bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of TRPV1 channels by a naturally occurring omega-9 fatty acid reduces pain and itch
Authors: Morales-Lázaro Sara L. , Llorente Itzel , Sierra-Ramírez Félix , López-Romero Ana E. , Ortíz-Rentería Miguel , Serrano-Flores Barbara , Simon Sidney A. , Islas León D. , Rosenbaum Tamara 
Published: October 2016

AbstractThe transient receptor potential vanilloid 1 (TRPV1) ion channel is mainly found in primary nociceptive afferents whose activity has been linked to pathophysiological conditions including pain, itch and inflammation. Consequently, it is important to identify naturally occurring antagonists of this channel. Here we show that a naturally occurring monounsaturated fatty acid, oleic acid, inhibits TRPV1 activity, and also pain and itch responses in mice by interacting with the vanilloid (capsaicin)-binding pocket and promoting the stabilization of a closed state conformation. Moreover, we report an itch-inducing molecule, cyclic phosphatidic acid, that activates TRPV1 and whose pruritic activity, as well as that of histamine, occurs through the activation of this ion channel. These findings provide insights into the molecular basis of oleic acid inhibition of TRPV1 and also into a way of reducing the pathophysiological effects resulting from its activation.
Actomyosin-dependent dynamic spatial patterns of cytoskeletal components drive mesoscale podosome organization
Authors: Meddens Marjolein B. M. , Pandzic Elvis , Slotman Johan A. , Guillet Dominique , Joosten Ben , Mennens Svenja , Paardekooper Laurent M. , Houtsmuller Adriaan B. , van den Dries Koen , Wiseman Paul W. , Cambi Alessandra 
Published: October 2016

AbstractPodosomes are cytoskeletal structures crucial for cell protrusion and matrix remodelling in osteoclasts, activated endothelial cells, macrophages and dendritic cells. In these cells, hundreds of podosomes are spatially organized in diversely shaped clusters. Although we and others established individual podosomes as micron-sized mechanosensing protrusive units, the exact scope and spatiotemporal organization of podosome clustering remain elusive. By integrating a newly developed extension of Spatiotemporal Image Correlation Spectroscopy with novel image analysis, we demonstrate that F-actin, vinculin and talin exhibit directional and correlated flow patterns throughout podosome clusters. Pattern formation and magnitude depend on the cluster actomyosin machinery. Indeed, nanoscopy reveals myosin IIA-decorated actin filaments interconnecting multiple proximal podosomes. Extending well-beyond podosome nearest neighbours, the actomyosin-dependent dynamic spatial patterns reveal a previously unappreciated mesoscale connectivity throughout the podosome clusters. This directional transport and continuous redistribution of podosome components provides a mechanistic explanation of how podosome clusters function as coordinated mechanosensory area.
Timely antiretroviral prophylaxis during pregnancy effectively reduces HIV mother-to-child transmission in eight counties in China: a prospective study during 2004–2011
Authors: Wang Qian , Wang Linhong , Fang Liwen , Wang Ailing , Jin Xi , Wang Fang , Wang Xiaoyan , Qiao Yaping , Sullivan Sheena G. , Rutherford Shannon , Zhang Lei 
Published: October 2016

AbstractThis study investigates the improvement of the prevention of mother-to-child transmission (PMTCT) of Human Immunodeficiency Virus (HIV) in China during 2004–2011. A clinic-based prospective study was conducted among HIV-positive pregnant women and their children in eight counties across China. Associated factors of mother-to-child transmission were analyzed using regression analysis. A total of 1,387 HIV+ pregnant women and 1,377 HIV-exposed infants were enrolled. The proportion of pregnant women who received HIV testing increased significantly from 45.1% to 98.9% during 2004–2011. Among whom, the proportion that received antiretroviral (ARV) prophylaxis increased from 61% to 96%, and the corresponding coverage in children increased from 85% to 97% during the same period. In contrast, single-dose nevirapine treatment during delivery declined substantially from 97.9% to 12.7%. Vertical transmission of HIV declined from 11.1% (95% confidence interval [CI]: 5.7–23.3%) in 2004 to 1.2% (95% CI: 0.1–5.8%) in 2011. Women who had a vaginal delivery (compared to emergency caesarian section (odds ratio [OR] = 0.46; 0.23–0.96)) and mothers on multi-ARVs (OR = 0.11; 0.04–0.29) were less likely to transmit HIV to their newborns. Increasing HIV screening enabled timely HIV care and prophylaxis to reduce vertical transmission of HIV. Early and consistent treatment with multi-ARVs during pregnancy is vital for PMTCT.
p21Cip1 plays a critical role in the physiological adaptation to fasting through activation of PPARα
Authors: Lopez-Guadamillas Elena , Fernandez-Marcos Pablo J. , Pantoja Cristina , Muñoz-Martin Maribel , Martínez Dolores , Gómez-López Gonzalo , Campos-Olivas Ramón , Valverde Angela M. , Serrano Manuel 
Published: October 2016

