bluuebunny/crossref_metadata_2025 huggingface dataset:
Adolescent Stress–Induced Epigenetic Control of Dopaminergic Neurons via Glucocorticoids
Authors: Niwa Minae , Jaaro-Peled Hanna , Tankou Stephanie , Seshadri Saurav , Hikida Takatoshi , Matsumoto Yurie , Cascella Nicola G. , Kano Shin-ichi , Ozaki Norio , Nabeshima Toshitaka , Sawa Akira
Published: January 2013

Defeat, Distress, and Glucocorticoids

Understanding how individuals control emotions and cope with stressful events is a major clinical concern and of importance for the treatment of psychiatric illnesses (see the Perspective by

McEwen

).

Barik
et al.

(p.
332
) discovered that aggressive defeat stress in mice caused glucocortioid release and increased activity in the dopamine system. Deleting the glucocorticoid receptors in dopaminoceptive neurons completely prevented the social avoidance that usually follows aggressive defeat. How the combination of genetic factors and environmental stressors during adolescence determines adult behavior and how their disturbance results in neuropsychiatric disorders is poorly understood.

Niwa
et al.

(p.
335
) found that isolation stress during adolescence, which does not cause any long-lasting changes in wild-type mice, induced significant neurochemical and behavioral alterations in mutant mice expressing a dominant-negative variant of the
disrupted in schizophrenia 1
gene under the control of the prion protein promoter. These deficits could be reversed by a glucocorticoid receptor antagonist.
Interstitial Dendritic Cell Guidance by Haptotactic Chemokine Gradients
Authors: Weber Michele , Hauschild Robert , Schwarz Jan , Moussion Christine , de Vries Ingrid , Legler Daniel F. , Luther Sanjiv A. , Bollenbach Tobias , Sixt Michael
Published: January 2013

A Well-Defined Path

Although chemokines have long been thought to direct immune cell movements within tissues, a formal in vivo demonstration and detailed understanding are lacking. By tracking dendritic cell movements in the ears of mice,

Weber
et al.

(p.
328
) were able to provide both. Endogenous gradients of the chemokine CCL21 were observed in ear tissue and, at distances of up 90 µm, dendritic cells were able to use these gradients to migrate directionally toward lymphatic vessels. The CCL21 gradient was immobilized on heparan sulfates and disruption of the gradient inhibited dendritic cell migration.
Comment on "Radiative Absorption Enhancements Due to the Mixing State of Atmospheric Black Carbon"
Authors: Jacobson Mark Z.
Published: January 2013

Cappa
et al
. (Reports, 31 August 2012, p. 1078) suggest that black carbon (BC) in a mixture absorbs only ~6% more sunlight than when volatile chemicals are evaporated from the mixture, and state that "many climate models may overestimate warming by BC." However, the authors misinterpret at least some model results and omit optical focusing at high relative humidity and of involatile components. Thus, their conclusion about model error is not demonstrated.
From Simple Rules Repeated
The Fractalist
Memoir of a Scientific Maverick

by Benoit B. Mandelbrot

Pantheon, New York, 2012. 353 pp. $30, C$35, £18.74. ISBN 9780307377357.
Authors: Finegold Brie
Published: January 2013

In this autobiography, Mandelbrot sketches the mathematical, historical, and personal contexts of his accomplishments.
Killings Force Rethinking of Pakistan's Anti-Polio Drive
Authors: Roberts Leslie
Published: January 2013

What's next for Pakistan's polio vaccination campaign after workers are killed in multiple attacks?
The Promise and Perils of Oxytocin
Authors: Miller Greg
Published: January 2013

Is oxytocin the next revolution in psychiatric medicine—or an overhyped hormone that could make some patients worse?
Atypical Presentation of West Nile Virus in a Newly Diagnosed Human Immunodeficiency Virus Patient in New York City
Authors: Josekutty Joby , Yeh Richard , Mathew Sheena , Ene Ada , Ramessar Nina , Trinidad Jennilee
Published: January 2013

Central nervous system manifestations of West Nile virus (WNV) infection include meningitis, encephalitis, and poliomyelitis-like syndrome. We describe a 44-year-old man with no past medical history who presented with a meningoencephalitic syndrome and spastic paralysis bilaterally in the upper and lower extremities, hyperreflexia, and myoclonus and was ultimately diagnosed as being infected with HIV and WNV.
Molecular Characterization of High-Level-Cholera-Toxin-Producing El Tor Variant Vibrio cholerae Strains in the Zanzibar Archipelago of Tanzania
Authors: Naha A. , Chowdhury G. , Ghosh-Banerjee J. , Senoh M. , Takahashi T. , Ley B. , Thriemer K. , Deen J. , Seidlein L. V. , Ali S. M. , Khatib A. , Ramamurthy T. , Nandy R. K. , Nair G. B. , Takeda Y. , Mukhopadhyay A. K.
Published: January 2013

Analysis of 1,180 diarrheal stool samples in Zanzibar detected 247
Vibrio cholerae
O1, Ogawa strains in 2009. Phenotypic traits and PCR-based detection of
rstR
,
rtxC
, and
tcpA
alleles showed that they belonged to the El Tor biotype. Genetic analysis of
ctxB
of these strains revealed that they were classical type, and production of classical cholera toxin B (CTB) was confirmed by Western blotting. These strains produced more CT than the prototype El Tor and formed a separate cluster by pulsed-field gel electrophoresis (PFGE) analysis.
Quantitative Real-Time PCR Assay Panel for Detection and Type-Specific Identification of Epidemic Respiratory Human Adenoviruses
Authors: Lu Xiaoyan , Trujillo-Lopez Elizabeth , Lott Lisa , Erdman Dean D.
Published: January 2013

