bluuebunny/crossref_metadata_2025 huggingface dataset:
Respondent-driven sampling on the Thailand-Cambodia border. I. Can malaria cases be contained in mobile migrant workers?
Authors: Khamsiriwatchara Amnat , Wangroongsarb Piyaporn , Thwing Julie , Eliades James , Satimai Wichai , Delacollette Charles , Kaewkungwal Jaranit
Published: May 2011

Background

Reliable information on mobility patterns of migrants is a crucial part of the strategy to contain the spread of artemisinin-resistant malaria parasites in South-East Asia, and may also be helpful to efforts to address other public health problems for migrants and members of host communities. In order to limit the spread of malarial drug resistance, the malaria prevention and control programme will need to devise strategies to reach cross-border and mobile migrant populations.

Methodology

The Respondent-driven sampling (RDS) method was used to survey migrant workers from Cambodia and Myanmar, both registered and undocumented, in three Thai provinces on the Thailand-Cambodia border in close proximity to areas with documented artemisinin-resistant malaria parasites. 1,719 participants (828 Cambodian and 891 Myanmar migrants) were recruited. Subpopulations of migrant workers were analysed using the Thailand Ministry of Health classification based on length of residence in Thailand of greater than six months (long-term, or M1) or less than six months (short-term, or M2). Key information collected on the structured questionnaire included patterns of mobility and migration, demographic characteristics, treatment-seeking behaviours, and knowledge, perceptions, and practices about malaria.

Results

Workers from Cambodia came from provinces across Cambodia, and 22% of Cambodian M1 and 72% of Cambodian M2 migrants had been in Cambodia in the last three months. Less than 6% returned with a frequency of greater than once per month. Of migrants from Cambodia, 32% of M1 and 68% of M2 were planning to return, and named provinces across Cambodia as their likely next destinations. Most workers from Myanmar came from Mon state (86%), had never returned to Myanmar (85%), and only 4% stated plans to return.

Conclusion

Information on migratory patterns of migrants from Myanmar and Cambodia along the malaria endemic Thailand-Cambodian border within the artemisinin resistance containment zone will help target health interventions, including treatment follow-up and surveillance.
Identification of the protease cleavage sites in a reconstituted Gag polyprotein of an HERV-K(HML-2) element
Authors: George Maja , Schwecke Torsten , Beimforde Nadine , Hohn Oliver , Chudak Claudia , Zimmermann Anja , Kurth Reinhard , Naumann Dieter , Bannert Norbert
Published: May 2011

Background

The human genome harbors several largely preserved HERV-K(HML-2) elements. Although this retroviral family comes closest of all known HERVs to producing replication competent virions, mutations acquired during their chromosomal residence have rendered them incapable of expressing infectious particles. This also holds true for the HERV-K113 element that has conserved open reading frames (ORFs) for all its proteins in addition to a functional LTR promoter. Uncertainty concerning the localization and impact of post-insertional mutations has greatly hampered the functional characterization of these ancient retroviruses and their proteins. However, analogous to other betaretroviruses, it is known that HERV-K(HML-2) virions undergo a maturation process during or shortly after release from the host cell. During this process, the subdomains of the Gag polyproteins are released by proteolytic cleavage, although the nature of the mature HERV-K(HML-2) Gag proteins and the exact position of the cleavage sites have until now remained unknown.

Results

By aligning the amino acid sequences encoded by the gag-pro-pol ORFs of HERV-K113 with the corresponding segments from 10 other well-preserved human specific elements we identified non-synonymous post-insertional mutations that have occurred in this region of the provirus. Reversion of these mutations and a partial codon optimization facilitated the large-scale production of maturation-competent HERV-K113 virus-like particles (VLPs). The Gag subdomains of purified mature VLPs were separated by reversed-phase high-pressure liquid chromatography and initially characterized using specific antibodies. Cleavage sites were identified by mass spectrometry and N-terminal sequencing and confirmed by mutagenesis. Our results indicate that the gag gene product Pr74Gag of HERV-K(HML-2) is processed to yield p15-MA (matrix), SP1 (spacer peptide of 14 amino acids), p15, p27-CA (capsid), p10-NC (nucleocapsid) and two C-terminally encoded glutamine- and proline-rich peptides, QP1 and QP2, spanning 23 and 19 amino acids, respectively.

Conclusions

Expression of reconstituted sequences of original HERV elements is an important tool for studying fundamental aspects of the biology of these ancient viruses. The analysis of HERV-K(HML-2) Gag processing and the nature of the mature Gag proteins presented here will facilitate further studies of the discrete functions of these proteins and of their potential impact on the human host.
Changes in white adipose tissue metabolism induced by resveratrol in rats
Authors: Alberdi Goiuri , Rodríguez Víctor M , Miranda Jonatan , Macarulla María T , Arias Noemí , Andrés-Lacueva Cristina , Portillo María P
Published: May 2011

Background

A remarkable range of biological functions have been ascribed to resveratrol. Recently, this polyphenol has been shown to have body fat lowering effects. The aim of the present study was to assess some of the potential underlying mechanisms of action which take place in adipose tissue.

Methods

Sixteen male Sprague-Dawley rats were randomly divided into two groups: control and treated with 30 mg resveratrol/kg body weight/d. All rats were fed an obesogenic diet and after six weeks of treatment white adipose tissues were dissected. Lipoprotein lipase activity was assessed by fluorimetry, acetyl-CoA carboxylase by radiometry, and malic enzyme, glucose-6P-dehydrogenase and fatty acid synthase by spectrophotometry. Gene expression levels of acetyl-CoA carboxylase, fatty acid synthase, lipoprotein lipase, hormone-sensitive lipase, adipose triglyceride lipase, PPAR-gamma, SREBP-1c and perilipin were assessed by Real time RT-PCR. The amount of resveratrol metabolites in adipose tissue was measured by chromatography.

