bluuebunny/crossref_metadata_2025 huggingface dataset:
Invariance Property of the Stability Test with respect to the Characteristic Impedance
Authors: Ibrahim Amr A. , Darwish Ali M. , Hung H. Alfred
Published: May 2012

Stability of electrical amplifiers is of crucial importance. Among the popular stability tests is the μ-test which has many advantages over other tests like the K-Δ test. However, the value of μ parameter is dependent on the input/output terminal characteristic impedance used and this raises the concern that the predictions of the test are dependent on the choice of . This paper proves that the conclusions of the μ-test regarding stability/instability remain invariant with . This proof is necessary for gaining confidence in the results of the μ-test and should benefit circuit designers. Similar proofs should be extended to all other stability tests for additional insights into their validity under different circuit termination.
Hippocampal Dendritic Spines Modifications Induced by Perinatal Asphyxia
Authors: Saraceno G. E. , Castilla R. , Barreto G. E. , Gonzalez J. , Kölliker-Frers R. A. , Capani F.
Published: May 2012

Perinatal asphyxia (PA) affects the synaptic function and morphological organization. In previous works, we have shown neuronal and synaptic changes in rat neostriatum subjected to hypoxia leading to long-term ubi-protein accumulation. Since F-actin is highly concentrated in dendritic spines, modifications in its organization could be related with alterations induced by hypoxia in the central nervous system (CNS). In the present study, we investigate the effects of PA on the actin cytoskeleton of hippocampal postsynaptic densities (PSD) in 4-month-old rats. PSD showed an increment in their thickness and in the level of ubiquitination. Correlative fluorescence-electron microscopy photooxidation showed a decrease in the number of F-actin-stained spines in hippocampal excitatory synapses subjected to PA. Although Western Blot analysis also showed a slight decrease inβ-actin in PSD in PA animals, the difference was not significant. Taken together, this data suggests that long-term actin cytoskeleton might have role in PSD alterations which would be a spread phenomenon induced by PA.
Epidemiology, Etiology, Diagnosis, and Management of Placenta Accreta
Authors: Garmi Gali , Salim Raed
Published: May 2012

Placenta accreta is a severe pregnancy complication and is currently the most common indication for peripartum hysterectomy. It is becoming an increasingly common complication mainly due to the increasing rate of cesarean delivery. Main risk factor for placenta accreta is a previous cesarean delivery particularly when accompanied with a coexisting placenta previa. Antenatal diagnosis seems to be a key factor in optimizing maternal outcome. Diagnosis can be achieved by ultrasound in the majority of cases. Women with placenta accreta are usually delivered by a cesarean section. In order to avoid an emergency cesarean and to minimize complications of prematurity it is acceptable to schedule cesarean at 34 to 35 weeks. A multidisciplinary team approach and delivery at a center with adequate resources, including those for massive transfusion are both essential to reduce neonatal and maternal morbidity and mortality. The optimal management after delivery of the neonate is vague since randomized controlled trials and large cohort studies are lacking. Cesarean hysterectomy is probably the preferable treatment. In carefully selected cases, when fertility is desired, conservative management may be considered with caution. The current review discusses the epidemiology, predisposing factors, pathogenesis, diagnostic methods, clinical implications and management options of this condition.
A Note on Implicit and Explicit Mann Iterative Processes for Asymptotically ϕ‐Strongly Pseudocontractive Mappings
Authors: Muglia Luigi , Yao Yonghong
Published: May 2012

In this paper we prove the equivalence and the strong convergence of an explicit Mann iterative process and a modified implicit iterative process for asymptotically ϕ‐strongly pseudocontractive mappings in a uniformly smooth Banach space.
Nonprotein Structures from Mycobacteria: Emerging Actors for Tuberculosis Control
Authors: Lopez-Marin Luz M.
Published: May 2012

Immune response toMycobacterium tuberculosis, the causal agent of tuberculosis, is critical for protection. For many decades, consistent to classical biochemistry, most studies regarding immunity to the tubercle bacilli focused mainly on protein structures. But the atypical, highly impermeable and waxy coat of mycobacteria captured the interest of structural biologists very early, allowing the description of amazing molecules, such as previously unknown carbohydrates or fatty acids of astonishing lengths. From their discovery, cell wall components were identified as important structural pillars, but also as molecular motifs able to alter the human immune response. Recently, as new developments have emerged, classical conceptions of mycobacterial immune modulators have been giving place to unexpected discoveries that, at the turn of the last century, completely changed our perception of immunityvis-à-visfat compounds. In this paper, current knowledge about chemical and ultrastructural features of mycobacterial cell-wall is overviewed, with an emphasis on the relationships between cell-wall nonpeptide molecules and immune response. Remarks regarding the potential of these molecules for the development of new tools against tuberculosis are finally discussed.
Generalized Analytical Solutions for Nonlinear Positive-Negative Index Couplers
Authors: Kudyshev Zh. , Venugopal G. , Litchinitser N. M.
Published: May 2012

We find and analyze a generalized analytical solution for nonlinear wave propagation in waveguide couplers with opposite signs of the linear refractive index, nonzero phase mismatch between the channels, and arbitrary nonlinear coefficients.
New Classes of Spatial Central Configurations for N + N + 2‐Body Problem
Authors: Xuefei Liu , Chuntao Zhang , Jianmei Luo , Gan Zhang
Published: May 2012