Outbreaks of human adenovirus (HAdV) acute respiratory illness (ARI) have been well documented among civilians and unvaccinated military recruits. Among the 7 recognized HAdV species (A to G), species B (particularly serotypes 3, 7, 11, 14, and 21) and E (serotype 4) have more often been associated with epidemic ARI. Rapid detection and type-specific identification of these viruses would enhance outbreak response and help guide prevention and control measures. To this end, we developed type-specific real-time quantitative PCR (qPCR) assays for HAdV types 3, 4, 7, 11, 14, 16, and 21 targeting the HAdV hexon gene. All type-specific qPCR assays reproducibly detected as few as 10 copies/reaction of quantified hexon recombinant plasmids with a linear dynamic range of 8 log units (10
1
to 10
8
copies); in contrast, a generic qPCR assay that detects all HAdV types run concurrently detected between 10 and 100 copies/reaction, depending on the virus type. No nonspecific amplifications were observed with concentrated nucleic acid from 51 HAdV prototype strains or other common respiratory pathogens. All members of a panel of 137 previously typed HAdV field isolates and positive clinical specimens were correctly characterized by the type-specific qPCR assays; two different HAdV types were detected in three of the clinical specimens and confirmed by amplicon sequencing. The qPCR assays permit sensitive, specific, and quantitative detection and identification of seven clinically important respiratory HAdVs and should provide a convenient adjunct to classical typing methods for a rapid response to HAdV outbreaks.
Alterations in the MA and NC Domains Modulate Phosphoinositide-Dependent Plasma Membrane Localization of the Rous Sarcoma Virus Gag Protein
Authors: Nadaraia-Hoke Shorena , Bann Darrin V. , Lochmann Timothy L. , Gudleski-O'Regan Nicole , Parent Leslie J.
Published: January 2013

Retroviral Gag proteins direct virus particle assembly from the plasma membrane (PM). Phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P
2
] plays a role in PM targeting of several retroviral Gag proteins. Here we report that depletion of intracellular PI(4,5)P
2
and phosphatidylinositol-(3,4,5)-triphosphate [PI(3,4,5)P
3
] levels impaired Rous sarcoma virus (RSV) Gag PM localization. Gag mutants deficient in nuclear trafficking were less sensitive to reduction of intracellular PI(4,5)P
2
and PI(3,4,5)P
3
, suggesting a possible connection between Gag nuclear trafficking and phosphoinositide-dependent PM targeting.
The Large Groove Found in the gH/gL Structure Is an Important Functional Domain for Epstein-Barr Virus Fusion
Authors: Chen Jia , Jardetzky Theodore S. , Longnecker Richard
Published: January 2013

Epstein-Barr virus (EBV) mediates viral entry into cells using four glycoproteins—gB, the gH/gL complex, and gp42—and fusion is cell type specific. gB and gH/gL are required for epithelial cell fusion; B cell fusion also requires gp42. To investigate functional domains within the gH/gL structure, we constructed site-directed EBV gH/gL mutants with alterations of residues located in a large groove that separates domain I (D-I) from domain II (D-II) within the gH/gL structure. We found that substitution of alanine for leucine 207 reduces both epithelial and B cell fusion and is accompanied by reduced gp42 binding. We also observed that substitution of alanine for arginine 152, histidine 154, or threonine 174 reduces fusion with epithelial cells but not with B cells. To test whether flexibility of the region between D-I and D-II of gH/gL could be important for membrane fusion activity and to allow potential interactions across the D-I/D-II groove, we mutated D-I amino acids V47, P48, and G49 to cysteine, allowing novel intersubunit disulfide bonds to form with the free C153 located in D-II. We found that the G49C mutant, predicted to bridge D-I and D-II with C153 of gH/gL, had normal B cell fusion activity but reduced epithelial cell fusion activity, which was partially restored by treatment with dithiothreitol. We conclude that structural rearrangements and/or interactions across the D-I/D-II groove of gH/gL are required for fusion with epithelial cells but not for fusion with B cells.
Reevaluation of the Requirement for TIP47 in Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Incorporation
Authors: Checkley Mary Ann , Luttge Benjamin G. , Mercredi Peter Y. , Kyere Sampson K. , Donlan Justin , Murakami Tsutomu , Summers Michael F. , Cocklin Simon , Freed Eric O.
Published: January 2013

Incorporation of the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins into assembling particles is crucial for virion infectivity. Genetic and biochemical data indicate that the matrix (MA) domain of Gag and the cytoplasmic tail of the transmembrane glycoprotein gp41 play an important role in coordinating Env incorporation; however, the molecular mechanism and possible role of host factors in this process remain to be defined. Recent studies suggested that Env incorporation is mediated by interactions between matrix and tail-interacting protein of 47 kDa (TIP47; also known as perilipin-3 and mannose-6-phosphate receptor-binding protein 1), a member of the perilipin, adipophilin, TIP47 (PAT) family of proteins implicated in protein sorting and lipid droplet biogenesis. We have confirmed by nuclear magnetic resonance spectroscopy titration experiments and surface plasmon resonance that MA binds TIP47. We also reevaluated the role of TIP47 in HIV-1 Env incorporation in HeLa cells and in the Jurkat T-cell line. In HeLa cells, TIP47 overexpression or RNA interference (RNAi)-mediated depletion had no significant effect on HIV-1 Env incorporation, virus release, or particle infectivity. Similarly, depletion of TIP47 in Jurkat cells did not impair HIV-1 Env incorporation, virus release, infectivity, or replication. Our results thus do not support a role for TIP47 in HIV-1 Env incorporation or virion infectivity.
The impact of the built environment on health across the life course: design of a cross-sectional data linkage study
Authors: Villanueva Karen , Pereira Gavin , Knuiman Matthew , Bull Fiona , Wood Lisa , Christian Hayley , Foster Sarah , Boruff Bryan J , Beesley Bridget , Hickey Sharyn , Joyce Sarah , Nathan Andrea , Saarloos Dick , Giles-Corti Billie
Published: January 2013