Results

There was no difference in the final body weight of the rats; however, adipose tissues were significantly decreased in the resveratrol-treated group. Resveratrol reduced the activity of lipogenic enzymes, as well as that of heparin-releasable lipoprotein lipase. Moreover, a significant reduction was induced by this polyphenol in hormone-sensitive lipase mRNA levels. No significant changes were observed in other genes. Total amount of resveratrol metabolites in adipose tissue was 2.66 ± 0.55 nmol/g tissue.

Conclusions

It can be proposed that the body fat-lowering effect of resveratrol is mediated, at least in part, by a reduction in fatty acid uptake from circulating triacylglycerols and also in de novo lipogenesis.
Rationale, design and methodology for Intraventricular Pressure Gradients Study: a novel approach for ventricular filling assessment in normal and falling hearts
Authors: Guerra Miguel , Amorim Mário J , Mota João C , Vouga Luís , Leite-Moreira# Adelino
Published: May 2011

Background

Intraventricular pressure gradients have been described between the base and the apex of the left ventricle during early diastolic ventricular filling, as well as, their increase after systolic and diastolic function improvement. Although, systolic gradients have also been observed, data are lacking on their magnitude and modulation during cardiac dysfunction. Furthermore, we know that segmental dysfunction interferes with the normal sequence of regional contraction and might be expected to alter the physiological intraventricular pressure gradients. The study hypothesis is that systolic and diastolic gradients, a marker of normal left ventricular function, may be related to physiological asynchrony between basal and apical myocardial segments and they can be attenuated, lost entirely, or even reversed when ventricular filling/emptying is impaired by regional acute ischemia or severe aortic stenosis.

Methods/Design

Animal Studies: Six rabbits will be completely instrumented to measuring apex to outflow-tract pressure gradient and apical and basal myocardial segments lengthening changes at basal, afterloaded and ischemic conditions. Afterload increase will be performed by abruptly narrowing or occluding the ascending aorta during the diastole and myocardial ischemia will be induced by left coronary artery ligation, after the first diagonal branch.

Patient Studies: Patients between 65-80 years old (n = 12), both genders, with severe aortic stenosis referred for aortic valve replacement will be selected as eligible subjects. A high-fidelity pressure-volume catheter will be positioned through the ascending aorta across the aortic valve to measure apical and outflow-tract pressure before and after aortic valve replacement with a bioprosthesis. Peak and average intraventricular pressure gradients will be recorded as apical minus outflow-tract pressure and calculated during all diastolic and systolic phases of cardiac cycle.

Discussion

We expect to validate the application of our method to obtain intraventricular pressure gradients in animals and patients and to promote a methodology to better understand the ventricular relaxation and filling and their correlation with systolic function.
Car sunshade-induced craniofacial injury: a case report
Authors: Sharif-Alhoseini Mahdi , Khatibi Hadi , Chardoli Mojtaba , Rahimi-Movaghar Vafa
Published: May 2011

Introduction

We report the case of a man who sustained a craniofacial injury after spontaneous lateral airbag deployment resulting in his face being struck by a car sunshade. This highlights the potential damage that can be caused by any object placed between a lateral airbag and a car occupant.

Case presentation

We report the case of a 33-year-old Caucasian man who was the driver in a frontal collision. He had opened the car sunshade and turned it 90° towards the left. As he was driving, he struck a bus, causing the driver's lateral airbag to spontaneously deploy. The airbag pushed the sunshade against his face and injured him.

Conclusions

Car sunshades can cause significant craniofacial injury. We suggest that sunshade design must be improved to reduce the risk of potential injuries to car occupants. We recommend a new, safer sunshade design.
A Metabolic Biofuel Cell: Conversion of Human Leukocyte Metabolic Activity to Electrical Currents
Authors: Justin Gusphyl A , Zhang Yingze , Cui X Tracy , Bradberry Charles W , Sun Mingui , Sclabassi Robert J
Published: May 2011

An investigation of the electrochemical activity of human white blood cells (WBC) for biofuel cell (BFC) applications is described. WBCs isolated from whole human blood were suspended in PBS and introduced into the anode compartment of a proton exchange membrane (PEM) fuel cell. The cathode compartment contained a 50 mM potassium ferricyanide solution. Average current densities between 0.9 and 1.6 μA cm-2 and open circuit potentials (Voc) between 83 and 102 mV were obtained, which were both higher than control values. Cyclic voltammetry was used to investigate the electrochemical activity of the activated WBCs in an attempt to elucidate the mechanism of electron transfer between the cells and electrode. Voltammograms were obtained for the WBCs, including peripheral blood mononuclear cells (PBMCs - a lymphocyte-monocyte mixture isolated on a Ficoll gradient), a B lymphoblastoid cell line (BLCL), and two leukemia cell lines, namely K562 and Jurkat. An oxidation peak at about 363 mV vs. SCE for the PMA (phorbol ester) activated primary cells, with a notable absence of a reduction peak was observed. Oxidation peaks were not observed for the BLCL, K562 or Jurkat cell lines. HPLC confirmed the release of serotonin (5-HT) from the PMA activated primary cells. It is believed that serotonin, among other biochemical species released by the activated cells, contributes to the observed BFC currents.
Prevalence of sacral dysmorphia in a prospective trauma population: Implications for a "safe" surgical corridor for sacro-iliac screw placement
Authors: Hasenboehler Erik A , Stahel Philip F , Williams Allison , Smith Wade R , Newman Justin T , Symonds David L , Morgan Steven J
Published: May 2011

Background

Percutaneous sacro-iliac (SI) screw fixation represents a widely used technique in the management of unstable posterior pelvic ring injuries and sacral fractures. The misplacement of SI-screws under fluoroscopic guidance represents a critical complication for these patients. This study was designed to determine the prevalence of sacral dysmorphia and the radiographic anatomy of surgical S1 and S2 corridors in a representative trauma population.