Under arbitrary masses, in this paper, we discuss the existence of new families of spatial central configurations for the N + N + 2‐body problem, N ≥ 2. We study some necessary conditions and sufficient conditions for a families of spatial double pyramidical central configurations (d.p.c.c.), where 2N bodies are at the vertices of a nested regular N‐gons Γ1 ∪ Γ2, and the other two bodies are symmetrically located on the straight line that is perpendicular to the plane that contains Γ1 ∪ Γ2 and passes through the geometric center of Γ1 ∪ Γ2. We prove that if the bodies are in a d.p.c.c., then the masses on each N‐gon are equal, and the other two are also equal. And also we prove the existence and uniqueness of the central configurations for any given ratios of masses.
Some Applications of (C0, 1)‐Semigroups
Authors: Chang Yu-Hsien , Hong Cheng-hong
Published: May 2012

This study is originally motivated by the thermal balance equations for the gas and solid interphase heat‐transfer for the fast‐igniting catalytic converter of automobiles. Instead of solving this problem directly, we proved some results concerning the existence and uniqueness for abstract semilinear initial value problem by means of (C0, 1)‐semigroup theories on locally convex topological space. The most enjoyable here is that these results not only can be applied to solve the interphase heat‐transfer for the fast‐igniting catalytic converter of automobile under the situation of preheating at the entry edge of converter, but also can be applied to some other practical problems.
Histological, Immunohistological, and Clinical Features of Merkel Cell Carcinoma in Correlation to Merkel Cell Polyomavirus Status
Authors: Jaeger T. , Ring J. , Andres C.
Published: May 2012

Merkel cell carcinoma is a rare, but highly malignant tumor of the skin with high rates of metastasis and poor survival. Its incidence rate rises and is currently about 0.6/100000/year. Clinical differential diagnoses include basal cell carcinoma, cyst, amelanotic melanoma, lymphoma and atypical fibroxanthoma. In this review article clinical, histopathological and immunhistochemical features of Merkel cell carcinoma are reported. In addition, the role of Merkel cell polyomavirus is discussed.
Developmental Expression of the Pluripotency Factor Sal-Like Protein 4 in the Monkey, Human and Mouse Testis: Restriction to Premeiotic Germ Cells
Authors: Eildermann K. , Aeckerle N. , Debowski K. , Godmann M. , Christiansen H. , Heistermann M. , Schweyer S. , Bergmann M. , Kliesch S. , Gromoll J. , Ehmcke J. , Schlatt S. , Behr R.
Published: May 2012

SALL4 (sal-like protein 4) is a pluripotency transcription factor, which is highly expressed in embryonic stem (ES) cells and which is essential for mouse preimplantation development. In adult mouse organs, Sall4 mRNA is highly expressed in the testis and ovary, while there is only little or no expression in other organs. There is also a high expression of SALL4 in human testicular germ cell tumors. However, there is as yet no detailed analysis of SALL4 expression during mammalian testicular development. We analyzed SALL4 expression in ES cells, preimplantation embryos, and the developing and adult testis of a nonhuman primate (NHP) species, the common marmoset monkey (Callithrix jacchus). Immunofluorescence revealed SALL4 in the nuclei of marmoset ES cells and preimplantation embryos. Marmoset SALL4 isoform analysis in ES cells and newborn and adult testis by RT- PCR and Western blotting showed two different isoforms, SALL4-A and SALL4-B. Immunohistochemistry localized this transcription factor to the nuclei of primordial germ cells and most gonocytes in the prenatal and early postnatal marmoset testis. In the pubertal and adult testis SALL4 was present in undifferentiated spermatogonia. In the developing and adult human and mouse testis SALL4 expression mimicked the pattern in the marmoset. Adult testes from additional NHP species, the treeshrew, the cat and the dog also exhibited SALL4 in undifferentiated spermatogonia, indicating a conserved expression in the mammalian testis. Taking into account the importance of SALL4 for mouse development, we conclude that SALL4 may play an important role during mammalian germ cell development and is involved in the regulation of spermatogonial proliferation in the adult testis.
Evidence of the TNF-α System in the Human Achilles Tendon: Expression of TNF-α and TNF Receptor at both Protein and mRNA Levels in the Tenocytes
Authors: Gaida James Edmund , Bagge Johan , Purdam Craig , Cook Jill , Alfredson Håkan , Forsgren Sture
Published: May 2012

Understanding adaption to load is essential for prevention and treatment of tendinopathy/tendinosis. Cytokine release in response to load is one mechanism involved in mechanotransduction. The cytokine tumor necrosis factor alpha (TNF-α) is implicated in tendinosis and can induce apoptotic effects via tumor necrosis factor receptor 1 (TNFR1). The complete absence of information concerning the TNF-α system in Achilles tendon is a limitation as mid-portion Achilles tendinosis is very frequent. Purpose: To examine expression patterns of TNF-α and its two receptors (TNFR1 and TNFR2) in human Achilles tendinosis and control tissue and to biochemically confirm the presence of TNF-α in tendinosis tissue. Methods: TNF-α and TNFR1 mRNA were detected via in situ hybridization. TNF-α, TNFR1, and TNFR2 were demonstrated immunohistochemically. Apoptosis markers were utilized. ELISA was used to detect TNF-α. Results: TNF-α and TNFR1 mRNA was detected in tenocytes of both tendinosis and control tendons. Tenocytes from both groups displayed specific immunoreactions for TNF-α, TNFR1, and TNFR2. The widened/rounded tenocytes of tendinosis samples exhibited the most intense immunoreactions. Apoptosis was detected in only a subpopulation of the tenocytes in tendinosis tissue. TNF-α was measurable in tendinosis tissue. Inflammatory cells were not seen. Conclusion: This is the first evidence of the existence of the TNF-α system in the human Achilles tendon. Findings are confirmed at mRNA and protein levels as well as biochemically. The TNF-α system was in principle confined to the tenocytes. The connection between tenocyte morphology and the expression pattern of TNF-α, TNFR1, and TNFR2 suggests that the TNF-α system may be involved in tenocyte activation in Achilles tendinosis.
Modeling of Autism Genetic Variations in Mice: Focusing on Synaptic and Microcircuit Dysfunctions
Authors: Qiu Shenfeng , Aldinger Kimberly A. , Levitt Pat
Published: May 2012

