bluuebunny/crossref_metadata_2025_split huggingface dataset:
Invasive lobular and ductal breast carcinoma differ in immune response, protein translation efficiency and metabolism
Authors: Du Tian , Zhu Li , Levine Kevin M. , Tasdemir Nilgun , Lee Adrian V. , Vignali Dario A. A. , Houten Bennett Van , Tseng George C. , Oesterreich Steffi 
Published: May 2018

AbstractInvasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer following invasive ductal carcinoma (IDC). ILC differs from IDC in a number of histological and clinical features, such as single strand growth, difficulty in detection, and frequent late recurrences. To understand the molecular pathways involved in the clinical characteristics of ILC, we compared the gene expression profiles of luminal A ILC and luminal A IDC using data from TCGA and utilized samples from METABRIC as a validation data set. Top pathways that were significantly enriched in ILC were related to immune response. ILC exhibited a higher activity of almost all types of immune cells based on cell type-specific signatures compared to IDC. Conversely, pathways that were less enriched in ILC were related to protein translation and metabolism, which we functionally validated in cell lines. The higher immune activity uncovered in our study highlights the currently unexplored potential of a response to immunotherapy in a subset of patients with ILC. Furthermore, the lower rates of protein translation and metabolism - known features of tumor dormancy - may play a role in the late recurrences of ILC and lower detection rate in mammography and PET scanning.
Antimicrobial photodynamic therapy mediated by methylene blue and potassium iodide to treat urinary tract infection in a female rat model
Authors: Huang Ying-Ying , Wintner Anton , Seed Patrick C. , Brauns Timothy , Gelfand Jeffrey A. , Hamblin Michael R. 
Published: May 2018

AbstractDrug-resistant urinary tract infections (UTIs) are difficult and sometimes impossible to treat. Many UTIs are caused by uropathogenic Escherichia coli (UPEC). We developed an intact rat model of UTI, by catheterizing female rats and introducing a bioluminescent UPEC strain into the female rat bladder which lasted for up to six days. We recently showed that antimicrobial photodynamic inactivation (aPDI) of a bacterial infection mediated by the well-known phenothiazinium salt, methylene blue (MB) could be strongly potentiated by addition of the non-toxic salt potassium iodide (KI). In the intact rat model we introduced MB into the bladder by catheter, followed by KI solution and delivered intravesicular illumination with a diffusing fiber connected to a 1 W 660 nm laser. Bioluminescent imaging of the bacterial burden was carried out during the procedure and for 6 days afterwards. Light-dose dependent loss of bioluminescence was observed with the combination of MB followed by KI, but recurrence of infection was seen the next day in some cases. aPDT with MB + KI gave a significantly shorter duration of infection compared to untreated controls. aPDT with MB alone was the least effective. No signs of aPDT damage to the bladder lining were detected. This procedure to treat urinary tract infections without antibiotics by using already approved pharmaceutical substances (MB and KI) may have clinical applicability, either initially as a stand-alone therapy, or as an adjunct to antibiotic therapy by a rapid and substantial reduction of the bacterial burden.
Matrix metalloproteinases (MMPs) mediate leukocyte recruitment during the inflammatory phase of zebrafish heart regeneration
Authors: Xu Shisan , Webb Sarah E. , Lau Terrence Chi Kong , Cheng Shuk Han 
Published: May 2018

AbstractIn zebrafish, the role of matrix metalloproteinases (MMPs) in the inflammatory phase of heart regeneration following cryoinjury remains poorly understood. Here, we demonstrated an increase in MMP enzymatic activity and elevated expression of mmp9 and mmp13 in the injured area (IA) of hearts from as early as 1 day post-cryoinjury (dpc). Treatment with the broad-spectrum MMP inhibitor, GM6001, during the first week after cryoinjury resulted in impaired heart regeneration, as indicated by the larger scar and reduced numbers of proliferating cardiomyocytes. GM6001 also significantly reduced the number of leukocytes to the IA at 0.5 dpc to 4 dpc. Specific inhibition of both MMP-9 and MMP-13 also resulted in impaired regeneration and leukocyte recruitment. However, chemokine rescue with recombinant CXCL8 and CCL2 restored the recruitment of macrophages and the cardiac regenerative capability in GM6001-treated fish. MMP-9 and MMP-13 cleaved zebrafish CXCL8 at the same site, and the truncated form was more chemotactic than the intact form. In contrast, CCL2 did not have an MMP-9 or MMP-13 cleavage site. Together, these data suggest that MMPs might play a key role in the inflammatory phase of heart regeneration in zebrafish, by mediating leukocyte recruitment via the activation of chemokines.
The Role of Electrostatic Repulsion on Increasing Surface Activity of Anionic Surfactants in the Presence of Hydrophilic Silica Nanoparticles
Authors: Vatanparast Hamid , Shahabi Farshid , Bahramian Alireza , Javadi Aliyar , Miller Reinhard 
Published: May 2018