Methods

Prospective observational cohort study on a consecutive series of 344 skeletally mature trauma patients of both genders enrolled between January 1, 2007, to September 30, 2007, at a single academic level 1 trauma center. Inclusion criteria included a pelvic CT scan as part of the initial diagnostic trauma work-up. The prevalence of sacral dysmorphia was determined by plain radiographic pelvic films and CT scan analysis. The anatomy of sacral corridors was analyzed on 3 mm reconstruction sections derived from multislice CT scan, in the axial, coronal, and sagittal plane. "Safe" potential surgical corridors at S1 and S2 were calculated based on these measurements.

Results

Radiographic evidence of sacral dysmorphia was detected in 49 patients (14.5%). The prevalence of sacral dysmorphia was not significantly different between male and female patients (12.2%vs. 19.2%;P= 0.069). In contrast, significant gender-related differences were detected with regard to radiographic analysis of surgical corridors for SI-screw placement, with female trauma patients (n= 99) having significantly narrower corridors at S1 and S2 in all evaluated planes (axial, coronal, sagittal), compared to male counterparts (n= 245;P< 0.01). In addition, the mean S2 body height was higher in dysmorphic compared to normal sacra, albeit without statistical significance (P= 0.06), implying S2 as a safe surgical corridor of choice in patients with sacral dysmorphia.

Conclusions

These findings emphasize a high prevalence of sacral dysmorphia in a representative trauma population and imply a higher risk of SI-screw misplacement in female patients. Preoperative planning for percutaneous SI-screw fixation for unstable pelvic and sacral fractures must include a detailed CT scan analysis to determine the safety of surgical corridors.
The distribution of potential West Nile virus vectors, Culex pipiens pipiens and Culex pipiens quinquefasciatus (Diptera: Culicidae), in Mexico City
Authors: Diaz-Badillo Alvaro , Bolling Bethany G , Perez-Ramirez Gerardo , Moore Chester G , Martinez-Munoz Jorge P , Padilla-Viveros America A , Camacho-Nuez Minerva , Diaz-Perez Alfonso , Beaty Barry J , de Lourdes Munoz Maria
Published: May 2011

Background

Culex spp. mosquitoes are considered to be the most important vectors of West Nile virus (WNV) detected in at least 34 species of mosquitoes in the United States. In North America, Culex pipiens pipiens, Culex pipiens quinquefasciatus, and Culex tarsalis are all competent vectors of WNV, which is considered to be enzootic in the United States and has also been detected in equines and birds in many states of Mexico and in humans in Nuevo Leon. There is potential for WNV to be introduced into Mexico City by various means including infected mosquitoes on airplanes, migrating birds, ground transportation and infected humans. Little is known of the geographic distribution of Culex pipiens complex mosquitoes and hybrids in Mexico City. Culex pipiens pipiens preferentially feed on avian hosts; Culex pipiens quinquefasciatus have historically been considered to prefer mammalian hosts; and hybrids of these two species could theoretically serve as bridge vectors to transmit WNV from avian hosts to humans and other mammalian hosts. In order to address the potential of WNV being introduced into Mexico City, we have determined the identity and spatial distribution of Culex pipiens complex mosquitoes and their hybrids.

Results

Mosquito larvae collected from 103 sites throughout Mexico City during 2004-2005 were identified as Culex, Culiseta or Ochlerotatus by morphological analysis. Within the genus Culex, specimens were further identified as Culex tarsalis or as belonging to the Culex pipiens complex. Members of the Culex pipiens complex were separated by measuring the ratio of the dorsal and ventral arms (DV/D ratio) of the male genitalia and also by using diagnostic primers designed for the Ace.2 gene. Culex pipiens quinquefasciatus was the most abundant form collected.

Conclusions

Important WNV vectors species, Cx. p. pipiens, Cx. p. quinquefasciatus and Cx. tarsalis, are all present in Mexico City. Hybrids of Cx. p. pipiens and Cx. p. quinquefasciatus were also collected and identified. The presence and abundance of these WNV competent vectors is a cause for concern. Understanding the distribution of these vectors can help improve viral surveillance activities and mosquito control efforts in Mexico City.
The Antagonists But Not Partial Agonists of Glucocorticoid Receptor Ligands Show Substantial Side Effect Dissociation
Authors: Hu Xiao , Du Sarah , Tunca Cansu , Braden Timothy , Long Kelly R. , Lee Jamie , Webb Elizabeth G. , Dietz Jessica D. , Hummert Susan , Rouw Sharon , Hegde Shridhar G. , Webber R. Keith , Obukowicz Mark G.
Published: May 2011