Autism spectrum disorders (ASD) are heterogeneous neurodevelopmental disorders that are characterized by deficits in social interaction, verbal and nonverbal communication, and restrictive interests and repetitive behaviors. While human genetic studies have revealed marked heritability in ASD, it has been challenging to translate this genetic risk into a biological mechanism that influences brain development relevant to the disorder phenotypes. This is partly due to the complex genetic architecture of ASD, which involves de novo gene mutations, genomic abnormalities, and common genetic variants. Rather than trying to reconstitute the clinical disorder, using genetic model animals to examine specific features of core ASD pathophysiology offers unique opportunities for refining our understanding of neurodevelopmental mechanisms in ASD. A variety of ASD-relevant phenotypes can now be investigated in rodents, including stereotyped and repetitive behaviors, and deficits in social interaction and communication. In this review, we focus on several prevailing mouse models and discuss how studies have advanced our understanding of synaptic mechanisms that may underlie ASD pathophysiology. Although synaptic perturbations are not the only alterations relevant for ASD, we reason that understanding the synaptic underpinnings of ASD using mouse models may provide mechanistic insights into its etiology and lead to novel therapeutic and interventional strategies.
The Development and Neurobiology of Infant Attachment and Fear
Authors: Landers Margo S. , Sullivan Regina M.
Published: May 2012

Survival of altricial infants depends on attachment to the caregiver – a process that requires infants to identify, learn, remember, and approach their attachment figure. Here we review the neurobiology of attachment in infant rats where learning about the caregiver is supported by a specialized attachment neural circuitry to promote the infant-caregiver relationship. Specifically, the attachment circuit relies on infants acquiring learned preferences to the maternal odor, and this behavior is supported by the hyperfunctioning locus coeruleus and generous amounts of norepinephrine to produce experience-induced changes in the olfactory bulb and anterior piriform cortex. Infants also possess a reduced ability to acquire learned aversions or fear, and this behavior is facilitated through attenuated amygdala plasticity to block fear learning. Presumably, this attachment circuitry constrains the infant animal to express only learned preferences regardless of the quality of care received. As pups mature, and begin to travel in and out of the nest, the specialized attachment learning becomes contextually confined to when pups are with the mother. Thus, when outside the nest, these older pups show learning more typical of adult learning, presumably to prepare for independent life outside the nest. The quality of attachment can alter this circuitry, with early life stress prematurely terminating the pups’ access to the attachment system through premature functional activation of the amygdala. Overall, the attachment circuit appears to have a dual function: to keep pups close to the caregiver but also to shape pups’ behavior to match the environment and define long-term emotion and cognition.
The Role of Central Nervous System Development in Late-Onset Neurodegenerative Disorders
Authors: Palubinsky Amy M. , Martin Jacob A. , McLaughlin BethAnn
Published: May 2012

The human brain is dependent upon successfully maintaining ionic, energetic and redox homeostasis within exceptionally narrow margins for proper function. The ability of neurons to adapt to genetic and environmental perturbations and evoke a ‘new normal’ can be most fully appreciated in the context of neurological disorders in which clinical impairments do not manifest until late in life, although dysfunctional proteins are expressed early in development. We now know that proteins controlling ATP generation, mitochondrial stability, and the redox environment are associated with neurological disorders such as Parkinson’s disease and amyotrophic lateral sclerosis. Generally, focus is placed on the role that early or long-term environmental stress has in altering the survival of cells targeted by genetic dysfunctions; however, the central nervous system undergoes several periods of intense stress during normal maturation. One of the most profound periods of stress occurs when 50% of neurons are removed via programmed cell death. Unfortunately, we have virtually no understanding of how these events proceed in individuals who harbor mutations that are lethal later in life. Moreover, there is a profound lack of information on circuit formation, cell fate during development and neurochemical compensation in either humans or the animals used to model neurodegenerative diseases. In this review, we consider the current knowledge of how energetic and oxidative stress signaling differs between neurons in early versus late stages of life, the influence of a new group of proteins that can integrate cell stress signals at the mitochondrial level, and the growing body of evidence that suggests early development should be considered a critical period for the genesis of chronic neurodegenerative diseases.
Prenatal Cocaine Exposure Decreases Parvalbumin-Immunoreactive Neurons and GABA-to-Projection Neuron Ratio in the Medial Prefrontal Cortex
Authors: McCarthy Deirdre M. , Bhide Pradeep G.
Published: May 2012

