variation in above-ground net primary productivity among forests, expressed per year or per day of growing season. After accounting for growing season length and climate effects, less than 10 per cent of the variance remained unexplained. These results mirror similar relations of leaf-scale and canopy-scale (eddy covariance) maximum photosynthetic rates to LAI and %N. Collectively, these findings indicate that canopy structure and chemistry translate from instantaneous physiology to annual carbon fluxes. Given the increasing capacity to remotely sense canopy LAI, %N and phenology, these results support the idea that physiologically based scaling relations can be useful tools for global modelling.
Reduced metabolic rate and oxygen radicals production in stored insect sperm
Authors: Ribou Anne-Cécile , Reinhardt Klaus
Published: January 2012

Females of internally fertilizing species can significantly extend sperm lifespan and functionality during sperm storage. The mechanisms for such delayed cellular senescence remain unknown. Here, we apply current hypotheses of cellular senescence developed for diploid cells to sperm cells, and empirically test opposing predictions on the relationship between sperm metabolic rate and oxygen radical production in an insect model, the cricket
Gryllus bimaculatus
. Using time-resolved microfluorimetry, we found a negative correlation between metabolic rate (proportion of protein-bound NAD[P]H) and
in situ
intracellular oxygen radicals production in freshly ejaculated sperm. In contrast, sperm stored by females for periods of 1 h to 26 days showed a positive correlation between metabolic rate and oxygen radicals production. At the same time, stored sperm showed a 37 per cent reduced metabolic rate, and 42 per cent reduced reactive oxygen species (ROS) production, compared with freshly ejaculated sperm. Rank differences between males in ROS production and metabolic rate observed in ejaculated sperm did not predict rank differences in stored sperm. Our method of simultaneously measuring ROS production and metabolic rate of the same sample has the advantage of providing data that are independent of sperm density and any extracellular antioxidants that are proteins. Our method also excludes effects owing to accumulated hydrogen peroxide. Our results unify aspects of competing theories of cellular ageing and suggest that reducing metabolic rate may be an important means of extending stored sperm lifespan and functionality in crickets. Our data also provide a possible explanation for why traits of ejaculates sampled from the male may be rather poor predictors of paternity in sexual selection studies and likelihood of pregnancy in reproductive medicine.
Cooperative breeding and monogamy in mammalian societies
Authors: Lukas Dieter , Clutton-Brock Tim
Published: January 2012

Comparative studies of social insects and birds show that the evolution of cooperative and eusocial breeding systems has been confined to species where females mate completely or almost exclusively with a single male, indicating that high levels of average kinship between group members are necessary for the evolution of reproductive altruism. In this paper, we show that in mammals, the evolution of cooperative breeding has been restricted to socially monogamous species which currently represent 5 per cent of all mammalian species. Since extra-pair paternity is relatively uncommon in socially monogamous and cooperatively breeding mammals, our analyses support the suggestion that high levels of average kinship between group members have played an important role in the evolution of cooperative breeding in non-human mammals, as well as in birds and insects.
MASTR directs MyoD-dependent satellite cell differentiation during skeletal muscle regeneration
Authors: Mokalled Mayssa H. , Johnson Aaron N. , Creemers Esther E. , Olson Eric N.
Published: January 2012

In response to skeletal muscle injury, satellite cells, which function as a myogenic stem cell population, become activated, expand through proliferation, and ultimately fuse with each other and with damaged myofibers to promote muscle regeneration. Here, we show that members of the Myocardin family of transcriptional coactivators, MASTR and MRTF-A, are up-regulated in satellite cells in response to skeletal muscle injury and muscular dystrophy. Global and satellite cell-specific deletion of MASTR in mice impairs skeletal muscle regeneration. This impairment is substantially greater when MRTF-A is also deleted and is due to aberrant differentiation and excessive proliferation of satellite cells. These abnormalities mimic those associated with genetic deletion of MyoD, a master regulator of myogenesis, which is down-regulated in the absence of MASTR and MRTF-A. Consistent with an essential role of MASTR in transcriptional regulation of MyoD expression, MASTR activates a muscle-specific postnatal MyoD enhancer through associations with MEF2 and members of the Myocardin family. Our results provide new insights into the genetic circuitry of muscle regeneration and identify MASTR as a central regulator of this process.
Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia
Authors: Glaser Stefan P. , Lee Erinna F. , Trounson Evelyn , Bouillet Philippe , Wei Andrew , Fairlie W. Douglas , Izon David J. , Zuber Johannes , Rappaport Amy R. , Herold Marco J. , Alexander Warren S. , Lowe Scott W. , Robb Lorraine , Strasser Andreas
Published: January 2012