A synthetic glucocorticoid receptor (GR) ligand with the efficacy of a glucocorticoid, but without the accompanying side effects, would meet an unmet medical need for the treatment of inflammatory diseases. It was hypothesized that a GR ligand that shifted helix 12 in a manner distinct from an agonist and an antagonist would confer a distinct GR conformation, resulting in differential gene expression and, ultimately, dissociation of antiinflammatory activity from side effects. A structural feature expected to interfere with helix 12 was incorporated into a nonsteroidal, tricyclic scaffold to create novel, high-affinity, and selective GR ligands that manifested a dual function in cellular assays, partial but robust agonist activity for inflammatory cytokine inhibition, and full antagonist activity for reporter gene activation. In contrast, analogs not likely to hinder helix 12 exhibited partial agonist activity for reporter gene activation. The requirement of full antagonist activity for substantial side effect dissociation was demonstrated in primary human preadipocytes, hepatocytes, and osteoblasts in which effects on adipogenesis, key genes involved in gluconeogenesis, and genes important for bone formation were examined, respectively. The dissociated GR ligands, despite lacking significant reporter gene activation, weakly recruit a limited number of coactivators such as peroxisomal proliferator-activated receptor-γ coactivator 1α. Transcriptional activation was sensitive to both peroxisomal proliferator-activated receptor-γ coactivator 1α and GR levels, providing a basis for cell-selective modulation of gene expression. The antiinflammatory activity of the dissociated ligands was further demonstrated in mouse models of inflammation. Together these results suggest that these ligands are promising candidates with robust antiinflammatory activity and likely dissociation against glucocorticoid-induced side effects.
Gastrin Treatment Stimulates β-Cell Regeneration and Improves Glucose Tolerance in 95% Pancreatectomized Rats
Authors: Téllez Noèlia , Joanny Géraldine , Escoriza Jéssica , Vilaseca Marina , Montanya Eduard
Published: May 2011

β-Cell mass reduction is a central aspect in the development of type 1 and type 2 diabetes, and substitution or regeneration of the lost β-cells is a potentially curative treatment of diabetes. To study the effects of gastrin on β-cell mass in rats with 95% pancreatectomy (95%-Px), a model of pancreatic regeneration, rats underwent 95% Px or sham Px and were treated with [15 leu] gastrin-17 (Px+G and S+G) or vehicle (Px+V and S+V) for 15 d. In 95% Px rats, gastrin treatment reduced hyperglycemia (280 ± 52 mg vs. 436 ± 51 mg/dl, P < 0.05), and increased β-cell mass (1.15 ± 0.15 mg)) compared with vehicle-treated rats (0.67 ± 0.15 mg, P < 0.05). Gastrin treatment induced β-cell regeneration by enhancing β-cell neogenesis (increased number of extraislet β-cells in Px+G: 0.42 ± 0.05 cells/mm2vs. Px+V: 0.27 ± 0.07 cells/mm2, P < 0.05, and pancreatic and duodenal homeobox 1 expression in ductal cells of Px+G: 1.21 ± 0.38% vs. Px+V: 0.23 ± 0.10%, P < 0.05) and replication (Px+G: 1.65 ± 0.26% vs. S+V: 0.64 ± 0.14%; P < 0.05). In addition, reduced β-cell apoptosis contributed to the increased β-cell mass in gastrin-treated rats (Px+G: 0.07 ± 0.02%, Px+V: 0.23 ± 0.05%; P < 0.05). Gastrin action on β-cell regeneration and survival increased β-cell mass and improved glucose tolerance in 95% Px rats, supporting a potential role of gastrin in the treatment of diabetes.
Single-molecule binding of CD44 to fibrin versus P-selectin predicts their distinct shear-dependent interactions in cancer
Authors: Raman Phrabha S. , Alves Christina S. , Wirtz Denis , Konstantopoulos Konstantinos
Published: May 2011

P-selectin and fibrin(ogen) have pivotal roles in the hematogenous dissemination of tumor cells. CD44 variant isoforms, CD44v, have been identified as the major functional P-selectin ligands and fibrin receptors on metastatic colon carcinoma cells. The molecular recognition of CD44v by fibrin mediates firm adhesion at low shear, whereas CD44v–P-selectin binding supports transient rolling interactions at elevated shear stresses and low site densities of P-selectin. We used single-molecule force spectroscopy to provide a molecular interpretation for these two distinct adhesion events. The CD44v–P-selectin bond has a longer unstressed equilibrium lifetime, a lower reactive compliance and a higher tensile strength relative to the CD44v–fibrin bond. These intrinsic differences confer the ability to the CD44v–P-selectin pair to mediate binding at higher shear stresses. Increasing the duration of receptor–ligand contact (2–200 milliseconds) did not affect the micromechanical properties of the CD44v–P-selectin bond, but it increased the tensile strength and the depth of the free energy barrier of the CD44v–fibrin bond and decreased its reactive compliance. This bond strengthening at longer interaction times might explain why CD44v binding to immobilized fibrin occurs at low shear. Single-molecule characterization of receptor–ligand binding can predict the shear-dependent adhesive interactions between cells and substrates observed both in vitro and in vivo.
Romo1 is a negative-feedback regulator of Myc
Authors: Lee Seung Baek , Kim Jung Jin , Chung Jin Sil , Lee Myeong-Sok , Lee Kee-Ho , Kim Byung Soo , Do Yoo Young
Published: May 2011