Cocaine abuse during pregnancy produces harmful effects not only on the mother but also on the unborn child. The neurotransmitters dopamine and serotonin are known as the principal targets of the action of cocaine in the fetal and postnatal brain. However, recent evidence suggests that cocaine can impair cerebral cortical GABA neuron development and function. We sought to analyze the effects of prenatal cocaine exposure on the number and distribution of GABA and projection neurons (inhibitory interneurons and excitatory output neurons, respectively) in the mouse cerebral cortex. We found that the prenatal cocaine exposure decreased GABA neuron numbers and GABA-to-projection neuron ratio in the medial prefrontal cortex of 60-day-old mice. The neighboring prefrontal cortex did not show significant changes in either of these measures. However, there was a significant increase in projection neuron numbers in the prefrontal cortex but not in the medial prefrontal cortex. Thus, the effects of cocaine on GABA and projection neurons appear to be cortical region specific. The population of parvalbumin-immunoreactive GABA neurons was decreased in the medial prefrontal cortex following the prenatal cocaine exposure. The cocaine exposure also delayed the developmental decline in the volume of the medial prefrontal cortex. Thus, prenatal cocaine exposure produced persisting and region-specific effects on cortical cytoarchitecture and impaired the physiological balance between excitatory and inhibitory neurotransmission. These structural changes may underlie the electrophysiological and behavioral effects of prenatal cocaine exposure observed in animal models and human subjects.
Development and Characterization of NEX-Pten, a Novel Forebrain Excitatory Neuron-Specific Knockout Mouse
Authors: Kazdoba Tatiana M. , Sunnen C. Nicole , Crowell Beth , Lee Gum Hwa , Anderson Anne E. , D’Arcangelo Gabriella
Published: May 2012

The phosphatase and tensin homolog located on chromosome 10 (PTEN) suppresses the activity of the phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway, a signaling cascade critically involved in the regulation of cell proliferation and growth. Human patients carrying germ line PTEN mutations have an increased predisposition to tumors, and also display a variety of neurological symptoms and increased risk of epilepsy and autism, implicating PTEN in neuronal development and function. Consistently, loss of Pten in mouse neural cells results in ataxia, seizures, cognitive abnormalities, increased soma size and synaptic abnormalities. To better understand how Pten regulates the excitability of principal forebrain neurons, a factor that is likely to be altered in cognitive disorders, epilepsy and autism, we generated a novel conditional knockout mouse line (NEX-Pten) in which Cre, under the control of the NEX promoter, drives the deletion of Pten specifically in early postmitotic, excitatory neurons of the developing forebrain. Homozygous mutant mice exhibited a massive enlargement of the forebrain, and died shortly after birth due to excessive mTOR activation. Analysis of the neonatal cerebral cortex further identified molecular defects resulting from Pten deletion that likely affect several aspects of neuronal development and excitability.
A Multifaceted Role for apoE in the Clearance of Beta-Amyloid across the Blood-Brain Barrier
Authors: Bachmeier Corbin , Paris Daniel , Beaulieu-Abdelahad David , Mouzon Benoit , Mullan Michael , Crawford Fiona
Published: May 2012

Background: While apolipoprotein E4 (apoE4) is highly correlated with the development of Alzheimer’s disease (AD), its role in AD pathology and, in particular, beta-amyloid (Aβ) removal from the brain, is not clearly defined. Objective: To elucidate the influence of apoE on the clearance of Aβ across the blood-brain barrier (BBB). Methods: Aβ(1–42) was intracerebrally administered to transgenic mice expressing human apoE isoforms and examined in the periphery. Results: apoE3 and apoE4 mice had 5 times and 2 times, respectively, more Aβ(1–42) appearing in the plasma than wild-type or apoE knockout mice, indicating an enhanced clearance of Aβ from the brain to the periphery. In vitro, unbound basolateral apoE3 (i.e., not bound to Aβ), and to a lesser extent unbound apoE4, at concentrations ≤10 nm facilitated basolateral-to-apical fluorescein-Aβ(1–42) transcytosis across a BBB model, while apoE isoforms bound to Aβ significantly disrupted Aβ transcytosis. Additionally, following apical exposure to the BBB model, we found that apoE4 bound to Aβ is able to penetrate the BBB more readily than apoE3 bound to Aβ and does so via the RAGE (receptor for advanced glycation end products) transporter. Conclusion: These studies indicate a multifaceted, isoform-dependent role for apoE in the exchange of Aβ across the BBB and may partially explain the association of apoE4 and Aβ brain accumulation in AD.
Changes in Clinical Management and Diagnosis following DaTscan™ SPECT Imaging in Patients with Clinically Uncertain Parkinsonian Syndromes: A 12-Week Follow-Up Study
Authors: Kupsch Andreas , Bajaj Nin , Weiland Frederick , Tartaglione Antonio , Klutmann Susanne , Copp Ronald , Sherwin Paul , Tate Ann , Grachev Igor D.
Published: May 2012