Introduction

The built environment is increasingly recognised as being associated with health outcomes. Relationships between the built environment and health differ among age groups, especially between children and adults, but also between younger, mid-age and older adults. Yet few address differences across life stage groups within a single population study. Moreover, existing research mostly focuses on physical activity behaviours, with few studyingobjectiveclinical and mental health outcomes. The Life Course Built Environment and Health (LCBEH) project explores the impact of the built environment on self-reported and objectively measured health outcomes in a random sample of people across the life course.

Methods and analysis

This cross-sectional data linkage study involves 15 954 children (0–15 years), young adults (16–24 years), adults (25–64 years) and older adults (65+years) from the Perth metropolitan region who completed the Health and Wellbeing Surveillance System survey administered by the Department of Health of Western Australia from 2003 to 2009. Survey data were linked to Western Australia's (WA) Hospital Morbidity Database System (hospital admission) and Mental Health Information System (mental health system outpatient) data. Participants’ residential address was geocoded and features of their ‘neighbourhood’ were measured using Geographic Information Systems software. Associations between the built environment and self-reported and clinical health outcomes will be explored across varying geographic scales and life stages.

Ethics and dissemination

The University of Western Australia's Human Research Ethics Committee and the Department of Health of Western Australia approved the study protocol (#2010/1). Findings will be published in peer-reviewed journals and presented at local, national and international conferences, thus contributing to the evidence base informing the design of healthy neighbourhoods for all residents.
A ROBUST MOVING BODY RECOGNITION METHOD
Authors: WANG SHOUJIA , LI WENHUI , FU BO , NI HONGYIN , WANG CONG
Published: January 2013

At present, moving body recognition is one of the most active areas of research in the field of computer vision and is used widely in all kinds of videos. But the recognition accuracy of these methods has changed negatively because of the complexity of the background. In this paper, we put forward a robust recognition method. First, we obtain the moving body by tripling the temporal difference method. And then we eliminate noise from these images by mathematical morphology. Finally, we use three-scanning notation method to mark and connect the connected domain. This new method is more accurate and requires less computation in real-time experiments. The experiment result also proves its robustness.
Contribution of increased VEGF receptors to hypoxic changes in fetal ovine carotid artery contractile proteins
Authors: Adeoye Olayemi O. , Butler Stacy M. , Hubbell Margaret C. , Semotiuk Andrew , Williams James M. , Pearce William J.
Published: January 2013

Recent studies suggest that vascular endothelial growth factor (VEGF) can modulate smooth muscle phenotype and, consequently, the composition and function of arteries upstream from the microcirculation, where angiogenesis occurs. Given that hypoxia potently induces VEGF, the present study explores the hypothesis that, in fetal arteries, VEGF contributes to hypoxic vascular remodeling through changes in abundance, organization, and function of contractile proteins. Pregnant ewes were acclimatized at sea level or at altitude (3,820 m) for the final 110 days of gestation. Endothelium-denuded carotid arteries from full-term fetuses were used fresh or after 24 h of organ culture in a physiological concentration (3 ng/ml) of VEGF. After 110 days, hypoxia had no effect on VEGF abundance but markedly increased abundance of the Flk-1 (171%) and Flt-1 (786%) VEGF receptors. Hypoxia had no effect on smooth muscle α-actin (SMαA), decreased myosin light chain (MLC) kinase (MLCK), and increased 20-kDa regulatory MLC (MLC20) abundances. Hypoxia also increased MLCK-SMαA, MLC20-SMαA, and MLCK-MLC20 colocalization. Compared with hypoxia, organ culture with VEGF produced the same pattern of changes in contractile protein abundance and colocalization. Effects of VEGF on colocalization were blocked by the VEGF receptor antagonists vatalanib (240 nM) and dasatinib (6.3 nM). Thus, through increases in VEGF receptor density, hypoxia can recruit VEGF to help mediate remodeling of fetal arteries upstream from the microcirculation. The results support the hypothesis that VEGF contributes to hypoxic vascular remodeling through changes in abundance, organization, and function of contractile proteins.
Role of serine-threonine phosphoprotein phosphatases in smooth muscle contractility
Authors: Butler Trent , Paul Jonathan , Europe-Finner Nick , Smith Roger , Chan Eng-Cheng
Published: January 2013

The degree of phosphorylation of myosin light chain 20 (MLC20) is a major determinant of force generation in smooth muscle. Myosin phosphatases (MPs) contain protein phosphatase (PP) 1 as catalytic subunits and are the major enzymes that dephosphorylate MLC20. MP regulatory targeting subunit 1 (MYPT1), the main regulatory subunit of MP in all smooth muscles, is a key convergence point of contractile and relaxatory pathways. Combinations of regulatory mechanisms, including isoform splicing, multiple phosphorylation sites, and scaffolding proteins, modulate MYPT1 activity with tissue and agonist specificities to affect contraction and relaxation. Other members of the PP1 family that do not target myosin, as well as PP2A and PP2B, dephosphorylate a range of proteins that affect smooth muscle contraction. This review discusses the role of phosphatases in smooth muscle contractility with a focus on MYPT1 in uterine smooth muscle. Myometrium shares characteristics of vascular and other visceral smooth muscles yet, during healthy pregnancy, undergoes hypertrophy, hyperplasia, quiescence, and labor as physiological processes. Myometrium presents an accessible model for the study of normal and pathological smooth muscle function, and a better understanding of myometrial physiology may allow the development of novel therapeutics for the many disorders of myometrial physiology from preterm labor to dysmenorrhea.
Physiology of SLC12 transporters: lessons from inherited human genetic mutations and genetically engineered mouse knockouts
Authors: Gagnon Kenneth B. , Delpire Eric
Published: January 2013

