bluuebunny/crossref_metadata_2025_split huggingface dataset:
Omega‐3 polyunsaturated fatty acids and proanthocyanidins improve postprandial metabolic flexibility in rat
Authors: Casanova Ester , Baselga‐Escudero Laura , Ribas‐Latre Aleix , Arola‐Arnal Anna , Bladé Cinta , Arola Lluís , Salvadó M. Josepa 
Published: August 2013

AbstractPostprandial lipemia influences the development of atherosclerosis, which itself constitutes a risk factor for the development of cardiovascular diseases. The introduction of bioactive compounds may prevent these deleterious effects. Proanthocyanidins are potent antioxidants that have hypolipidemic properties, while omega‐3 polyunsaturated fatty acids (ω3 PUFAs) stimulate fatty acid oxidation and gene expression programs, controlling mitochondrial functions. In this study, we investigated the effects of acute treatment of ω3 PUFAs and proanthocyanidins on the metabolic flexibility and lipid handling profiles in the skeletal muscle and adipose tissue of rats that were raised on diets, high in saturated fatty acids. For this, oil rich in docosahexaenoic (DHA‐OR), grape seed proanthocyanidins extract (GSPE), or both substances (GSPE + DHA‐OR) were administered with an overload of lard oil to healthy Wistar rats. Our results indicate that the addition of DHA‐OR to lard oil increases insulin sensitivity and redirects fatty acids toward skeletal muscle, thereby activating fatty acid oxidation. We also observed an improvement in adipose mitochondrial functionality and uncoupling. In contrast, GSPE lowers lipidemia, prevents muscle reactive oxygen species (ROS) production and damage, furthermore, activates mitochondrial biogenesis and lipogenesis in adipose tissue. The addition of GSPE+DHA‐OR to lard resulted in nearly all the effects of DHA‐OR and GSPE administered individually, but the combined administration resulted in a more attenuated profile. © 2013 BioFactors, 40(1):146–156, 2014
Berberine acts as a natural inhibitor of Wnt/β‐catenin signaling—Identification of more active 13‐arylalkyl derivatives
Authors: Albring Kai Frederik , Weidemüller Julia , Mittag Sonnhild , Weiske Jörg , Friedrich Karlheinz , Geroni M. Cristina , Lombardi Paolo , Huber Otmar 
Published: August 2013

AbstractAberrant activation of the canonical Wnt/β‐catenin signaling pathway has been reported for numerous tumors of different origins. In most cases, mutations in components of the Wnt signaling pathway or in β‐catenin itself were detected which ultimately induce a genetic program that promotes cell proliferation and attenuates apoptosis. Thus, targeting of Wnt/β‐catenin signaling is of specific therapeutic interest. Herein, we investigated the plant‐derived isoquinoline alkaloid berberine, which has been reported to have anticancer activity, and synthetic 13‐arylalkyl derivatives thereof for their effects on Wnt/β‐catenin signaling. Berberine did not show major effects on viability of HEK‐293 embryonic kidney and HCT116 colon carcinoma cells and was not toxic in concentrations up to 20 µM. Berberine inhibited β‐catenin transcriptional activity and attenuated anchorage‐independent growth. As a result of berberine treatment, cellular levels of active β‐catenin were reduced concomitant with an increase in the expression of E‐cadherin. However, in unstimulated cells, the effects on β‐catenin levels were low. A screen of synthetic 13‐arylalkyl berberine derivatives identified compounds exhibiting activities superior to those of the naturally occurring parent substance with more than 100‐fold lower EC50 values for Wnt‐repression. Thus, berberine and its synthetic derivatives represent potential therapeutic agents to inhibit Wnt/β‐catenin signaling in tumorigenesis. © 2013 BioFactors, 39(6):652–662, 2013
Development and validation of an LCMS method to determine the pharmacokinetic profiles of caffeic acid phenethyl amide and caffeic acid phenethyl ester in male Sprague–Dawley rats
Authors: Yang John , Bowman Phillip D. , Kerwin Sean M. , Stavchansky Salomon 
Published: August 2013