Degradation of Myc protein is mediated by E3 ubiquitin ligases, including SCFFbw7 and SCFSkp2, but much remains unknown about the mechanism of S-phase kinase-associated protein (Skp2)-mediated Myc degradation. In the present study, we show that upregulated Myc protein, which triggers the G1–S phase progression in response to growth-stimulatory signals, induces reactive oxygen species modulator 1 (Romo1) expression. Romo1 subsequently triggers Skp2-mediated ubiquitylation and degradation of Myc by a mechanism not previously reported in normal lung fibroblasts. We also show that reactive oxygen species (ROS) derived from steady-state Romo1 expression are necessary for cell cycle entry of quiescent cells. From this study, we suggest that the generation of ROS mediated by pre-existing Romo1 protein is required for Myc induction. Meanwhile, Romo1 expression induced by Myc during G1 phase stimulates Skp2-mediated Myc degradation in a negative-feedback mechanism.
In vivo functional analysis reveals specific roles for the integrin-binding sites of talin
Authors: Ellis Stephanie J. , Pines Mary , Fairchild Michael J. , Tanentzapf Guy
Published: May 2011

Adhesion receptors play diverse roles during animal development and require precise spatiotemporal regulation, which is achieved through the activity of their binding partners. Integrins, adhesion receptors that mediate cell attachment to the extracellular matrix (ECM), connect to the intracellular environment through the cytoplasmic adapter protein talin. Talin has two essential functions: orchestrating the assembly of the intracellular adhesion complex (IAC), which associates with integrin, and regulating the affinity of integrins for the ECM. Talin can bind to integrins through two different integrin-binding sites (IBS-1 and IBS-2, respectively). Here, we have investigated the roles of each in the context of Drosophila development. We find that although IBS-1 and IBS-2 are partially redundant, they each have specialized roles during development: IBS-1 reinforces integrin attachment to the ECM, whereas IBS-2 reinforces the link between integrins and the IAC. Disruption of each IBS has different developmental consequences, illustrating how the functional diversity of integrin-mediated adhesion is achieved.
Aerodynamics of tip-reversal upstroke in a revolving pigeon wing
Authors: Crandell Kristen E. , Tobalske Bret W.
Published: May 2011

During slow flight, bird species vary in their upstroke kinematics using either a ‘flexed wing’ or a distally supinated ‘tip-reversal’ upstroke. Two hypotheses have been presented concerning the function of the tip-reversal upstroke. The first is that this behavior is aerodynamically inactive and serves to minimize drag. The second is that the tip-reversal upstroke is capable of producing significant aerodynamic forces. Here, we explored the aerodynamic capabilities of the tip-reversal upstroke using a well-established propeller method. Rock dove (Columba livia, N=3) wings were spread and dried in postures characteristic of either mid-upstroke or mid-downstroke and spun at in vivo Reynolds numbers to simulate forces experienced during slow flight. We compared 3D wing shape for the propeller and in vivo kinematics, and found reasonable kinematic agreement between methods (mean differences 6.4% of wing length). We found that the wing in the upstroke posture is capable of producing substantial aerodynamic forces. At in vivo angles of attack (66 deg at mid-upstroke, 46 deg at mid-downstroke), the upstroke wings averaged for three birds produced a lift-to-drag ratio of 0.91, and the downstroke wings produced a lift-to-drag ratio of 3.33. Peak lift-to-drag ratio was 2.5 for upstroke and 6.3 for downstroke. Our estimates of total force production during each half-stroke suggest that downstroke produces a force that supports 115% of bodyweight, and during upstroke a forward-directed force (thrust) is produced at 36% of body weight.
Mechanisms underlying rhythmic locomotion: dynamics of muscle activation
Authors: Chen Jun , Tian Jianghong , Iwasaki Tetsuya , Friesen W. Otto
Published: May 2011

We have studied the dynamical properties of tension development in leech longitudinal muscle during swimming. A new method is proposed for modeling muscle properties under functionally relevant conditions where the muscle is subjected to both periodic activation and rhythmic length changes. The ‘dual-sinusoid’ experiments were conducted on preparations of leech nerve cord and body wall. The longitudinal muscle was activated periodically by injection of sinusoidal currents into an identified motoneuron. Simultaneously, sinusoidal length changes were imposed on the body wall with prescribed phase differences (12 values equally spaced over 2π radians) with respect to the current injection. Through the singular value decomposition of appropriately constructed tension data matrices, the leech muscle was found to have a multiplicative structure in which the tension was expressed as the product of activation and length factors. The time courses of activation and length factors were determined from the tension data and were used to develop component models. The proposed modeling method is a general one and is applicable to contractile elements for which the effects of series elasticity are negligible.
Seasonal plasticity of auditory hair cell frequency sensitivity correlates with plasma steroid levels in vocal fish
Authors: Rohmann Kevin N. , Bass Andrew H.
Published: May 2011

Vertebrates displaying seasonal shifts in reproductive behavior provide the opportunity to investigate bidirectional plasticity in sensory function. The midshipman teleost fish exhibits steroid-dependent plasticity in frequency encoding by eighth nerve auditory afferents. In this study, evoked potentials were recorded in vivo from the saccule, the main auditory division of the inner ear of most teleosts, to test the hypothesis that males and females exhibit seasonal changes in hair cell physiology in relation to seasonal changes in plasma levels of steroids. Thresholds across the predominant frequency range of natural vocalizations were significantly less in both sexes in reproductive compared with non-reproductive conditions, with differences greatest at frequencies corresponding to call upper harmonics. A subset of non-reproductive males exhibiting an intermediate saccular phenotype had elevated testosterone levels, supporting the hypothesis that rising steroid levels induce non-reproductive to reproductive transitions in saccular physiology. We propose that elevated levels of steroids act via long-term (days to weeks) signaling pathways to upregulate ion channel expression generating higher resonant frequencies characteristic of non-mammalian auditory hair cells, thereby lowering acoustic thresholds.
Striped marsh frog (Limnodynastes peronii) tadpoles do not acclimate metabolic performance to thermal variability
Authors: Niehaus Amanda C. , Wilson Robbie S. , Seebacher Frank , Franklin Craig E.
Published: May 2011