Among the over 300 members of the solute carrier (SLC) group of integral plasma membrane transport proteins are the nine electroneutral cation-chloride cotransporters belonging to the SLC12 gene family. Seven of these transporters have been functionally described as coupling the electrically silent movement of chloride with sodium and/or potassium. Although in silico analysis has identified two additional SLC12 family members, no physiological role has been ascribed to the proteins encoded by either the SLC12A8 or the SLC12A9 genes. Evolutionary conservation of this gene family from protists to humans confirms their importance. A wealth of physiological, immunohistochemical, and biochemical studies have revealed a great deal of information regarding the importance of this gene family to human health and disease. The sequencing of the human genome has provided investigators with the capability to link several human diseases with mutations in the genes encoding these plasma membrane proteins. The availability of bacterial artificial chromosomes, recombination engineering techniques, and the mouse genome sequence has simplified the creation of targeting constructs to manipulate the expression/function of these cation-chloride cotransporters in the mouse in an attempt to recapitulate some of these human pathologies. This review will summarize the three human disorders that have been linked to the mutation/dysfunction of the Na-Cl, Na-K-2Cl, and K-Cl cotransporters (i.e., Bartter's, Gitleman's, and Andermann's syndromes), examine some additional pathologies arising from genetically modified mouse models of these cotransporters including deafness, blood pressure, hyperexcitability, and epithelial transport deficit phenotypes.
Differential expression of HCN subunits alters voltage-dependent gating of h-channels in CA1 pyramidal neurons from dorsal and ventral hippocampus
Authors: Dougherty Kelly A. , Nicholson Daniel A. , Diaz Laurea , Buss Eric W. , Neuman Krystina M. , Chetkovich Dane M. , Johnston Daniel
Published: January 2013

The rodent hippocampus can be divided into dorsal (DHC) and ventral (VHC) domains on the basis of behavioral, anatomical, and biochemical differences. Recently, we reported that CA1 pyramidal neurons from the VHC were intrinsically more excitable than DHC neurons, but the specific ionic conductances contributing to this difference were not determined. Here we investigated the hyperpolarization-activated current ( Ih) and the expression of HCN1 and HCN2 channel subunits in CA1 pyramidal neurons from the DHC and VHC. Measurement of Ih with cell-attached patches revealed a significant depolarizing shift in the V1/2 of activation for dendritic h-channels in VHC neurons (but not DHC neurons), and ultrastructural immunolocalization of HCN1 and HCN2 channels revealed a significantly larger HCN1-to-HCN2 ratio for VHC neurons (but not DHC neurons). These observations suggest that a shift in the expression of HCN1 and HCN2 channels drives functional changes in Ih for VHC neurons (but not DHC neurons) and could thereby significantly alter the capacity for dendritic integration of these neurons.
A computational model for optimal muscle activity considering muscle viscoelasticity in wrist movements
Authors: Kambara Hiroyuki , Shin Duk , Koike Yasuharu
Published: January 2013

To understand the mechanism of neural motor control, it is important to clarify how the central nervous system organizes the coordination of redundant muscles. Previous studies suggested that muscle activity for step-tracking wrist movements are optimized so as to reduce total effort or end-point variance under neural noise. However, since the muscle dynamics were assumed as a simple linear system, some characteristic patterns of experimental EMG were not seen in the simulated muscle activity of the previous studies. The biological muscle is known to have dynamic properties in which its elasticity and viscosity depend on activation level. The motor control system is supposed to consider the viscoelasticity of the muscles when generating motor command signals. In this study, we present a computational motor control model that can control a musculoskeletal system with nonlinear dynamics. We applied the model to step-tracking wrist movements actuated by five muscles with dynamic viscoelastic properties. To solve the motor redundancy, we designed the control model to generate motor commands that maximize end-point accuracy under signal-dependent noise, while minimizing the squared sum of them. Here, we demonstrate that the muscle activity simulated by our model exhibits spatiotemporal features of experimentally observed muscle activity of human and nonhuman primates. In addition, we show that the movement trajectories resulting from the simulated muscle activity resemble experimentally observed trajectories. These results suggest that, by utilizing inherent viscoelastic properties of the muscles, the neural system may optimize muscle activity to improve motor performance.
Performance monitoring by presupplementary and supplementary motor area during an arm movement countermanding task
Authors: Scangos Katherine W. , Aronberg Ryan , Stuphorn Veit
Published: January 2013