ABSTRACTA validated LCMS method was developed for the quantitative determination of caffeic acid phenethyl amide (CAPA) and caffeic acid phenethyl ester (CAPE) from rat plasma. Separation was achieved using a reverse‐phase C12 HPLC column (150 × 2.00 mm, 4 µm) with gradient elution running water (A) and acetonitrile (B). Mass spectrometry was performed with electrospray ionization in negative mode. This method was used to determine the pharmacokinetic profiles of CAPA and CAPE in male Sprague–Dawley rats following intravenous bolus administration of 5, 10 and 20 mg/kg of CAPA and 20 mg/kg of CAPE. The pharmacokinetic analysis suggests the lack of dose proportionality in the dose range of 5–20 mg/kg of CAPA. Total clearance values for CAPA ranged from 45 to 156 mL/min and decreased with increasing dose of CAPA. The volume of distribution for CAPA ranged from 17,750 to 52,420 mL, decreasing with increasing dose. The elimination half‐life for CAPA ranged from 243.1 to 295.8 min and no statistically significant differences were observed between dose groups in the range of 5–20 mg/kg (p > 0.05). The elimination half‐life for CAPE was found to be 92.26 min. Copyright © 2013 John Wiley & Sons, Ltd.
Simple and validated UHPLC method coupled to UV detection for determination of daptomycin in human plasma and urine
Authors: Naito Takafumi , Yamada Takahiro , Yagi Tatsuya , Kawakami Junichi 
Published: August 2013

ABSTRACTDaptomycin, a lipopeptide antibiotic with excellent activity against Gram‐positive bacteria, is excreted primarily by the kidneys. Development of effective chromatographic methodologies for the determination of daptomycin in human specimens is necessary for clinical use. This study developed a simple and validated ultra‐high‐performance liquid chromatography method coupled to ultraviolet detection for determination of daptomycin in human plasma and urine. After the pretreatments involving protein precipitation, the supernatants were separated using a 2.3 µm particle size octadecylsilyl column, and the run time was 1 min. The calibration curves were linear over the concentration ranges of 2–200 mg/L for plasma and 25–300 mg/L for urine. Intra‐ and inter‐assay precision and accuracy values of plasma were within 13.5 and 92–100% and within 10.7 and 100–107%, respectively. Those of urine were within 5.0 and 101–104% and within 3.7 and 100–101%, respectively. The validated method was applied to the determination of plasma and urine samples in patients receiving 4–6 mg/kg of intravenous daptomycin, resulting in sufficient sensitivity for evaluating the plasma exposure and urinary excretion. In conclusion, the present method with acceptable analytical performance can be helpful for evaluating the pharmacokinetic disposition of daptomycin in clinical settings. Copyright © 2013 John Wiley & Sons, Ltd.
Structural organization and function of mouse photoreceptor ribbon synapses involve the immunoglobulin protein synaptic cell adhesion molecule 1
Authors: Ribic Adema , Liu Xinran , Crair Michael C. , Biederer Thomas 
Published: August 2013

ABSTRACTAdhesive interactions in the retina instruct the developmental specification of inner retinal layers. However, potential roles of adhesion in the development and function of photoreceptor synapses remain incompletely understood. This contrasts with our understanding of synapse development in the CNS, which can be guided by select adhesion molecules such as the Synaptic Cell Adhesion Molecule 1 (SynCAM 1/CADM1/nectin‐like 2 protein). This immunoglobulin superfamily protein modulates the development and plasticity of classical excitatory synapses. We show here by immunoelectron microscopy and immunoblotting that SynCAM 1 is expressed on mouse rod photoreceptors and their terminals in the outer nuclear and plexiform layers in a developmentally regulated manner. Expression of SynCAM 1 on rods is low in early postnatal stages (P3–P7) but increases after eye opening (P14). In support of functional roles in the photoreceptors, electroretinogram recordings demonstrate impaired responses to light stimulation in SynCAM 1 knockout (KO) mice. In addition, the structural integrity of synapses in the OPL requires SynCAM 1. Quantitative ultrastructural analysis of SynCAM 1 KO retina measured fewer fully assembled, triadic rod ribbon synapses. Furthermore, rod synapse ribbons are shortened in KO mice, and protein levels of Ribeye, a major structural component of ribbons, are reduced in SynCAM 1 KO retina. Together, our results implicate SynCAM 1 in the synaptic organization of the rod visual pathway and provide evidence for novel roles of synaptic adhesion in the structural and functional integrity of ribbon synapses. J. Comp. Neurol. 522:900–920, 2014. © 2013 Wiley Periodicals, Inc.
Electron tomography on γ‐aminobutyric acid‐ergic synapses reveals a discontinuous postsynaptic network of filaments
Authors: Linsalata Alexander E. , Chen Xiaobing , Winters Christine A. , Reese Thomas S. 
Published: August 2013