AbstractFasting is a physiological stress that elicits well-known metabolic adaptations, however, little is known about the role of stress-responsive tumor suppressors in fasting. Here, we have examined the expression of several tumor suppressors upon fasting in mice. Interestingly, p21 mRNA is uniquely induced in all the tissues tested, particularly in liver and muscle (>10 fold) and this upregulation is independent of p53. Remarkably, in contrast to wild-type mice, p21-null mice become severely morbid after prolonged fasting. The defective adaptation to fasting of p21-null mice is associated to elevated energy expenditure, accelerated depletion of fat stores and premature activation of protein catabolism in the muscle. Analysis of the liver transcriptome and cell-based assays revealed that the absence of p21 partially impairs the transcriptional program of PPARα, a key regulator of fasting metabolism. Finally, treatment of p21-null mice with a PPARα agonist substantially protects them from their accelerated loss of fat upon fasting. We conclude that p21 plays a relevant role in fasting adaptation through the positive regulation of PPARα.
The chemokine CXCL16 modulates neurotransmitter release in hippocampal CA1 area
Authors: Di Castro Maria Amalia , Trettel Flavia , Milior Giampaolo , Maggi Laura , Ragozzino Davide , Limatola Cristina 
Published: October 2016

AbstractChemokines have several physio-pathological roles in the brain. Among them, the modulation of synaptic contacts and neurotransmission recently emerged as crucial activities during brain development, in adulthood, upon neuroinflammation and neurodegenerative diseases. CXCL16 is a chemokine normally expressed in the brain, where it exerts neuroprotective activity against glutamate-induced damages through cross communication with astrocytes and the involvement of the adenosine receptor type 3 (A3R) and the chemokine CCL2. Here we demonstrated for the first time that CXCL16 exerts a modulatory activity on inhibitory and excitatory synaptic transmission in CA1 area. We found that CXCL16 increases the frequency of the miniature inhibitory synaptic currents (mIPSCs) and the paired-pulse ratio (PPR) of evoked IPSCs (eIPSCs), suggesting a presynaptic modulation of the probability of GABA release. In addition, CXCL16 increases the frequency of the miniature excitatory synaptic currents (mEPSCs) and reduces the PPR of evoked excitatory transmission, indicating that the chemokine also modulates and enhances the release of glutamate. These effects were not present in the A3RKO mice and in WT slices treated with minocycline, confirming the involvement of A3 receptors and introducing microglial cells as key mediators of the modulatory activity of CXCL16 on neurons.
Detection of Cronobacter sakazakii in powdered infant formula using an immunoliposome-based immunomagnetic concentration and separation assay
Authors: Shukla Shruti , Lee Gibaek , Song Xinjie , Park Jung Hyun , Cho Hyunjeong , Lee Eun Ju , Kim Myunghee 
Published: October 2016

AbstractThis study aimed to optimize the applicability of an immunoliposome-based immunomagnetic concentration and separation assay to facilitate rapid detection of Cronobacter sakazakii in powdered infant formula (PIF). To determine the detection limit, specificity, and pre-enrichment incubation time (0, 4, 6, and 8 h), assay tests were performed with different cell numbers of C. sakazakii (2 × 100 and 2 × 101 CFU/ml) inoculated in 10 g of PIF. The assay was able to detect as few as 2 cells of C. sakazakii/10 g of PIF sample after 6 h of pre-enrichment incubation with an assay time of 2 h 30 min. The assay was assessed for cross-reactivity with other bacterial strains and exhibited strong specificity to C. sakazakii. Moreover, the assay method was applied to the detection of C. sakazakii in PIF without pre-enrichment steps, and the results were compared with INC-ELISA and RT-PCR. The developed method was able to detect C. sakazakii in spiked PIF without pre-enrichment, whereas INC-ELISA failed to detect C. sakazakii. In addition, when compared with the results obtained with RT-PCR, our developed assay required lesser detection time. The developed assay was also not susceptible to any effect of the food matrix or background contaminant microflora.
Hexokinase I N-terminal based peptide prevents the VDAC1-SOD1 G93A interaction and re-establishes ALS cell viability
Authors: Magrì Andrea , Belfiore Ramona , Reina Simona , Tomasello Marianna Flora , Di Rosa Maria Carmela , Guarino Francesca , Leggio Loredana , De Pinto Vito , Messina Angela 
Published: October 2016