Background: An accurate diagnosis is important for timely and adequate treatment in patients with clinically uncertain parkinsonian syndrome (CUPS). Objective: The objective of this study was to assess safety and changes in clinical management, diagnosis and quality of life (QoL) at 4 and 12 weeks following DaTscan™ (ioflupane [123I] injection) imaging in patients with CUPS. Methods: This randomized, open-label, single-dose, multicenter trial was carried out in patients with CUPS who were randomized to either a DaTscan imaging group or to a control group without imaging. The main outcome measures were the proportions of patients with changes in clinical management and diagnosis from baseline through to 12 weeks after DaTscan. A total of 19 university hospital centers in Europe and the USA participated in the study. There were 267 patients enrolled and randomized (131 DaTscan, 136 control). Results: Significantly more DaTscan patients had changes in clinical management after 12 weeks (p = 0.004) compared to the control group, and significantly more DaTscan patients had changes in diagnosis at 4 weeks and at 12 weeks (both p < 0.001) compared to control patients. No significant difference in total score for QoL was observed between groups during the study duration. DaTscan was safe and well-tolerated. No deaths, serious adverse events (AEs) or withdrawals due to AEs occurred during the study. One patient had a headache following treatment with a suspected relationship to DaTscan. Conclusion: DaTscan imaging significantly affected the clinical management and diagnosis of patients with CUPS. DaTscan is safe and well-tolerated and is a useful adjunct to differential diagnosis of CUPS.
Liver Regeneration after Liver Transplantation
Authors: Taki-Eldin A. , Zhou L. , Xie H.-Y. , Zheng S.-S.
Published: May 2012

Background/Purpose: The liver has a remarkable capacity to regenerate after injury or resection. The aim of this review is to outline the mechanisms and factors affecting liver regeneration after liver transplantation. Methods: Relevant studies were reviewed using Medline, PubMed and Springer databases. Results: A variety of cytokines (such as interleukin-6 and tumor necrosis factor-α), growth factors (like hepatocyte growth factor and transforming growth factor-α) and cells are involved in liver regeneration. Several factors affect liver regeneration after transplantation such as ischemic injury, graft size, immunosuppression, steatosis, donor age and viral hepatitis. Conclusion: Liver regeneration has been studied for many years. However, further research is essential to reveal the complex processes affecting liver regeneration, which may provide novel strategies in the management of liver transplantation recipients and donors.
Preweaning Sensorimotor Deficits and Adolescent Hypersociability in Grin1 Knockdown Mice
Authors: Moy Sheryl S. , Nikolova Viktoriya D. , Riddick Natallia V. , Baker Lorinda K. , Koller Beverly H.
Published: May 2012

Mice with knockdown of the N-methyl-d-aspartate (NMDA) receptor NR1 subunit, encoded by the gene Grin1, have been investigated as a model for the intrinsic NMDA hypofunction hypothesized for schizophrenia. Previous work has shown that adult Grin1 mutant mice have overt deficits in habituation and sensorimotor gating, exaggerated reactivity to environmental stimuli, reduced social approach, and other alterations that reflect behavioral manifestations of schizophrenia. In humans, the emergence of overt symptoms of the disorder typically occurs in adolescence or early adulthood, suggesting a role for aberrant maturation of NMDA receptor signaling in symptom onset. The following study evaluated Grin1 mutant mice for abnormal behavioral phenotypes during the preweaning, adolescent, and adult periods. Measures included open field activity, prepulse inhibition of acoustic startle responses, and social preference in a three-chamber choice task. Mice from the C57BL/6J inbred strain, one of the parental strains for the Grin1 line, were also tested. The results showed that developmental reduction of NMDA receptor function led to significant alterations in behavior during the second and third weeks of life, including exaggerated startle responses and sensorimotor gating deficits on postnatal day 13, and pronounced hypersociability in adolescence. Male Grin1 mutant mice were more susceptible than female mice to the detrimental effects of decreased NMDA signaling. Overall, these findings provide evidence that reduced Grin1 function leads to abnormal phenotypes in the preweaning period, and that deficient NMDA signaling can lead to both overt hypersociability or marked asociality, dependent upon sex and age.
Exercise Training Attenuates MuRF-1 Expression in the Skeletal Muscle of Patients With Chronic Heart Failure Independent of Age
Authors: Gielen Stephan , Sandri Marcus , Kozarez Irina , Kratzsch Jürgen , Teupser Daniel , Thiery Joachim , Erbs Sandra , Mangner Norman , Lenk Karsten , Hambrecht Rainer , Schuler Gerhard , Adams Volker
Published: May 2012

Background—

Muscle wasting occurs in both chronic heart failure (CHF) and normal aging and contributes to exercise intolerance and increased morbidity/mortality. However, the molecular mechanisms of muscle atrophy in CHF and their interaction with aging are still largely unknown. We therefore measured the activation of the ubiquitin-proteasome system and the lysosomal pathway of intracellular proteolysis in muscle biopsies of CHF patients and healthy controls in two age strata and assessed the age-dependent effects of a 4-week endurance training program on the catabolic-anabolic balance.

Methods and Results—

Sixty CHF patients (30 patients aged ≤55 years, mean age 46±5 years; 30 patients aged ≥65 years, mean age 72±5 years) and 60 healthy controls (30 subjects aged ≤55 years, mean age 50±5 years; 30 subjects aged ≥65 years, mean age 72±4 years) were randomized to 4 weeks of supervised endurance training or to a control group. Before and after the intervention, vastus lateralis muscle biopsies were obtained. The expressions of cathepsin-L and the muscle-specific E3 ligases MuRF-1 and MAFbx were measured by real-time polymerase chain reaction and confirmed by Western blot. At baseline, MuRF-1 expression was significantly higher in CHF patients versus healthy controls (mRNA: 624±59 versus 401±25 relative units;
P
=0.007). After 4 weeks of exercise training, MuRF-1 mRNA expression was reduced by −32.8% (
P
=0.02) in CHF patients aged ≤55 years and by −37.0% (
P
<0.05) in CHF patients aged ≥65 years.