ABSTRACTThe regulation of synaptic strength at γ‐aminobutyric acid (GABA)‐ergic synapses is dependent on the dynamic capture, retention, and modulation of GABA A‐type receptors by cytoplasmic proteins at GABAergic postsynaptic sites. How these proteins are oriented and organized in the postsynaptic cytoplasm is not yet established. To better understand these structures and gain further insight into the mechanisms by which they regulate receptor populations at postsynaptic sites, we utilized electron tomography to examine GABAergic synapses in dissociated rat hippocampal cultures. GABAergic synapses were identified and selected for tomography by using a set of criteria derived from the structure of immunogold‐labeled GABAergic synapses. Tomography revealed a complex postsynaptic network composed of filaments that extend ∼100 nm into the cytoplasm from the postsynaptic membrane. The distribution of these postsynaptic filaments was strikingly similar to that of the immunogold label for gephyrin. Filaments were interconnected through uniform patterns of contact, forming complexes composed of 2–12 filaments each. Complexes did not link to form an integrated, continuous scaffold, suggesting that GABAergic postsynaptic specializations are less rigidly organized than glutamatergic postsynaptic densities. J. Comp. Neurol. 522:921–936, 2014. © 2013 Wiley Periodicals, Inc.
Tonotopic organization of vertical cells in the dorsal cochlear nucleus of the CBA/J mouse
Authors: Muniak Michael A. , Ryugo David K. 
Published: August 2013

ABSTRACTThe systematic and topographic representation of frequency is a first principle of organization throughout the auditory system. The dorsal cochlear nucleus (DCN) receives direct tonotopic projections from the auditory nerve (AN) as well as secondary and descending projections from other sources. Among the recipients of AN input in the DCN are vertical cells (also called tuberculoventral cells), glycinergic interneurons thought to provide on‐ or near‐best‐frequency feed‐forward inhibition to principal cells in the DCN and various cells in the anteroventral cochlear nucleus (AVCN). Differing lines of physiological and anatomical evidence suggest that vertical cells and their projections are organized with respect to frequency, but this has not been conclusively demonstrated in the intact mammalian brain. To address this issue, we retrogradely labeled vertical cells via physiologically targeted injections in the AVCN of the CBA/J mouse. Results from multiple cases were merged with a normalized 3D template of the cochlear nucleus (Muniak et al. [] J. Comp. Neurol. 521:1510–1532) to demonstrate quantitatively that the arrangement of vertical cells is tonotopic and aligned to the innervation pattern of the AN. These results suggest that vertical cells are well positioned for providing immediate, frequency‐specific inhibition onto cells of the DCN and AVCN to facilitate spectral processing. J. Comp. Neurol. 522:937–949, 2014. © 2013 Wiley Periodicals, Inc.
Expression of m1‐type muscarinic acetylcholine receptors by parvalbumin‐immunoreactive neurons in the primary visual cortex: A comparative study of rat, guinea pig, ferret, macaque, and human
Authors: Disney Anita A. , Reynolds John H. 
Published: August 2013

ABSTRACTCholinergic neuromodulation is a candidate mechanism for aspects of arousal and attention in mammals. We have reported previously that cholinergic modulation in the primary visual cortex (V1) of the macaque monkey is strongly targeted toward GABAergic interneurons, and in particular that the vast majority of parvalbumin‐immunoreactive (PV) neurons in macaque V1 express the m1‐type (pirenzepine‐sensitive, Gq‐coupled) muscarinic ACh receptor (m1AChR). In contrast, previous physiological data indicates that PV neurons in rats rarely express pirenzepine‐sensitive muscarinic AChRs. To examine further this apparent species difference in the cholinergic effectors for the primary visual cortex, we have conducted a comparative study of the expression of m1AChRs by PV neurons in V1 of rats, guinea pigs, ferrets, macaques, and humans. We visualize PV‐ and mAChR‐immunoreactive somata by dual‐immunofluorescence confocal microscopy and find that the species differences are profound; the vast majority (>75%) of PV‐ir neurons in macaques, humans, and guinea pigs express m1AChRs. In contrast, in rats only ∼25% of the PV population is immunoreactive for m1AChRs. Our data reveal that while they do so much less frequently than in primates, PV neurons in rats do express Gq‐coupled muscarinic AChRs, which appear to have gone undetected in the previous in vitro studies. Data such as these are critical in determining the species that represent adequate models for the capacity of the cholinergic system to modulate inhibition in the primate cortex. J. Comp. Neurol. 522:986–1003, 2014. © 2013 Wiley Periodicals, Inc.
Organization of sensory input to the nociceptive‐specific cutaneous trunk muscle reflex in rat, an effective experimental system for examining nociception and plasticity
Authors: Petruska Jeffrey C. , Barker Darrell F. , Garraway Sandra M. , Trainer Robert , Fransen James W. , Seidman Peggy A. , Soto Roy G. , Mendell Lorne M. , Johnson Richard D. 
Published: August 2013