Human-induced climate change is predicted to affect not only the mean temperature of the environment but also the variability and frequency of extreme climatic events. Variability in an organism's developmental environment has the potential to markedly affect an individual's growth trajectory and physiological function, leading to impacts on individual fitness and population dynamics. Thus, it is important to consider the consequences of thermal variability on developing organisms and understand their capacity to respond to such increased variation. We investigated the capacity of larval striped marsh frogs (Limnodynastes peronii) to initiate a response to increases in the thermal variability of their developmental environment by reducing the sensitivity of their physiological rate functions to changes in temperature. In variable environments, we expected the thermal sensitivity of rate functions to decrease and their performance breadth to widen so as to buffer the effect of thermal variability. We raised larvae in stable (24°C), narrowly variable (22–26°C; mean 24°C) and widely variable (14–34°C; mean 24°C) thermal environments and measured the thermal sensitivity of their locomotor performance, heart rate, oxygen consumption and activities of two metabolic enzymes, lactate dehydrogenase and cytochrome c oxidase. We found that the temperature-dependent relationships of these physiological functions did not differ between tadpoles raised in stable or variable thermal conditions. Furthermore, the Q10 values of each response variable were virtually unaffected by treatment when measured over the entire thermal range. Our results reveal that larval amphibians exhibit little plasticity in metabolic traits to thermal variability. This lack of plasticity may have important implications for the growth and population dynamics of organisms in environments that are beginning to experience increased thermal variability.
Fibroblasts from long-lived bird species are resistant to multiple forms of stress
Authors: Harper James M. , Wang Min , Galecki Andrzej T. , Ro Jennifer , Williams Joseph B. , Miller Richard A.
Published: May 2011

Evolutionary senescence theory postulates that aging results from the declining force of natural selection with increasing chronological age. A goal of comparative studies in the biology of aging is to identify genetic and biochemical mechanism(s) driving species-specific differences in the aging process that are the end product of life history trade-offs. We hypothesized that cells from long-lived bird species are more resistant to stress agents than are cells from short-lived species, and that cells from birds are more resistant to stress than are cells from relatively short-lived mammals of similar size. We tested primary fibroblast cultures from 35 species of free-living birds for their resistance to multiple forms of cellular stress and found that cell lines from longer-lived species were resistant to death caused by cadmium (R2=0.27, P=0.002), paraquat (R2=0.13, P=0.03), hydrogen peroxide (R2=0.09, P=0.07) and methyl methanesulfonate (R2=0.13, P=0.03), as well as to the metabolic inhibition seen in low-glucose medium (R2=0.37, P<0.01). They did not differ in their resistance to UV radiation, or to thapsigargin or tunicamycin, inducers of the unfolded protein response. These results were largely consistent even after accounting for the influence of body mass and phylogeny. Cell lines from longer-lived bird species also proliferate more rapidly than cells from short-lived birds, although there was no relationship between proliferation and stress resistance. Finally, avian fibroblasts were significantly more resistant than rodent fibroblasts to each of the tested stressors. These results support the idea that cellular resistance to injury may be an important contributor to the evolution of slow aging and long lifespan among bird species, and may contribute to the relatively long lifespan of birds compared with rodents of the same body size.
Proteomic response to elevated PCO2 level in eastern oysters, Crassostrea virginica: evidence for oxidative stress
Authors: Tomanek Lars , Zuzow Marcus J. , Ivanina Anna V. , Beniash Elia , Sokolova Inna M.
Published: May 2011

Estuaries are characterized by extreme fluctuations in CO2 levels due to bouts of CO2 production by the resident biota that exceed its capacity of CO2 consumption and/or the rates of gas exchange with the atmosphere and open ocean waters. Elevated partial pressures of CO2 (PCO2; i.e. environmental hypercapnia) decrease the pH of estuarine waters and, ultimately, extracellular and intracellular pH levels of estuarine organisms such as mollusks that have limited capacity for pH regulation. We analyzed proteomic changes associated with exposure to elevated PCO2 in the mantle tissue of eastern oysters (Crassostrea virginica) after 2 weeks of exposure to control (∼39 Pa PCO2) and hypercapnic (∼357 Pa PCO2) conditions using two-dimensional gel electrophoresis and tandem mass spectrometry. Exposure to high PCO2 resulted in a significant proteome shift in the mantle tissue, with 12% of proteins (54 out of 456) differentially expressed under the high PCO2 compared with control conditions. Of the 54 differentially expressed proteins, we were able to identify 17. Among the identified proteins, two main functional categories were upregulated in response to hypercapnia: those associated with the cytoskeleton (e.g. several actin isoforms) and those associated with oxidative stress (e.g. superoxide dismutase and several peroxiredoxins as well as the thioredoxin-related nucleoredoxin). This indicates that exposure to high PCO2 (∼357 Pa) induces oxidative stress and suggests that the cytoskeleton is a major target of oxidative stress. We discuss how elevated CO2 levels may cause oxidative stress by increasing the production of reactive oxygen species (ROS) either indirectly by lowering organismal pH, which may enhance the Fenton reaction, and/or directly by CO2 interacting with other ROS to form more free radicals. Although estuarine species are already exposed to higher and more variable levels of CO2 than other marine species, climate change may further increase the extremes and thereby cause greater levels of oxidative stress.
Syntheses of High Molecular Weight Poly(l-phenyllactic acid)s by a Direct Polycondensation in the Presence of Stable Lewis Acids
Authors: Nguyen Hieu Duc , Jin Xin , Kaneko Daisaku , Kaneko Tatsuo
Published: May 2011