Conclusions—

MuRF-1, a component of the ubiquitin-proteasome system involved in muscle proteolysis, is increased in the skeletal muscle of patients with heart failure. Exercise training results in reduced MuRF-1 levels, suggesting that it blocks ubiquitin-proteasome system activation and does so in both younger and older CHF patients.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00176319.
Pulmonary Hypertension in
Circulation
and the
Circulation
Subspecialty Journals
Authors:   The Editors
Published: May 2012

The following articles are being highlighted as part of
Circulation's
Topic Review series. This series will summarize the most important manuscripts, as selected by the editors, published in
Circulation
and the
Circulation
subspecialty journals. The studies included in this article represent the articles related to pulmonary hypertension that were published in
Circulation
and the
Circulation
subspecialty journals in 2010 and 2011.
Testosterone Induces Vascular Smooth Muscle Cell Migration by NADPH Oxidase and c-Src–Dependent Pathways
Authors: Chignalia Andreia Z. , Schuldt Elke Z. , Camargo Lívia L. , Montezano Augusto C. , Callera Gláucia E. , Laurindo Francisco R. , Lopes Lucia R. , Avellar Maria Christina W. , Carvalho Maria Helena C. , Fortes Zuleica B. , Touyz Rhian M. , Tostes Rita C.
Published: May 2012

Testosterone has been implicated in vascular remodeling associated with hypertension. Molecular mechanisms underlying this are elusive, but oxidative stress may be important. We hypothesized that testosterone stimulates generation of reactive oxygen species (ROS) and migration of vascular smooth muscle cells (VSMCs), with enhanced effects in cells from spontaneously hypertensive rats (SHRs). The mechanisms (genomic and nongenomic) whereby testosterone induces ROS generation and the role of c-Src, a regulator of redox-sensitive migration, were determined. VSMCs from male Wistar-Kyoto rats and SHRs were stimulated with testosterone (10
−7
mol/L, 0–120 minutes). Testosterone increased ROS generation, assessed by dihydroethidium fluorescence and lucigenin-enhanced chemiluminescence (30 minutes [SHR] and 60 minutes [both strains]). Flutamide (androgen receptor antagonist) and actinomycin D (gene transcription inhibitor) diminished ROS production (60 minutes). Testosterone increased
Nox1
and
Nox4
mRNA levels and p47phox protein expression, determined by real-time PCR and immunoblotting, respectively. Flutamide, actinomycin D, and cycloheximide (protein synthesis inhibitor) diminished testosterone effects on p47phox. c-Src phosphorylation was observed at 30 minutes (SHR) and 120 minutes (Wistar-Kyoto rat). Testosterone-induced ROS generation was repressed by 3-(4-chlorophenyl) 1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-day]pyrimidin-4-amine (c-Src inhibitor) in SHRs and reduced by apocynin (antioxidant/NADPH oxidase inhibitor) in both strains. Testosterone stimulated VSMCs migration, assessed by the wound healing technique, with greater effects in SHRs. Flutamide, apocynin, and 3-(4-chlorophenyl) 1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-day]pyrimidin-4-amine blocked testosterone-induced VSMCs migration in both strains. Our study demonstrates that testosterone induces VSMCs migration via NADPH oxidase–derived ROS and c-Src–dependent pathways by genomic and nongenomic mechanisms, which are differentially regulated in VSMCs from Wistar-Kyoto rats and SHRs.
Tumor Necrosis Factor α Decreases Nitric Oxide Synthase Type 3 Expression Primarily via Rho/Rho Kinase in the Thick Ascending Limb
Authors: Ramseyer Vanesa D. , Hong Nancy J. , Garvin Jeffrey L.
Published: May 2012

Inappropriate Na
+
reabsorption by thick ascending limbs (THALs) induces hypertension. NO produced by NO synthase type 3 (NOS3) inhibits NaCl reabsorption by THALs. Tumor necrosis factor α (TNF-α) decreases NOS3 expression in endothelial cells and contributes to increases in blood pressure. However, the effects of TNF-α on THAL NOS3 and the signaling cascade are unknown. TNF-α activates several signaling pathways, including Rho/Rho kinase (ROCK), which is known to reduce NOS3 expression in endothelial cells. Therefore, we hypothesized that TNF-α decreases NOS3 expression via Rho/ROCK in rat THAL primary cultures. THAL cells were incubated with either vehicle or 1 nmol/L of TNF-α for 24 hours, and NOS3 expression was measured by Western blot. TNF-α decreased NOS3 expression by 51±6% (
P
<0.002) and blunted stimulus-induced NO production. A 10-minute treatment with TNF-α stimulated RhoA activity by 60±23% (
P
<0.04). Inhibition of Rho GTPase with 0.05 μg/mL of C3 exoenzyme blocked TNF-α–induced reductions in NOS3 expression by 30±8% (
P
<0.02). Inhibition of ROCK with 10 μmol/L of H-1152 blocked TNF-α–induced decreases in NOS3 expression by 66±15% (
P
<0.001). Simultaneous inhibition of Rho and ROCK had no additive effect. Myosin light chain kinase, NO, protein kinase C, mitogen-activated kinase kinase, c-Jun amino terminal kinases, and Rac-1 were also not involved in TNF-α–induced decreases in NOS3 expression. We conclude that TNF-α decreases NOS3 expression primarily via Rho/ROCK in rat THALs. These data suggest that some of the beneficial effects of ROCK inhibitors in hypertension could be attributed to the mitigation of TNF-α–induced reduction in NOS3 expression.
Impact of introduced fish on Common frog (Rana temporaria) close to its altitudinal limit in alpine lakes
Authors: Tiberti Rocco , von Hardenberg Achaz
Published: May 2012