Acute myeloid leukemia (AML) frequently relapses after initial treatment. Drug resistance in AML has been attributed to high levels of the anti-apoptotic Bcl-2 family members Bcl-xL and Mcl-1. Here we report that removal of Mcl-1, but not loss or pharmacological blockade of Bcl-xL, Bcl-2, or Bcl-w, caused the death of transformed AML and could cure disease in AML-afflicted mice. Enforced expression of selective inhibitors of prosurvival Bcl-2 family members revealed that Mcl-1 is critical for survival of human AML cells. Thus, targeting of Mcl-1 or regulators of its expression may be a useful strategy for the treatment of AML.
A zipcode unzipped: Figure 1.
Authors: Doyle Michael , Kiebler Michael A.
Published: January 2012

RNA-binding proteins (RBPs) exert many roles in the post-transcriptional regulation of gene expression in eukaryotic cells. However, our understanding of how they recognize their target RNAs in vivo remains limited. In the January 1, 2012, issue of Genes & Development, Patel and colleagues (p. 43–53) provide detailed mechanistic insights into how one of the best-studied RBPs, zipcode-binding protein 1 (ZBP1), recognizes a bipartite RNA sequence element within the β-actin mRNA.
Robustness to thermal variability differs along a latitudinal gradient in zooplankton communities
Authors: Tuck Constance , Romanuk Tamara N.
Published: January 2012

Determining how thermal variability will affect the structure, stability, and function of ecological communities is becoming increasingly important as global warming is predicted to affect not only average temperatures but also increase the frequency of long runs of high temperatures. Latitudinal differences in the responses of ecological communities to changes in their thermal regimes have also been predicted based on adaptations over evolutionary time to different thermal environments. We conducted an experiment to determine whether variability in temperature leads to consistent changes in community structure, temporal dynamics, and ecosystem functioning in laboratory analogues of natural freshwater supralittoral rock pool communities inhabited by meiofauna and zooplankton collected from sub‐Arctic, temperate, and tropical regions. Thermal variability of +4 °C around mean temperature led to increased extinction frequency, decreases in consumer abundance, increases in temporal variability of consumer abundance, and shifts from predominately negative interactions observed under constant temperature to positive interactions in the temperate and tropical communities but not in the sub‐Arctic communities. That sub‐Arctic zooplankton communities may be more robust to thermal variability than temperate or tropical communities’ supports recent studies on macrophysiological adaptations of species along latitudinal gradients and suggests that increasing thermal variability may have the greatest effects on community structure and function in tropical and temperate regions.
Highly similar microbial communities are shared among related and trophically similar ant species
Authors: ANDERSON KIRK E. , RUSSELL JACOB A. , MOREAU CORRIE S. , KAUTZ STEFANIE , SULLAM KAREN E. , HU YI , BASINGER URSULA , MOTT BRENDON M. , BUCK NORMAN , WHEELER DIANA E.
Published: January 2012

Ants dominate many terrestrial ecosystems, yet we know little about their nutritional physiology and ecology. While traditionally viewed as predators and scavengers, recent isotopic studies revealed that many dominant ant species are functional herbivores. As with other insects with nitrogen‐poor diets, it is hypothesized that these ants rely on symbiotic bacteria for nutritional supplementation. In this study, we used cloning and 16S sequencing to further characterize the bacterial flora of several herbivorous ants, while also examining the beta diversity of bacterial communities within and between ant species from different trophic levels. Through estimating phylogenetic overlap between these communities, we tested the hypothesis that ecologically or phylogenetically similar groups of ants harbor similar microbial flora. Our findings reveal: (i) clear differences in bacterial communities harbored by predatory and herbivorous ants; (ii) notable similarities among communities from distantly related herbivorous ants and (iii) similar communities shared by different predatory army ant species. Focusing on one herbivorous ant tribe, the Cephalotini, we detected five major bacterial taxa that likely represent the core microbiota. Metabolic functions of bacterial relatives suggest that these microbes may play roles in fixing, recycling, or upgrading nitrogen. Overall, our findings reveal that similar microbial communities are harbored by ants from similar trophic niches and, to a greater extent, by related ants from the same colonies, species, genera, and tribes. These trends hint at coevolved histories between ants and microbes, suggesting new possibilities for roles of bacteria in the evolution of both herbivores and carnivores from the ant family Formicidae.