AbstractHydrophilic silica nanoparticles alone are not surface active. They, however, develop a strong electrostatic interaction with ionic surfactants and consequently affect their surface behavior. We report the interfacial behavior of n-heptane/anionic-surfactant-solutions in the presence of hydrophilic silica nanoparticles. The surfactants are sodium dodecyl sulfate (SDS) and dodecyl benzene sulfonic acid (DBSA), and the diameters of the used particles are 9 and 30 nm. Using experimental tensiometry, we show that nanoparticles retain their non-surface-active nature in the presence of surfactants and the surface activity of surfactant directly increases with the concentration of nanoparticles. This fact was attributed to the electrostatic repulsive interaction between the negatively charged nanoparticles and the anionic surfactant molecules. The role of electrostatic repulsion on increasing surface activity of the surfactant has been discussed. Further investigations have been performed for screening the double layer charge of the nanoparticles in the presence of salt. Moreover, the hydrolysis of SDS molecules in the presence of silica nanoparticles and the interaction of nanoparticles with SDS inherent impurities have been studied. According to our experimental observations, silica nanoparticles alleviate the effects of dodecanol, formed by SDS hydrolysis, on the interfacial properties of SDS solution.
Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy
Authors: Chettimada Sukrutha , Lorenz David R. , Misra Vikas , Dillon Simon T. , Reeves R. Keith , Manickam Cordelia , Morgello Susan , Kirk Gregory D. , Mehta Shruti H. , Gabuzda Dana 
Published: May 2018

AbstractExosomes are nanovesicles released from most cell types including immune cells. Prior studies suggest exosomes play a role in HIV pathogenesis, but little is known about exosome cargo in relation to immune responses and oxidative stress. Here, we characterize plasma exosomes in HIV patients and their relationship to immunological and oxidative stress markers. Plasma exosome fractions were isolated from HIV-positive subjects on ART with suppressed viral load and HIV-negative controls. Exosomes were characterized by electron microscopy, nanoparticle tracking, immunoblotting, and LC-MS/MS proteomics. Plasma exosomes were increased in HIV-positive subjects compared to controls, and correlated with increased oxidative stress markers (cystine, oxidized cys-gly) and decreased PUFA (DHA, EPA, DPA). Untargeted proteomics detected markers of exosomes (CD9, CD63, CD81), immune activation (CD14, CRP, HLA-A, HLA-B), oxidative stress (CAT, PRDX1, PRDX2, TXN), and Notch4 in plasma exosomes. Exosomal Notch4 was increased in HIV-positive subjects versus controls and correlated with immune activation markers. Treatment of THP-1 monocytic cells with patient-derived exosomes induced expression of genes related to interferon responses and immune activation. These results suggest that exosomes in ART-treated HIV patients carry proteins related to immune activation and oxidative stress, have immunomodulatory effects on myeloid cells, and may have pro-inflammatory and redox effects during pathogenesis.
Osmotic modulation of chromatin impacts on efficiency and kinetics of cell fate modulation
Authors: Lima A. F. , May G. , Díaz-Colunga J. , Pedreiro S. , Paiva A. , Ferreira L. , Enver T. , Iborra F. J. , Pires das Neves R. 
Published: May 2018

AbstractChromatin structure is a major regulator of transcription and gene expression. Herein we explore the use of osmotic modulation to modify the chromatin structure and reprogram gene expression. In this study we use the extracellular osmotic pressure as a chromatin structure and transcriptional modulator. Hyposmotic modulation promotes chromatin loosening and induces changes in RNA polymerase II (Pol II) activity. The chromatin decondensation opens space for higher amounts of DNA engaged RNA Pol II. Hyposmotic modulation constitutes an alternative route to manipulate cell fate decisions. This technology was tested in model protocols of induced pluripotency and transdifferentiation in cells growing in suspension and adherent to substrates, CD34+umbilical-cord-blood (UCB), fibroblasts and B-cells. The efficiency and kinetics of these cell fate modulation processes were improved by transient hyposmotic modulation of the cell environment.
Assessment of ECG and respiration recordings from simulated emergency landings of ultra light aircraft
Authors: Bruna Ondřej , Levora Tomáš , Holub Jan 
Published: May 2018