Alien fish species have been introduced into naturally fishless mountain lakes worldwide, with negative consequences for native fauna. This study describes the impact of introduced Brook trout (Salvelinus fontinalis) on Common frog (Rana temporaria) in the Gran Paradiso National Park (Western Italian Alps). We conducted an extensive, six years long (2006-2011) monitoring campaign over 12 fishless and 8 stocked lakes, close to the new altitudinal limit ofR. temporaria(2811 m a.s.l.). This new altitudinal limit is reported for the first time in this study. The presence of introduced fish was a factor of ecological exclusion, negatively affecting the presence of frogs and compromising the suitability of alpine lakes as breeding sites. These results are likely to depend on larval predation or to selective avoidance of stocked lakes byR. temporaria. Eradication of introduced fish is proposed as a conservation measure to recover amphibian populations in alpine lake ecosystems.
Are there real sexual morphometric differences in yellow-bellied toads (Bombina spp.; Bombinatoridae)?
Authors: Di Cerbo Anna Rita , Biancardi Carlo M.
Published: May 2012

In this study, we explored the level and pattern of sexual size dimorphism and sexual shape dimorphism in two closely related Bombina species that have low levels of sexual dimorphism in body size and shape. We applied an experimental protocol to explore sexual variations in morphological traits, including a preliminary evaluation of the measurement error. Mean measurement error (MME) and measurement error index (MEI) were estimated on each of the eleven morphometric variables to exclude any possible subjective factor in measuring and to perform, for the first time, an objective functional and statistical evaluation of sexual size differences in the two species. Even if statistically significant, each difference that lies below the level of uncertainty of the measure could not be reliable. Therefore, statistically significant differences in head shape have been rejected, due to an average difference between males and females smaller than the possible MME. We detected significantly longer distal segments of the hind limbs in males, which could account for their use in mating behaviour (e.g. scramble competition, water-wave communication). However, major and more reliable evidences of sexual dimorphism have been found on forelimb measures (MEI > 1), in particular humerus length and amplexus, which are significantly larger in males than in females. These results indicate a mating related sexual dimorphism, when larger and stronger forelimbs can give an advantage during coupling as well as during male-male fighting. The mean measurement error values and formulas provided in this work could be applied to future morphometric studies on Bombina species.
The pine wood nematode, Bursaphelenchus xylophilus, in Portugal: possible introductions and spread routes of a serious biological invasion revealed by molecular methods
Authors: Valadas Vera , Laranjo Marta , Barbosa Pedro , Espada Margarida , Mota Manuel , Oliveira Solange
Published: May 2012

The pine wood nematode (PWN), Bursaphelenchus xylophilus, the causal agent of pine wilt disease (PWD), is a major world-wide pathogen and pest of pine, with impacts on forest health, natural ecosystem stability and international trade. In Portugal, PWN was first diagnosed in 1999, the first occurrence also for Europe. The disease was recently detected on the island of Madeira and in northern Spain. In an attempt to search for more reliable and robust molecular markers that enable the study of intraspecific variability of B. xylophilus from different geographic locations, the intergenic spacer (IGS) region of the 5S rRNA gene and inter-simple sequence repeats (ISSR) analysis were used to determine the genetic relationships among 43 B. xylophilus isolates from Portugal, China, Japan, South Korea and USA. IGS sequence analysis showed that this region can only be used to establish interspecific relationships, since no differences were detected among Portuguese isolates from different geographic locations. Fingerprints obtained with ISSR show high genetic variability among Portuguese isolates, except for the ones obtained prior to 2008. The ISSR dendrogram suggests the spread of the disease inside continental Portugal and to Madeira. Until 2008, B. xylophilus populations found in continental Portugal showed low genetic diversity, pointing to a single introduction, probably from Asia, whereas recent populations from continental Portugal (2009-2010) and Madeira show high genetic diversity, suggesting multiple introductions from different origins.
Is Justification Dialectical?
Authors: Willem Wieland Jan
Published: May 2012

Much of present-day epistemology is divided between internalists and externalists. Different as these views are, they have in common that they strip justification from its dialectical component in order to block the skeptic’s argument from disagreement. That is, they allow that one may have justified beliefs even if one is not able to defend it against challenges and resolve the disagreements about them. Markus Lammenranta recently argued that neither internalism nor externalism convinces if we consider the argument in its most interesting format. In this paper I zoom in on this debate, and fix further details of Lammenranta’s lead. Specifically, I will side with skepticism that justification is dialectical, yet only if certain conditions are in place.
Investigating Interannual Variability of Precipitation at the Global Scale: Is There a Connection with Seasonality?
Authors: Fatichi S. , Ivanov V. Yu. , Caporali E.
Published: May 2012