A key component of executive control and decision making is the ability to use the consequences of chosen actions to update and inform the process of future action selection. Evaluative signals, which monitor the outcomes of actions, are critical for this ability. Signals related to the evaluation of actions have been identified in eye movement-related areas of the medial frontal cortex. Here we examined whether such evaluative signals are also present in areas of the medial frontal cortex related to arm movements. To answer this question, we recorded from cells in the supplementary motor area (SMA) and pre-SMA, while monkeys performed an arm movement version of the countermanding paradigm. SMA and pre-SMA have been implicated in the higher-order control of movement selection and execution, although their precise role within the skeletomotor control circuit is unclear. We found evaluative signals that encode information about the expected outcome of the reward, the actual outcome, and the mismatch between actual and intended outcome. These findings suggest that signals that monitor and evaluate movement outcomes are represented throughout the medial frontal cortex, playing a general role across effector systems. These evaluation signals supervise the relationship between intentional motor behavior and reward expectation and could be used to adaptively shape future goal-directed behavior.
Does risk-sensitivity transfer across movements?
Authors: O'Brien Megan K. , Ahmed Alaa A.
Published: January 2013

An intriguing finding in motor control studies is the marked effect of risk on movement decision making. However, there are inconsistent reports of risk-sensitivity across different movements and tasks, with both risk-seeking and risk-averse behavior observed. This raises the question of whether risk-sensitivity in movement decision making is context dependent and specific to the movement or task being performed. We investigated whether risk-sensitivity transfers between dissimilar movements within a single task. Healthy young adults made arm-reaching movements or whole-body leaning movements to move a cursor as close to the edge of a virtual cliff as possible without moving beyond the edge. They received points on the basis of the cursor's final proximity to the cliff edge. Risk was manipulated by increasing the point penalty associated with the cliff region and/or adding Gaussian noise to the cursor. We compared subjects' movement endpoints with endpoints predicted by a subject-specific, risk-neutral model of movement planning. Subjects demonstrated risk-seeking behavior in both movements that was consistent across risk environments, moving closer to the cliff than the model predicted. However, subjects were significantly more risk-seeking in whole-body movements. Our results present the first evidence of risk-sensitivity in whole-body movements. They also demonstrate that the direction of risk-sensitivity (i.e., risk-seeking or risk-averse) is similar between arm-reaching and whole-body movements, although degree of risk-sensitivity did not transfer from one movement to another. This finding has important implications for the ability of quantitative descriptions of decision making to generalize across movements and, ultimately, decision-making contexts.
Connections between expiratory bulbospinal neurons and expiratory motoneurons in thoracic and upper lumbar segments of the spinal cord
Authors: Road J. D. , Ford T. W. , Kirkwood P. A.
Published: January 2013

Cross-correlation of neural discharges was used to investigate the connections between expiratory bulbospinal neurons (EBSNs) in the caudal medulla and expiratory motoneurons innervating thoracic and abdominal muscles in anesthetized cats. Peaks were seen in the cross-correlation histograms for around half of the EBSN-nerve pairs for the following: at T8, the nerve branches innervating internal intercostal muscle and external abdominal oblique muscle and a more distal branch of the internal intercostal nerve; and at L1, a nerve branch innervating internal abdominal oblique muscle and a more distal branch of the ventral ramus. Fewer peaks were seen for the L1 nerve innervating external abdominal oblique, but a paucity of presumed α-motoneuron discharges could explain the rarity of the peaks in this instance. Taking into account individual EBSN conduction times to T8 and to L1, as well as peripheral conduction times, nearly all of the peaks were interpreted as representing monosynaptic connections. Individual EBSNs showed connections at both T8 and L1, but without any discernible pattern. The overall strength of the monosynaptic connection from EBSNs at L1 was found to be very similar to that at T8, which was previously argued to be substantial and responsible for the temporal patterns of expiratory motoneuron discharges. However, we argue that other inputs are required to create the stereotyped spatial patterns of discharges in the thoracic and abdominal musculature.
Adipokines, Oxidized Low-Density Lipoprotein, and C-Reactive Protein Levels in Lean, Overweight, and Obese Portuguese Patients with Type 2 Diabetes
Authors: Neuparth Maria João , Proença Jorge Brandão , Santos-Silva Alice , Coimbra Susana
Published: January 2013

Aim. Our aim was to study how different BMI scores may influence the levels of inflammation, oxidative stress, adipogenesis, glucose, and lipid metabolism, in lean, overweight, and obese Portuguese patients with type 2 diabetes mellitus (T2DM). Methods. We studied 28 lean, 38 overweight, and 17 obese patients with T2DM and 20 controls (gender and age matched). The circulating levels of oxLDL, CRP, and some adipokines—adiponectin, leptin, and chemerin—and the lipid profile were evaluated. Results. Obese patients presented significantly lower levels of adiponectin and higher leptin, oxLDL, and chemerin levels, as compared to the overweight, lean, and control groups. Overweight, compared to lean and control, subjects showed significantly lower adiponectin and higher leptin and chemerin levels; oxLDL values were significantly higher in overweight than in lean patients. Lean patients presented significantly higher chemerin values than the control. Obese patients presented significantly higher CRP values, as compared to lean patients and the control group. Obese and overweight patients presented significantly higher triglycerides values than lean patients. Except for CRP, all the observed significant changes between control and patients remained significant after statistical adjustment for the body mass index (BMI). Conclusion. The levels of leptin, adiponectin, oxLDL, CRP, and triglycerides in patients with T2DM seem to be more associated with obesity and less with diabetes. Chemerin levels were raised in lean, overweight, and obese patients, suggesting that, independently of BMI, an adipocyte dysfunction occurs. Moreover, chemerin may provide an important early biomarker of adipocyte dysfunction and a link between obesity and type 2 diabetes mellitus.
A Mathematical Model for Thermosensitive Liposomal Delivery of Doxorubicin to Solid Tumour
Authors: Zhan Wenbo , Xu Xiao Yun
Published: January 2013