Poly(l-phenyllactic acid)s (PlPhLAs) with high molecular weight were prepared by a direct polycondensation of l-phenyllactic acid in the presence of stable Lewis acids such as HfCl4·2THF under various reaction conditions. As a result, PlPhLAs with a number-average molecular weight (Mn) more than 100000 g mol−1 were obtained and showed specific optical rotation [α ]D25 of −46° and the glass-transition temperature (Tg) of 55 °C whose absolute values were higher than the reported values and was comparable with Tg of poly(l-lactic acid).
Synthesis and Characterization of Surface-modified FePt Nanocrystals by Supercritical Hydrothermal Method
Authors: Arita Toshihiko , Hitaka Hidetsugu , Minami Kimitaka , Naka Takashi , Adschiri Tadafumi
Published: May 2011

We have synthesized single nanosized FePt nanocrystals (NCs) by supercritical (sc-) hydrothermal synthesis. The synthesized FePt NCs were characterized by X-ray diffraction (XRD), transmission electron micrography (TEM), electron diffraction (ED), superconducting quantum interference device magnetometry (SQUID), and Fourier transform infrared spectroscopy (FTIR). Surface modification with oleic acid was also successful, and it gave spherical FePt NCs that had average particle size (APS) of 5.0 ± 1.5 nm. In addition, the surface-modified FePt NCs showed good dispersition into organic solvents. A dispersion in tetrahydrofuran (THF) was stable for at least 3 days. The dried surface-modified FePt NCs were easily oxidized in the atmosphere. This high reactivity to oxygen makes the characterization difficult and, at the same time, may indicate that quite a small amount of Fe NC is included in the reaction products.
Combined Molecular Genetic and Cytogenetic Analysis from Single Cells after Isothermal Whole-Genome Amplification
Authors: Kroneis Thomas , Geigl Jochen B , El-Heliebi Amin , Auer Martina , Ulz Peter , Schwarzbraun Thomas , Dohr Gottfried , Sedlmayr Peter
Published: May 2011

BACKGROUND

Analysis of chromosomal aberrations or single-gene disorders from rare fetal cells circulating in the blood of pregnant women requires verification of the cells' genomic identity. We have developed a method enabling multiple analyses at the single-cell level that combines verification of the genomic identity of microchimeric cells with molecular genetic and cytogenetic diagnosis.

METHODS

We used a model system of peripheral blood mononuclear cells spiked with a colon adenocarcinoma cell line and immunofluorescence staining for cytokeratin in combination with DNA staining with the nuclear dye TO-PRO-3 in a preliminary study to define candidate microchimeric (tumor) cells in Cytospin preparations. After laser microdissection, we performed low-volume on-chip isothermal whole-genome amplification (iWGA) of single and pooled cells.

RESULTS

DNA fingerprint analysis of iWGA aliquots permitted successful identification of all analyzed candidate microchimeric cell preparations (6 samples of pooled cells, 7 samples of single cells). Sequencing of 3 single-nucleotide polymorphisms was successful at the single-cell level for 20 of 32 allelic loci. Metaphase comparative genomic hybridization (mCGH) with iWGA products of single cells showed the gains and losses known to be present in the genomic DNA of the target cells.

CONCLUSIONS

This method may be instrumental in cell-based noninvasive prenatal diagnosis. Furthermore, the possibility to perform mCGH with amplified DNA from single cells offers a perspective for the analysis of nonmicrochimeric rare cells exhibiting genomic alterations, such as circulating tumor cells.
Antineuronal autoantibodies in neurological disorders
Authors: Bürk Katrin
Published: May 2011

Autoantibodies (abs) related to neurological disease are currently classified into two large groups depending on the site of the respective target antigen: Group I encompasses abs that recognise intracellular antigens (Hu, Yo, Ri, CV2/CRMP5, amphiphysin, Ma2, SOX, ZIC, GAD, adenylate kinase 5, homer 3), whereas group II abs are targeted against neuronal cell membrane antigens (VGKC, AMPA-R, GABAB-R, NMDA-R, Glycine-R, VGCC, metabotropic GluR1). Both abs groups can be further subdivided according to their diagnostic impact for paraneoplastic or non-paraneoplastic neurological disease. The review gives an overview of the common characteristics of each group and provides more detailed information on single abs and the associated clinical syndromes.
It's a loop world – single strands in RNA as structural and functional elements
Authors: Schudoma Christian
Published: May 2011