AbstractPilots of ultra light aircraft have limited training resources, but with the use of low cost simulators it might be possible to train and test some parts of their training on the ground. The purpose of this paper is to examine possibility of stress inducement on a low cost flight simulator. Stress is assessed from electrocardiogram and respiration. Engine failure during flight served as a stress inducement stimuli. For one flight, pilots had access to an emergency navigation system. There were recorded some statistically significant changes in parameters regarding breathing frequency. Although no significant change was observed in ECG parameters, there appears to be an effect on respiration parameters. Physiological signals processed with analysis of variance suggest, that the moment of engine failure and approach for landing affected average breathing frequency. Presence of navigation interface does not appear to have a significant effect on pilots.
Inhibition of poly-LacNAc biosynthesis with release of CMP-Neu5Ac feedback inhibition increases the sialylation of recombinant EPO produced in CHO cells
Authors: Lee Chung-Geun , Oh Myung Jin , Park Seung-Yeol , An Hyun Joo , Kim Jung Hoe 
Published: May 2018

AbstractSialylation of recombinant therapeutic glycoproteins modulates their pharmacokinetic properties by affecting their in vivo half-life. N-glycan branching on glycoproteins increases the number of potential attachment sites for sialic acid. Here, we introduce a new approach for increasing the sialylation of recombinant human erythropoietin (rhEPO) produced in CHO cells by modulating poly-N-acetyllactosamine (poly-LacNAc) biosynthesis. We did not observe an increase in rhEPO sialylation, however, until the feedback inhibition by intracellular cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac), which is a limiting factor for sialylation, was released. Thus, we found that a combined approach inhibiting poly-LacNAc biosynthesis and releasing CMP-Neu5Ac feedback inhibition produces the most significant increase in rhEPO sialylation in metabolically engineered CHO cells. Furthermore, a detailed analysis of the resulting N-glycan structures using LC/MS revealed increased tri- and tetra- sialylated N-glycan structures accompanied by a reduction of di-sialylated N-glycan structures. These results validate our new approach for glycosylation engineering, and we expect this approach will be useful in future efforts to enhance the efficacy of other therapeutic glycoproteins.
Mechanical adaptation of trabecular bone morphology in the mammalian mandible
Authors: Watson Peter J. , Fitton Laura C. , Meloro Carlo , Fagan Michael J. , Gröning Flora 
Published: May 2018

AbstractAlveolar bone, together with the underlying trabecular bone, fulfils an important role in providing structural support against masticatory forces. Diseases such as osteoporosis or periodontitis cause alveolar bone resorption which weakens this structural support and is a major cause of tooth loss. However, the functional relationship between alveolar bone remodelling within the molar region and masticatory forces is not well understood. This study investigated this relationship by comparing mammalian species with different diets and functional loading (Felis catus, Cercocebus atys, Homo sapiens, Sus scrofa, Oryctolagus cuniculus, Ovis aries). We performed histomorphometric analyses of trabecular bone morphology (bone volume fraction, trabecular thickness and trabecular spacing) and quantified the variation of bone and tooth root volumes along the tooth row. A principal component analysis and non-parametric MANOVA showed statistically significant differences in trabecular bone morphology between species with contrasting functional loading, but these differences were not seen in sub-adult specimens. Our results support a strong, but complex link between masticatory function and trabecular bone morphology. Further understanding of a potential functional relationship could aid the diagnosis and treatment of mandibular diseases causing alveolar bone resorption, and guide the design and evaluation of dental implants.
Discovery and functional characterisation of a luqin-type neuropeptide signalling system in a deuterostome
Authors: Yañez-Guerra Luis Alfonso , Delroisse Jérôme , Barreiro-Iglesias Antón , Slade Susan E. , Scrivens James H. , Elphick Maurice R. 
Published: May 2018