The effectiveness of anticancer treatments is often hampered by the serious side effects owing to toxicity of anticancer drugs and their undesirable uptake by healthy cells in vivo. Thermosensitive liposome-mediated drug delivery has been developed as part of research efforts aimed at improving therapeutic efficacy while reducing the associated side effect. Since multiple steps are involved in the transport of drug-loaded liposomes, drug release, and its uptake, mathematical models become an indispensible tool to analyse the transport processes and predict the outcome of anticancer treatment. In this study, a computational model is developed which incorporates the key physical and biochemical processes involved in drug delivery and cellular uptake. The model has been applied to idealized tumour geometry, and comparisons are made between continuous infusion of doxorubicin and thermosensitive liposome-mediated delivery. Results show that thermosensitive liposome-mediated delivery performs better in reducing drug concentration in normal tissues, which may help lower the risk of associated side effects. Compared with direct infusion over a 2-hour period, thermosensitive liposome delivery leads to a much higher peak intracellular concentration of doxorubicin, which may increase cell killing in tumour thereby enhancing the therapeutic effect of the drug.
MHD Flow and Heat Transfer in a Channel Bounded by a Shrinking Sheet and a Porous Medium Bed: Homotopy Analysis Method
Authors: Chauhan Dileep Singh , Agrawal Rashmi
Published: January 2013

MHD flow of viscous conducting fluid is considered between a shrinking sheet and a porous medium bed. Suction is applied at the upper shrinking sheet and its surface temperature is always maintained higher than the temperature of the lower porous bed surface. Similarity transformations and HAM are used to solve the governing equations for velocity and temperature fields. The effects of various pertinent parameters on the results are discussed graphically.
Energy- and Regularity-Dependent Stability Estimates for Near-Field Inverse Scattering in Multidimensions
Authors: Isaev M. I.
Published: January 2013

We prove new global Hölder-logarithmic stability estimates for the near-field inverse scattering problem in dimensiond≥3. Our estimates are given in uniform norm for coefficient difference and related stability efficiently increases with increasing energy and/or coefficient regularity. In addition, a global logarithmic stability estimate for this inverse problem in dimensiond=2is also given.
Rodent Carcinogenicity Dataset
Authors: Fjodorova Natalja , Novič Marjana
Published: January 2013

The rodent carcinogenicity dataset was compiled from the Carcinogenic Potency Database (CPDBAS) and was applied for the classification of quantitative structure‐activity relationship (QSAR) models for the prediction of carcinogenicity based on the counter‐propagation artificial neural network (CP ANN) algorithm. The models were developed within EU‐funded project CAESAR for regulatory use. The dataset contains the following information: common information about chemicals (ID, chemical name, and their CASRN), molecular structure information (SDF files and SMILES), and carcinogenic (toxicological) properties information: carcinogenic potency (TD50_Rat_mg; carcinogen/noncarcinogen) and structural alert (SA) for carcinogenicity based on mechanistic data. Molecular structure information was used to get chemometrics information to calculate molecular descriptors (254 MDL and 784 Dragon descriptors), which were further used in predictive QSAR modeling. The dataset presented in the paper can be used in future research in oncology, ecology, or chemicals′ risk assessment.
Effect of Citrus Byproducts on Survival of O157:H7 and Non-O157Escherichia coliSerogroups withinIn VitroBovine Ruminal Microbial Fermentations
Authors: Duoss-Jennings Heather A. , Schmidt Ty B. , Callaway Todd R. , Carroll Jeffery A. , Martin James M. , Shields-Menard Sara A. , Broadway Paul R. , Donaldson Janet R.
Published: January 2013

Citrus byproducts (CBPs) are utilized as a low cost nutritional supplement to the diets of cattle and have been suggested to inhibit the growth of bothEscherichia coliO157:H7 andSalmonella. The objective of this study was to examine the effectsin vitrothat varying concentrations of CBP in the powdered or pelleted variety have on the survival of Shiga-toxinEscherichia coli(STEC) serotypes O26:H11, O103:H8, O111:H8, O145:H28, and O157:H7 in bovine ruminal microorganism media. The O26:H11, O111:H8, O145:H28, and O157:H7 serotypes did not exhibit a change in populations in media supplemented with CBP with either variety. The O103:H8 serotype displayed a general trend for an approximate1log10reduction in 5% powdered CBP and 20% pelleted CBP over 6 h. There was a trend for reductions in populations of a variant form of O157:H7 mutated in thestx1 andstx2 genes in higher concentrations of CBP. These results suggest that variations exist in the survival of these serotypes of STEC within mixed ruminal microorganism fluid media when supplemented with CBP. Further research is needed to determine why CBPs affect STEC serotypes differently.
In Vivo Tracking of Murine Adipose Tissue-Derived Multipotent Adult Stem Cells and Ex Vivo Cross-Validation
Authors: Garrovo Chiara , Bergamin Natascha , Bates Dave , Cesselli Daniela , Beltrami Antonio Paolo , Lorenzon Andrea , Ferrari Roberto , Alberto Beltrami Carlo , Lorusso Vito , Biffi Stefania
Published: January 2013