AbstractSuperoxide Dismutase 1 mutants associate with 20–25% of familial Amyotrophic Lateral Sclerosis (ALS) cases, producing toxic aggregates on mitochondria, notably in spinal cord. The Voltage Dependent Anion Channel isoform 1 (VDAC1) in the outer mitochondrial membrane is a docking site for SOD1 G93A mutant in ALS mice and the physiological receptor of Hexokinase I (HK1), which is poorly expressed in mouse spinal cord. Our results demonstrate that HK1 competes with SOD1 G93A for binding VDAC1, suggesting that in ALS spinal cord the available HK1-binding sites could be used by SOD1 mutants for docking mitochondria, producing thus organelle dysfunction. We tested this model by studying the action of a HK1-N-terminal based peptide (NHK1). This NHK1 peptide specifically interacts with VDAC1, inhibits the SOD1 G93A binding to mitochondria and restores the viability of ALS model NSC34 cells. Altogether, our results suggest that NHK1 peptide could be developed as a therapeutic tool in ALS, predicting an effective role also in other proteinopathies.
Navigable rivers facilitated the spread and recurrence of plague in pre-industrial Europe
Authors: Yue Ricci P. H. , Lee Harry F. , Wu Connor Y. H. 
Published: October 2016

AbstractInfectious diseases have become a rising challenge to mankind in a globalizing world. Yet, little is known about the inland transmission of infectious diseases in history. In this study, we based on the spatio-temporal information of 5559 plague (Yersinia pestis) outbreaks in Europe and its neighboring regions in AD1347–1760 to statistically examine the connection between navigable rivers and plague outbreak. Our results showed that 95.5% of plague happened within 10 km proximity of navigable rivers. Besides, the count of plague outbreak was positively correlated with the width of river and negatively correlated with the distance between city and river. This association remained robust in different regression model specifications. An increase of 100 m in the width of river and a shortening of 1 km distance between city and river resulted in 9 and 0.96 more plague outbreaks in our study period, respectively. Such relationship shows a declining trend over our study period due to the expansion of city and technological advancement in overland transportation. This study elucidates the key role of navigable river in the dissemination of plague in historical Europe.
Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies
Authors: Soler Miguel A. , de Marco Ario , Fortuna Sara 
Published: October 2016

AbstractNanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features. One set contained point mutations introduced to humanize a wild type sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae and human hallmarks. The method resulted in accurate scoring approaches to predict experimental yields and enabled to identify the structural modifications induced by mutations. This work is a promising tool for the in silico development of single-domain antibodies and opens the opportunity to customize single functional domains of larger macromolecules.
Plasmonic/Magnetic Multifunctional nanoplatform for Cancer Theranostics
Authors: Ravichandran M. , Oza Goldie , Velumani S. , Ramirez Jose Tapia , Garcia-Sierra Francisco , Andrade Norma Barragan , Vera A. , Leija L. , Garza-Navarro Marco A. 
Published: October 2016

AbstractA multifunctional magneto-plasmonic CoFe2O4@Au core-shell nanoparticle was developed by iterative-seeding based method. This nanocargo consists of a cobalt ferrite kernel as a core (Nk) and multiple layers of gold as a functionalizable active stratum, (named as Nk@A after fifth iteration). Nk@A helps in augmenting the physiological stability and enhancing surface plasmon resonance (SPR) property. The targeted delivery of Doxorubicin using Nk@A as a nanopayload is demonstrated in this report. The drug release profile followed first order rate kinetics optimally at pH 5.4, which is considered as an endosomal pH of cells. The cellular MR imaging showed that Nk@A is an efficient T2 contrast agent for both L6 (r2-118.08 mM−1s−1) and Hep2 (r2-217.24 mM−1s−1) cells. Microwave based magnetic hyperthermia studies exhibited an augmentation in the temperature due to the transformation of radiation energy into heat at 2.45 GHz. There was an enhancement in cancer cell cytotoxicity when hyperthermia combined with chemotherapy. Hence, this single nanoplatform can deliver 3-pronged theranostic applications viz., targeted drug-delivery, T2 MR imaging and hyperthermia.
Instability Analysis and Free Volume Simulations of Shear Band Directions and Arrangements in Notched Metallic Glasses
Authors: Li Weidong , Gao Yanfei , Bei Hongbin 
Published: October 2016