ABSTRACTDetailed characterization of neural circuitries furthers our understanding of how nervous systems perform specific functions and allows the use of those systems to test hypotheses. We have characterized the sensory input to the cutaneous trunk muscle (CTM; also cutaneus trunci [rat] or cutaneus maximus [mouse]) reflex (CTMR), which manifests as a puckering of the dorsal thoracolumbar skin and is selectively driven by noxious stimuli. CTM electromyography and neurogram recordings in naïve rats revealed that CTMR responses were elicited by natural stimuli and electrical stimulation of all segments from C4 to L6, a much greater extent of segmental drive to the CTMR than previously described. Stimulation of some subcutaneous paraspinal tissue can also elicit this reflex. Using a selective neurotoxin, we also demonstrate differential drive of the CTMR by trkA‐expressing and nonexpressing small‐diameter afferents. These observations highlight aspects of the organization of the CTMR system that make it attractive for studies of nociception and anesthesiology and plasticity of primary afferents, motoneurons, and the propriospinal system. We use the CTMR system to demonstrate qualitatively and quantitatively that experimental pharmacological treatments can be compared with controls applied either to the contralateral side or to another segment, with the remaining segments providing controls for systemic or other treatment effects. These data indicate the potential for using the CTMR system as both an invasive and a noninvasive quantitative assessment tool providing improved statistical power and reduced animal use. J. Comp. Neurol. 522:1048–1071, 2014. © 2013 Wiley Periodicals, Inc.
Do we need continuous glucose monitoring in type 2 diabetes?
Authors: Maurizi Anna Rita , Pozzilli Paolo 
Published: August 2013

AbstractSelf‐monitoring of blood glucose (SMBG) is recommended as a core component of diabetic patient's management but it can provide only intermittent snapshots of blood glucose levels missing often hyperglycaemic or hypoglycaemic excursions. Similarly HbA1c alone is unable to provide detailed diagnostic information and it has several limitations. In the modern diabetes monitoring, Continuous Glucose Monitoring (CGM) could be considered as a third pillar, since it provides information on day‐to‐day change of blood glucose levels and helps achieving treatment targets without increasing the risk of hypoglycaemia. Therefore the use of CGM may reduce glucose variability, improving glycaemic control and decreasing long‐term diabetes complications. In fact the availability of continuous glucose data for patients with low and high glucose alerts may impact quality of life with short‐ and long‐term effectiveness. Moreover CGM can be used as a powerful motivational device to change type 2 diabetic patients’ lifestyle and to improve their quality of life. Although the studies on the economic feasibility to use CGM as an educational tool must be carried out, we suggest that it can be used as a powerful motivational device to change patients’ lifestyle and to improve glycaemic control in type 2 diabetes (T2D). This article is protected by copyright. All rights reserved.
Lack of metformin effect on mouse embryo AMPK activity: implications for metformin treatment during pregnancy
Authors: Lee Hyung‐yul , Wei Dan , Loeken Mary R. 
Published: August 2013