Stem cells are characterized by the ability to renew themselves and to differentiate into specialized cell types, while stem cell therapy is believed to treat a number of different human diseases through either cell regeneration or paracrine effects. Herein, an in vivo and ex vivo near infrared time domain (NIR TD) optical imaging study was undertaken to evaluate the migratory ability of murine adipose tissue-derived multipotent adult stem cells [mAT-MASC] after intramuscular injection in mice. In vivo NIR TD optical imaging data analysis showed a migration of DiD-labelled mAT-MASC in the leg opposite the injection site, which was confirmed by a fibered confocal microendoscopy system. Ex vivo NIR TD optical imaging results showed a systemic distribution of labelled cells. Considering a potential microenvironmental contamination, a cross-validation study by multimodality approaches was followed: mAT-MASC were isolated from male mice expressing constitutively eGFP, which was detectable using techniques of immunofluorescence and qPCR. Y-chromosome positive cells, injected into wild-type female recipients, were detected by FISH. Cross-validation confirmed the data obtained by in vivo/ex vivo TD optical imaging analysis. In summary, our data demonstrates the usefulness of NIR TD optical imaging in tracking delivered cells, giving insights into the migratory properties of the injected cells.
Effects of a Phone Call Intervention to Promote Adherence to Antiretroviral Therapy and Quality of Life of HIV/AIDS Patients in Baoshan, China: A Randomized Controlled Trial
Authors: Huang Dongsheng , Sangthong Rassamee , McNeil Edward , Chongsuvivatwong Virasakdi , Zheng Weibin , Yang Xuemei
Published: January 2013

Background. Suboptimal adherence to antiretroviral therapy (ART) is still pervasive. The effect of using a mobile phone call intervention to improve patient adherence is currently not known.Objective. This study aims to investigate the effects of a phone call intervention on adherence to ART and quality of life (QOL) of treatment-naive and treatment-experienced patients.Methods. A randomized controlled trial was conducted in the three largest public hospitals. Adherence was measured by self-completed questionnaires. QOL was assessed by the WHOQOL-HIV BREF. Outcomes were assessed at day 15, at 1, 2, and 3 months after start of treatment for treatment-naive patients and at 3 months after study enrollment for treatment-experienced patients.Results. A total of 103 treatment-naive and 93 treatment-experienced HIV/AIDS patients were consecutively recruited. Results show that a phone call intervention could maintain high self-reported adherence among both treatment-naive and treatment-experienced patients. After three months, significant QOL improvements were observed in domains of physical health(P=0.003), level of independence(P=0.018), environment(P=0.002), and spirituality/religion/personal beliefs(P=0.021)among treatment-naive patients.Conclusion. A mobile phone call intervention to patients could maintain high adherence rates although no statistically significant differences were found. A phone call could improve some domains of QOL among treatment-naive patients.
Extraesophageal Reflux: What Is the Best Parameter for pH-Monitoring Data Analysis from the Perspective of Patient Response to Proton Pump Inhibitors?
Authors: Zelenik Karol , Matousek Petr , Tedla Miroslav , Syrovatka Jakub , Kominek Pavel
Published: January 2013

Objectives. To analyze the pH-monitoring records of patients with suspected extraesophageal reflux (EER) using three different parameters (number of refluxes (NOR), acid exposure time (AET), and reflux area index (RAI)), with a view to determining which type of analysis is best at selecting the patients who will respond to a proton pump inhibitor (PPI).Methods. Demographic data were obtained and the level of the complaint was assessed using the Visual Analogue Scale. A dual probe pH-monitoring study was conducted. NOR greater than six, AET more than 0.1%, and RAI higher than 6.3 mpH were taken to be the thresholds for EER. Subsequently the response to a 12-week PPI trial was analyzed.Results. A total of 81 patients were analyzed. The percentages of patients with substantial EER based on NOR, AET, and RAI were 36%, 28% and 26%, respectively. Statistically significant, often positive PPI trials were confirmed in the group identified as having substantial EER using all three types of analysis. When using AET and RAI, the significance was more pronounced (P=0.012andP=0.013, resp.) in comparison with NOR (P=0.033).Conclusions. Patients with EER diagnosed using AET or RAI will respond to PPI significantly often.
Exercise and Bone Mineral Density in Premenopausal Women: A Meta-Analysis of Randomized Controlled Trials
Authors: Kelley George A. , Kelley Kristi S. , Kohrt Wendy M.
Published: January 2013

Objective. Examine the effects of exercise on femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD) in premenopausal women.Methods. Meta-analysis of randomized controlled exercise trials ≥24 weeks in premenopausal women. Standardized effect sizes (g) were calculated for each result and pooled using random-effects models,Zscore alpha values, 95% confidence intervals (CIs), and number needed to treat (NNT). Heterogeneity was examined usingQandI2. Moderator and predictor analyses using mixed-effects ANOVA and simple metaregression were conducted. Statistical significance was set atP≤0.05.Results. Statistically significant improvements were found for both FN (7g's, 466 participants,g=0.342, 95%  CI=0.132, 0.553,P=0.001,Q=10.8,P=0.22,I2=25.7%,NNT=5) and LS (6g's, 402 participants,g=0.201, 95%  CI=0.009, 0.394,P=0.04,Q=3.3,P=0.65,I2=0%,NNT=9) BMD. A trend for greater benefits in FN BMD was observed for studies published in countries other than the United States and for those who participated in home versus facility-based exercise. Statistically significant, or a trend for statistically significant, associations were observed for 7 different moderators and predictors, 6 for FN BMD and 1 for LS BMD.Conclusions. Exercise benefits FN and LS BMD in premenopausal women. The observed moderators and predictors deserve further investigation in well-designed randomized controlled trials.
IL-17A in Human Respiratory Diseases: Innate or Adaptive Immunity? Clinical Implications
Authors: Bullens Dominique M. A. , Decraene Ann , Seys Sven , Dupont Lieven J.
Published: January 2013