Unpaired regions in RNA molecules – loops – are centrally involved in defining the characteristic three-dimensional (3D) architecture of RNAs and are of high interest in RNA engineering and design. Loops adopt diverse, but specific conformations stabilised by complex tertiary structural interactions that provide structural flexibility to RNA structures that would otherwise not be possible if they only consisted of the rigid A-helical shapes usually formed by canonical base pairing. By participating in sequence-non-local contacts, they furthermore contribute to stabilising the overall fold of RNA molecules. Interactions between RNAs and other nucleic acids, proteins, or small molecules are also generally mediated by RNA loop structures. Therefore, the function of an RNA molecule is generally dependent on its loops. Examples include intermolecular interactions between RNAs as part of the microRNA processing pathways, ribozymatic activity, or riboswitch-ligand interactions. Bioinformatics approaches have been successfully applied to the identification of novel RNA structural motifs including loops, local and global RNA 3D structure prediction, and structural and conformational analysis of RNAs and have contributed to a better understanding of the sequence-structure-function relationships in RNA loops.
Pharmacogenetics of the antiepileptic drugs phenytoin and lamotrigine
Authors: López Marisol , Dorado Pedro , Monroy Nancy , Alonso María Elisa , Jung-Cook Helgi , Machín Esther , Peñas-Lledó Eva , Llerena Adrián
Published: May 2011

Patients treated with antiepileptic drugs can exhibit large interindividual variability in clinical efficacy or adverse effects. This could be partially due to genetic variants in genes coding for proteins that function as drug metabolizing enzymes, drug transporters or drug targets. The purpose of this article is to provide an overview of the current knowledge on the pharmacogenetics of two commonly prescribed antiepileptic drugs with similar mechanisms of action; phenytoin (PHT) and lamotrigine (LTG). These two drugs have been selected in order to model the pharmacogenetics of Phase I and Phase II metabolism for PHT and LTG, respectively. In light of the present evidence, patients treated with PHT could benefit fromCYP2C9andCYP2C19genotyping/phenotyping. For those under treatment with LTG,UGT1A4andUGT2B7genotyping might be of clinical use and could contribute to the interindividual variability in LTG concentration to dose ratio in epileptic patients.
Die Suggestion der Theorie – Satzmodus-(In)Kongruenz bei Parenthesen
Authors: Fortmann Christian
Published: May 2011

Parenthetical constructions in German like der Minister des Inneren leidet, (so) sagt man/wie man sagt, an Paranoia are subject to certain restrictions if the host clause is an interrogative and the verb of the reduced parenthetical selects a declarative complement clause: ??wen hat, so glaubt Theo, Franz beleidigt?. According to a quite common conception, a requirement of sentence mood agreement is responsible for the distributional facts. It is the goal of this article to show that this condition fails to account for the facts. Insertion of a parenthetical into an interrogative host is constrained by conditions on reconstruction of the propositional content of the parenthetical's silent complement. In the case of non-agreement, three different types of reduced parentheticals have to be considered in German: verbfirst, so- and wie-parentheticals, which slightly differ with respect to their insertion into an interrogative host. The presuppositon of the interrogative host has to provide for the content of a V1-parenthetical's complement. In so-parentheticals the Adverb so introduces reference to the form of the host, which must be compatible with the canonical form of the verb's complement. wie-parentheticals function as free relative adverbial clauses that constitute a comparative modification of both the host and the parenthetical. Finally, person specification comes into play as an independent factor.
Anmerkungen zur (Un-)Integriertheit von Konditionalsätzen mit Verberststellung
Authors: Pittner Karin
Published: May 2011

Recently, it has been argued that verb-first (V1) conditionals are not, as traditionally assumed, integrated into their matrix clauses, but (quasi-)paratactically adjoined to their host clause (Axel & Wöllstein, German verb-first conditionals as unintegrated clauses. A case study in converging synchronic and diachronic evidence, Mouton de Gruyter, 2009 and Reis & Wöllstein, Zeitschrift für Sprachwissenschaft, 29: 111–179, 2010). As a consequence, the host clause of a left-peripheral V1-conditional clause is considered to be either a V1-declarative sentence or an elliptical V2-declarative sentence. The authors argue with semantic and syntactic properties of V1-clauses and also present diachronic evidence for their views. It is the aim of this paper to take a close look at their arguments in order to show that some do not withstand close scrutiny and that some of the facts presented are at least compatible with other interpretations.
How Does Your Cortex Grow?
Authors: Raznahan Armin , Shaw Phillip , Lalonde Francois , Stockman Mike , Wallace Gregory L. , Greenstein Dede , Clasen Liv , Gogtay Nitin , Giedd Jay N.
Published: May 2011

Understanding human cortical maturation is a central goal for developmental neuroscience. Significant advances toward this goal have come from two recent strands ofin vivostructural magnetic resonance imaging research: (1) longitudinal study designs have revealed that factors such as sex, cognitive ability, and disease are often better related to variations in the tempo of anatomical change than to variations in anatomy at any one time point; (2) largely cross-sectional applications of new surface-based morphometry (SBM) methods have shown how the traditional focus on cortical volume (CV) can obscure information about the two evolutionarily and genetically distinct determinants of CV: cortical thickness (CT) and surface area (SA). Here, by combining these two strategies for the first time and applying SBM in >1250 longitudinally acquired brain scans from 647 healthy individuals aged 3–30 years, we deconstruct cortical development to reveal that distinct trajectories of anatomical change are hidden within, and give rise to, a curvilinear pattern of CV maturation. Developmental changes in CV emerge through the sexually dimorphic and age-dependent interaction of changes in CT and SA. Moreover, SA change itself actually reflects complex interactions between brain size-related changes in exposed cortical convex hull area, and changes in the degree of cortical gyrification, which again vary by age and sex. Knowing of these developmental dissociations, and further specifying their timing and sex-biases, provides potent new research targets for basic and clinical neuroscience.