Interannual variability of precipitation can directly or indirectly affect many hydrological, ecological, and biogeochemical processes that, in turn, influence climate. Despite the significant importance of the phenomenon, few studies have attempted to elucidate spatial patterns of this variability at the global scale. This study uses land gauge precipitation records of the Global Historical Climatology Network, version 2, as well as reanalysis data to provide an assessment of the spatial organization of characteristics of precipitation interannual variability. The coefficient of variation, skewness, and short- and long-range dependence of the precipitation variability are analyzed. Among the major inferences is that the coefficient of variation of annual precipitation shows a significant correlation with intra-annual seasonality. Specifically, subyearly precipitation anomalies occurring in locations with pronounced seasonality affect the total yearly amount, imposing a higher variability in the annual precipitation fluctuations. Furthermore, the study illustrates that a positive skewness of the distribution of annual precipitation is a robust property worldwide and its magnitude is related to the coefficient of variation. Additionally, annual precipitation exhibits very weak small-lag autocorrelation. Conversely, the intensity of long-memory–long-range dependence is significantly larger than zero, hinting that organized long-term variations are an important feature of the interannual variability of precipitation.
Assessing the Influence of the MJO on Strong Precipitation Events in Subtropical, Semi-Arid North-Central Chile (30°S)
Authors: Juliá Cristóbal , Rahn David A. , Rutllant José A.
Published: May 2012

Annual precipitation in subtropical, semiarid north-central Chile (30°S) during rainy years comprises a few (3–5) strong events in the fall and winter, which are presumably modulated by the Madden–Julian oscillation (MJO). Precipitation from 1979–2009 was recorded daily at three stations along the Elqui Valley. The relationship between the MJO and precipitation is investigated from two perspectives: 1) examining a MJO index (MJOI) based on the actual precipitation events and 2) examining the likelihood of precipitation based on a favorable MJOI. About 80% of the strong precipitation events at the coast in La Serena are related to an active MJO near the central equatorial Pacific. These events are often typified by broad, slow moving synoptic systems in phase with the MJO propagation. Blocking in the far southeast Pacific is associated with precipitation 75% of the time, while deep troughs make up the rest.

A relationship between a MJOI and strong rainfall suggests that, though it could be used as a potential diagnostic, the number of cases where there is a favorable MJOI but no precipitation (i.e., false alarms) limits its utility. Additional criteria such as the Southern Oscillation (SO) and Antarctic Oscillation (AAO) phases were used to reject false alarms. Rejecting cases with positive values of the SO index reduced the number of false alarms from 70% to 58%, leaving about two false alarms for every correctly diagnosed event. The AAO index could not discriminate between false alarms and real cases. While a favorable MJOI increases the likelihood of precipitation in the Elqui Valley, false alarms remain problematic.
Forecast Advisory for the Late Fall Heavy Rainfall/Flood Event in Central Vietnam Developed from Diagnostic Analysis
Authors: Chen Tsing-Chang , Yen Ming-Cheng , Tsay Jenq-Dar , Alpert Jordan , Tan Thanh Nguyen Thi
Published: May 2012

The formations of heavy rainfall/flood (HRF) events in Vietnam are studied from diagnostic analyses of 31 events during the period 1979–2009. HRF events develop from the cold surge vortices formed around the Philippines. These vortices’ speed, size, and rainfall, which evolve into HRF events, are enhanced distinguishably from non-HRF vortices, as they reach Vietnam. The HRF cyclone, the North Pacific anticyclone, and the northwestern Pacific explosive cyclone simultaneously reach their maximum intensities when the HRF event occurs. An HRF cyclone attains its maximum intensity by the in-phase constructive interference of three monsoon (30–60, 12–24, and 5 days) modes identified by the spectral analysis of zonal winds. The rainfall center of an HRF event is formed and maintained by the in-phase constructive interference of rainfall and convergence of water vapor flux anomalies, respectively, from three monsoon modes. Forecast times of regional models are dependent and constrained on the scale of the limited domain. For 5-day forecasts, a global or at least a hemispheric model is necessary. Using the salient features described above, a 5-day forecast advisory is introduced to supplement forecasts of HRF events made by the global model. Non-HRF vortices are filtered by threshold values for the deepening rate of explosive cyclones and basic characteristics of the HRF events predicted by the global model. A necessary condition for an HRF event is the in-phase superposition of the three monsoon modes. One-week forecasts for 12 HRF events issued by the NCEP Global Forecast System are tested. Results demonstrate the feasibility of the forecast advisory to predict the occurrence dates of HRF events.
Formal and informal social capital and self-rated health in Europe: A new test of accumulation and compensation mechanisms using a multi-level perspective
Authors: Huijts Tim , Kraaykamp Gerbert
Published: May 2012

In this study, we simultaneously examined the influence of both informal and formal social capital at the individual and at the national level on health. Information from the first wave of European Social Surveys (2002) on 29,050 individuals from 17 European countries and Israel was analysed using multi-level regression models. We controlled for several individual and national characteristics. Self-rated health was used as an indicator of people’s general health status. First, we found that individual formal and informal social capital is positively related to health in almost all countries, but that the strength of these associations varies markedly across societies. Second, we found that the health of those who lack informal social networks as individuals is better in countries with high levels of informal and formal social capital. On the other hand, individuals lacking formal social networks are not compensated by high levels of formal and informal social capital at the national level. We conclude that including informal social capital is important to obtain a comprehensive view on the role of contextual social capital as a compensatory source for individuals lacking social networks.