Since the discovery of IL-17 in 1995 as a T-cell cytokine, inducing IL-6 and IL-8 production by fibroblasts, and the report of a separate T-cell lineage producing IL-17(A), called Th17 cells, in 2005, the role of IL-17 has been studied in several inflammatory diseases. By inducing IL-8 production and subsequent neutrophil attraction towards the site of inflammation, IL-17A can link adaptive and innate immune responses. More specifically, its role in respiratory diseases has intensively been investigated. We here review its role in human respiratory diseases and try to unravel the question whether IL-17A only provides a link between the adaptive and innate respiratory immunity or whether this cytokine might also be locally produced by innate immune cells. We furthermore briefly discuss the possibility to reduce local IL-17A production as a treatment option for respiratory diseases.
A Dual 5α-Reductase Inhibitor Dutasteride Caused Reductions in Vascular Density and Area in Benign Prostatic Hyperplasia
Authors: Zaitsu Masayoshi , Tonooka Akiko , Mikami Koji , Hattori Mami , Takeshima Yuta , Uekusa Toshimasa , Takeuchi Takumi
Published: January 2013

Objectives. Dutasteride, a dual 5α-reductase inhibitor, is used to treat benign prostatic hyperplasia. Nevertheless, its histopathological effects on the morphometrics of blood vessels and glands are still controversial. The aim here was to assess the histopathological effects of dutasteride in cases of benign prostatic hyperplasia in a retrospective study.Methods. Patients with benign prostatic hyperplasia more than 40 cm3in prostatic volume were administered 0.5 mg of dutasteride daily or left untreated prior to receiving a transurethral resection of the prostate. Images of sections stained with hematoxylin/eosin and with anti-CD31 antibody were analyzed.Results. In the dutasteride-treated group, the duration of administration was weeks. Artery/arteriole density and vein/venule density in benign prostatic tissue were both lower in the dutasteride-treated group than in the control group. The vein/venule area as a percentage of the whole area was also lower in the dutasteride-treated group, while the artery/arteriole area did not show a significant difference. Glandular/CD31-expressing vessel densities as well as glandular/CD31-expressing vessel areas were comparable between the two groups.Conclusions. Dutasteride reduced the artery/arteriole and vein/venule densities and the proportion of vein/venule area in the tissue of patients with benign prostatic hyperplasia.
Application of Bait Treated with the Entomopathogenic FungusMetarhizium anisopliae(Metsch.) Sorokin for the Control ofMicrocerotermes diversusSilv.
Authors: Cheraghi Amir , Habibpour Behzad , Mossadegh Mohammad Saied
Published: January 2013

Microcerotermes diversusSilvestri (Isoptera, Termitidae) is considered to be the most destructive termite in Khuzestan province (Iran), and its control by conventional methods is often difficult. Biological control using entomopathogenic fungi could be an alternative management strategy. Performance of a bait matrix treated with the entomopathogenic fungusMetarhizium anisopliae(Metsch.) Sorokin, Strain Saravan (DEMI 001), againstM. diversuswas evaluated in this paper. The highest rate of mortality occurred at concentrations of 3.7 × 107and 3.5 × 108(conidia per mL). There was no significant difference between treatments, in the rate of feeding on the bait. The fungal pathogen was not repellent to the target termite over the conidial concentrations used. The current results suggest potential of such bait system in controlling termite. However the effectiveness ofM. anisopliaeas a component of integrated pest management forM. diversusstill needs to be proven under field conditions.
Human Carboxylesterase-2 Hydrolyzes the Prodrug of Gemcitabine (LY2334737) and Confers Prodrug Sensitivity to Cancer Cells
Authors: Pratt Susan E. , Durland-Busbice Sara , Shepard Robert L. , Heinz-Taheny Kathleen , Iversen Philip W. , Dantzig Anne H.
Published: January 2013

Purpose: The oral prodrug of gemcitabine LY2334737 is cleaved systemically to gemcitabine; the mechanism responsible for hydrolysis is unknown. LY2334737 cytotoxicity was tested in the NCI-60 panel; mining of microarray expression data identified carboxylesterase (CES) as a top hydrolase candidate. Studies examined whether CES is responsible for hydrolysis and whether cellular CES expression confers prodrug sensitivity.

Experimental Design: Human recombinant CES isozymes were assayed for LY2334737 hydrolysis. Stable CES-overexpressing HCT-116 transfectants and a SK-OV-3 knockdown were prepared. Cell lines were tested for drug sensitivity and CES expression by quantitative real time-PCR (qRT-PCR), Western blotting, and immunohistochemical staining. Bystander cytotoxicity studies were conducted with GFP-tagged PC-3 cells as the reporter cell line. Therapeutic response of the HCT-116 transfectants was evaluated in xenografts.

Results: Of 3 human CES isozymes tested, only CES2 hydrolyzed LY2334737. Five cell lines that express CES2 responded to LY2334737 treatment. LY2334737 was less cytotoxic to a SK-OV-3 CES2 knockdown than parental cells. The drug response of CES2-transfected HCT-116 cells correlated with CES2 expression level. Bystander studies showed statistically greater PC-3–GFP growth inhibition by LY2334737 when cells were cocultured with CES2 and not mock transfectants. Oral treatment of xenograft models with 3.2 mg/kg LY2334737 once a day for 21 days showed greater tumor growth inhibition of CES2 transfectant than the mock transfectant (P ≤ 0.001).

Conclusions: CES2 is responsible for the slow hydrolysis of LY2334737. Because intact prodrug circulates at high plasma levels after oral LY2334737 administration, improved response rates may be observed by tailoring LY2334737 treatment to patients with CES2 tumor expression. Clin Cancer Res; 19(5); 1159–68. ©2012 AACR.