AbstractAs a commonly used method to enhance the ductility in bulk metallic glasses (BMGs), the introduction of geometric constraints blocks and confines the propagation of the shear bands, reduces the degree of plastic strain on each shear band so that the catastrophic failure is prevented or delayed, and promotes the formation of multiple shear bands. The clustering of multiple shear bands near notches is often interpreted as the reason for improved ductility. Experimental works on the shear band arrangements in notched metallic glasses have been extensively carried out, but a systematic theoretical study is lacking. Using instability theory that predicts the onset of strain localization and the free-volume-based finite element simulations that predict the evolution of shear bands, this work reveals various categories of shear band arrangements in double edge notched BMGs with respect to the mode mixity of the applied stress fields. A mechanistic explanation is thus provided to a number of related experiments and especially the correlation between various types of shear bands and the stress state.
Dirac semimetal thin films in in-plane magnetic fields
Authors: Siu Zhuo Bin , Jalil Mansoor B. A. , Tan Seng Ghee 
Published: October 2016

AbstractIn this work we study the effects of in-plane magnetic fields on thin films of the Dirac Semimetal (DSM) Na3Bi where one of the in-plane directions is perpendicular to the k-separation between the two Weyl nodes that exist for each spin orientation. We show numerically that the states localized near the surfaces of these thin films are related to the Fermi arc states in semi-infinite slabs. Due to the anisotropy between the two in-plane directions, the application of a magnetic field along these directions have differing effects. A field parallel to the k space separation between the Weyl nodes leads to a broadening of the surface state band and the formation of an energy plateau, while a perpendicular field shifts the energy where the hole and particle bands meet upwards, and sharpens the tips of the bands. We illustrate the effects of these changes to the dispersion relation by studying the transmission from a source segment without a magnetic field to a drain segment with a field, with the field and interface at various in-plane directions.
Correlated activity of cortical neurons survives extensive removal of feedforward sensory input
Authors: Shapcott Katharine A. , Schmiedt Joscha T. , Saunders Richard C. , Maier Alexander , Leopold David A. , Schmid Michael C. 
Published: October 2016

AbstractA fundamental property of brain function is that the spiking activity of cortical neurons is variable and that some of this variability is correlated between neurons. Correlated activity not due to the stimulus arises from shared input but the neuronal circuit mechanisms that result in these noise correlations are not fully understood. Here we tested in the visual system if correlated variability in mid-level area V4 of visual cortex is altered following extensive lesions of primary visual cortex (V1). To this end we recorded longitudinally the neuronal correlations in area V4 of two behaving macaque monkeys before and after a V1 lesion while the monkeys fixated a grey screen. We found that the correlations of neuronal activity survived the lesions in both monkeys. In one monkey, the correlation of multi-unit spiking signals was strongly increased in the first week post-lesion, while in the second monkey, correlated activity was slightly increased, but not greater than some week-by-week fluctuations observed. The typical drop-off of inter-neuronal correlations with cortical distance was preserved after the lesion. Therefore, as V4 noise correlations remain without feedforward input from V1, these results suggest instead that local and/or feedback input seem to be necessary for correlated activity.
Genomics-assisted characterization of a breeding collection of Apios americana, an edible tuberous legume
Authors: Belamkar Vikas , Farmer Andrew D. , Weeks Nathan T. , Kalberer Scott R. , Blackmon William J. , Cannon Steven B. 
Published: October 2016