AbstractBackgroundAdenosine monophosphate‐activated protein kinase (AMPK) is stimulated in embryos during diabetic pregnancy by maternal hyperglycaemia‐induced embryo oxidative stress. Stimulation of AMPK disrupts embryo gene expression and causes neural tube defects. Metformin, which may be taken during early pregnancy, has been reported to stimulate AMPK activity. Thus, the benefits of improved glycaemic control could be offset by stimulated embryo AMPK activity. Here, we investigated whether metformin can stimulate AMPK activity in mouse embryos and can adversely affect embryo gene expression and neural tube defects.MethodsPregnant nondiabetic mice were administered metformin beginning on the first day of pregnancy. Activation of maternal and embryo AMPK [phospho‐AMPK α (Thr172) relative to total AMPK], expression of Pax3, a gene required for neural tube closure, and neural tube defects were studied. Mouse embryonic stem cells were used as a cell culture model of embryonic neuroepithelium to study metformin effects on AMPK and Pax3 expression.ResultsMetformin had no effect on AMPK in embryos or maternal skeletal muscle but increased activated AMPK in maternal liver. Metformin did not inhibit Pax3 expression or increase neural tube defects. However, metformin increased activated AMPK and inhibited Pax3 expression by mouse embryonic stem cells. Mate1/Slc47a1 and Oct3/Slc22a, which encode metformin transporters, were expressed at barely detectable levels by embryos.ConclusionsAlthough metformin can have effects associated with diabetic embryopathy in vitro, the lack of effects on mouse embryos in vivo may be due to lack of metformin transporters and indicates that the benefits of metformin on glycaemic control are not counteracted by stimulation of embryo AMPK activity and consequent embryopathy. Copyright © 2013 John Wiley & Sons, Ltd.
Population genetics structure of glyphosate‐resistant Johnsongrass (Sorghum halepense L. Pers) does not support a single origin of the resistance
Authors: Fernández Luis , de Haro Luis Alejandro , Distefano Ana J. , Carolina Martínez Maria , Lía Verónica , Papa Juan C. , Olea Ignacio , Tosto Daniela , Esteban Hopp Horacio 
Published: August 2013

AbstractSingle sequence repeats (SSR) developed for Sorghum bicolor were used to characterize the genetic distance of 46 different Sorghum halepense (Johnsongrass) accessions from Argentina some of which have evolved toward glyphosate resistance. Since Johnsongrass is an allotetraploid and only one subgenome is homologous to cultivated sorghum, some SSR loci amplified up to two alleles while others (presumably more conserved loci) amplified up to four alleles. Twelve SSR providing information of 24 loci representative of Johnsongrass genome were selected for genetic distance characterization. All of them were highly polymorphic, which was evidenced by the number of different alleles found in the samples studied, in some of them up to 20. UPGMA and Mantel analysis showed that Johnsongrass glyphosate‐resistant accessions that belong to different geographic regions do not share similar genetic backgrounds. In contrast, they show closer similarity to their neighboring susceptible counterparts. Discriminant Analysis of Principal Components using the clusters identified by K‐means support the lack of a clear pattern of association among samples and resistance status or province of origin. Consequently, these results do not support a single genetic origin of glyphosate resistance. Nucleotide sequencing of the 5‐enolpyruvylshikimate‐3‐phosphate synthase (EPSPS) encoding gene from glyphosate‐resistant and susceptible accessions collected from different geographic origins showed that none presented expected mutations in aminoacid positions 101 and 106 which are diagnostic of target‐site resistance mechanism.
Reach‐scale movements of bull trout (Salvelinus confluentus) relative to hydropeaking operations in the Columbia River, Canada
Authors: Taylor Mark K. , Hasler Caleb T. , Hinch Scott G. , Lewis Bronwen , Schmidt Dana C. , Cooke Steven J. 
Published: August 2013

ABSTRACTDespite the widespread use of on‐demand hydropeaking operations for generating electricity from rivers, relatively little is known about how pulsed flows influence the behaviour of fishes. We studied the movements of bull trout by using radio telemetry in a hydropeaking reach of the upper Columbia River, near Revelstoke, British Columbia, Canada. Fifty‐seven bull trout were located every 12 h to evaluate the effects of discharge magnitude and rate of change on the: (1) odds of movement; (2) movement distances; and (3) movement direction. Twelve‐hour mean discharge magnitude had a negative effect on the odds of bull movement: for every 100 m3 s−1 increase in discharge, movement odds decreased by a factor of 0·91. Movement odds were unrelated to 12‐h discharge rate of change. Every 1 °C increase in water temperature increased movement odds by a factor of 1·27. Also, bull trout were more likely to move during the AM versus PM by a factor of 1·36. Movement distances were related to diel period, sex and fork length; however, these effects were not very strong. We found no evidence of downstream displacement during periods of high or changing river discharge. In fact, movement direction was unpredictable, which is consistent with the salmonid non‐migratory movement literature. Collectively, these findings provide insight into the biology of bull trout during an understudied seasonal life‐history period (i.e. autumn). It also informs river managers that bull trout movement can be modulated by operational water release from a dam. Copyright © 2013 John Wiley & Sons, Ltd.