AbstractFor species with potential as new crops, rapid improvement may be facilitated by new genomic methods. Apios (Apios americana Medik.), once a staple food source of Native American Indians, produces protein-rich tubers, tolerates a wide range of soils, and symbiotically fixes nitrogen. We report the first high-quality de novo transcriptome assembly, an expression atlas, and a set of 58,154 SNP and 39,609 gene expression markers (GEMs) for characterization of a breeding collection. Both SNPs and GEMs identify six genotypic clusters in the collection. Transcripts mapped to the Phaseolus vulgaris genome–another phaseoloid legume with the same chromosome number–provide provisional genetic locations for 46,852 SNPs. Linkage disequilibrium decays within 10 kb (based on the provisional genetic locations), consistent with outcrossing reproduction. SNPs and GEMs identify more than 21 marker-trait associations for at least 11 traits. This study demonstrates a holistic approach for mining plant collections to accelerate crop improvement.
Effects of contrast-enhancement, reconstruction slice thickness and convolution kernel on the diagnostic performance of radiomics signature in solitary pulmonary nodule
Authors: He Lan , Huang Yanqi , Ma Zelan , Liang Cuishan , Liang Changhong , Liu Zaiyi 
Published: October 2016

AbstractThe Effects of contrast-enhancement, reconstruction slice thickness and convolution kernel on the diagnostic performance of radiomics signature in solitary pulmonary nodule (SPN) remains unclear. 240 patients with SPNs (malignant, n = 180; benign, n = 60) underwent non-contrast CT (NECT) and contrast-enhanced CT (CECT) which were reconstructed with different slice thickness and convolution kernel. 150 radiomics features were extracted separately from each set of CT and diagnostic performance of each feature were assessed. After feature selection and radiomics signature construction, diagnostic performance of radiomics signature for discriminating benign and malignant SPN was also assessed with respect to the discrimination and classification and compared with net reclassification improvement (NRI). Our results showed NECT-based radiomics signature demonstrated better discrimination and classification capability than CECT in both primary (AUC: 0.862 vs. 0.829, p = 0.032; NRI = 0.578) and validation cohort (AUC: 0.750 vs. 0.735, p = 0.014; NRI = 0.023). Thin-slice (1.25 mm) CT-based radiomics signature had better diagnostic performance than thick-slice CT (5 mm) in both primary (AUC: 0.862 vs. 0.785, p = 0.015; NRI = 0.867) and validation cohort (AUC: 0.750 vs. 0.725, p = 0.025; NRI = 0.467). Standard convolution kernel-based radiomics signature had better diagnostic performance than lung convolution kernel-based CT in both primary (AUC: 0.785 vs. 0.770, p = 0.015; NRI = 0.156) and validation cohort (AUC: 0.725 vs.0.686, p = 0.039; NRI = 0.467). Therefore, this study indicates that the contrast-enhancement, reconstruction slice thickness and convolution kernel can affect the diagnostic performance of radiomics signature in SPN, of which non-contrast, thin-slice and standard convolution kernel-based CT is more informative.
Simultaneous effects on parvalbumin-positive interneuron and dopaminergic system development in a transgenic rat model for sporadic schizophrenia
Authors: Hamburg Hannah , Trossbach Svenja V. , Bader Verian , Chwiesko Caroline , Kipar Anja , Sauvage Magdalena , Crum William R. , Vernon Anthony C. , Bidmon Hans J. , Korth Carsten 
Published: October 2016

AbstractTo date, unequivocal neuroanatomical features have been demonstrated neither for sporadic nor for familial schizophrenia. Here, we investigated the neuroanatomical changes in a transgenic rat model for a subset of sporadic chronic mental illness (CMI), which modestly overexpresses human full-length, non-mutant Disrupted-in-Schizophrenia 1 (DISC1), and for which aberrant dopamine homeostasis consistent with some schizophrenia phenotypes has previously been reported. Neuroanatomical analysis revealed a reduced density of dopaminergic neurons in the substantia nigra and reduced dopaminergic fibres in the striatum. Parvalbumin-positive interneuron occurrence in the somatosensory cortex was shifted from layers II/III to V/VI, and the number of calbindin-positive interneurons was slightly decreased. Reduced corpus callosum thickness confirmed trend-level observations from in vivo MRI and voxel-wise tensor based morphometry. These neuroanatomical changes help explain functional phenotypes of this animal model, some of which resemble changes observed in human schizophrenia post mortem brain tissues. Our findings also demonstrate how a single molecular factor, DISC1 overexpression or misassembly, can account for a variety of seemingly unrelated morphological phenotypes and thus provides a possible unifying explanation for similar findings observed in sporadic schizophrenia patients. Our anatomical investigation of a defined model for sporadic mental illness enables a clearer definition of neuroanatomical changes associated with subsets of human sporadic schizophrenia.