AbstractNeuropeptides are diverse and evolutionarily ancient regulators of physiological/behavioural processes in animals. Here we have investigated the evolution and comparative physiology of luqin-type neuropeptide signalling, which has been characterised previously in protostomian invertebrates. Phylogenetic analysis indicates that luqin-type receptors and tachykinin-type receptors are paralogous and probably originated in a common ancestor of the Bilateria. In the deuterostomian lineage, luqin-type signalling has been lost in chordates but interestingly it has been retained in ambulacrarians. Therefore, here we characterised luqin-type signalling for the first time in an ambulacrarian – the starfish Asterias rubens (phylum Echinodermata). A luqin-like neuropeptide with a C-terminal RWamide motif (ArLQ; EEKTRFPKFMRW-NH2) was identified as the ligand for two luqin-type receptors in A. rubens, ArLQR1 and ArLQR2. Furthermore, analysis of the expression of the ArLQ precursor using mRNA in situ hybridisation revealed expression in the nervous system, digestive system and locomotory organs (tube feet) and in vitro pharmacology revealed that ArLQ causes dose-dependent relaxation of tube feet. Accordingly, previous studies have revealed that luqin-type signalling regulates feeding and locomotor activity in protostomes. In conclusion, our phylogenetic analysis combined with characterisation of luqin-type signalling in a deuterostome has provided new insights into neuropeptide evolution and function in the animal kingdom.
Tumor heterogeneity of pancreas head cancer assessed by CT texture analysis: association with survival outcomes after curative resection
Authors: Yun Gabin , Kim Young Hoon , Lee Yoon Jin , Kim Bohyoung , Hwang Jin-Hyeok , Choi Dong Joon 
Published: May 2018

AbstractThe value of image based texture features as a powerful method to predict prognosis and assist clinical management in cancer patients has been established recently. However, texture analysis using histograms and grey-level co-occurrence matrix in pancreas cancer patients has rarely been reported. We aimed to analyze the association of survival outcomes with texture features in pancreas head cancer patients. Eighty-eight pancreas head cancer patients who underwent preoperative CT images followed by curative resection were included. Texture features using different filter values were obtained. The texture features of average, contrast, correlation, and standard deviation with no filter, and fine to medium filter values as well as the presence of nodal metastasis were significantly different between the recurred (n = 70, 79.5%) and non-recurred group (n = 18, 20.5%). In the multivariate Cox regression analysis, lower standard deviation and contrast and higher correlation with lower average value representing homogenous texture were significantly associated with poorer DFS (disease free survival), along with the presence of lymph node metastasis. Texture parameters from routinely performed pre-operative CT images could be used as an independent imaging tool for predicting the prognosis in pancreas head cancer patients who underwent curative resection.
Tortuous Pore Path Through the Glaucomatous Lamina Cribrosa
Authors: Wang Bo , Lucy Katie A. , Schuman Joel S. , Sigal Ian A. , Bilonick Richard A. , Lu Chen , Liu Jonathan , Grulkowski Ireneusz , Nadler Zachary , Ishikawa Hiroshi , Kagemann Larry , Fujimoto James G. , Wollstein Gadi 
Published: May 2018

AbstractThe lamina cribrosa is a primary site of damage in glaucoma. While mechanical distortion is hypothesized to cause reduction of axoplasmic flow, little is known about how the pores, which contains the retinal ganglion cell axons, traverse the lamina cribrosa. We investigated lamina cribrosa pore paths in vivo to quantify differences in tortuosity of pore paths between healthy and glaucomatous eyes. We imaged 16 healthy, 23 glaucoma suspect and 48 glaucomatous eyes from 70 subjects using a swept source optical coherence tomography system. The lamina cribrosa pores were automatically segmented using a previously described segmentation algorithm. Individual pore paths were automatically tracked through the depth of the lamina cribrosa using custom software. Pore path convergence to the optic nerve center and tortuosity was quantified for each eye. We found that lamina cribrosa pore pathways traverse the lamina cribrosa closer to the optic nerve center along the depth of the lamina cribrosa regardless of disease severity or diagnostic category. In addition, pores of glaucoma eyes take a more tortuous path through the lamina cribrosa compared to those of healthy eyes, suggesting a potential mechanism for reduction of axoplasmic flow in glaucoma.
Periodical reactivation under the effect of caffeine attenuates fear memory expression in rats
Authors: Pedraza Lizeth K. , Sierra Rodrigo O. , Lotz Fernanda N. , de Oliveira Alvares Lucas 
Published: May 2018

AbstractIn the last decade, several studies have shown that fear memories can be attenuated by interfering with reconsolidation. However, most of the pharmacological agents used in preclinical studies cannot be administered to humans. Caffeine is one of the world’s most popular psychoactive drugs and its effects on cognitive and mood states are well documented. Nevertheless, the influence of caffeine administration on fear memory processing is not as clear. We employed contextual fear conditioning in rats and acute caffeine administration under a standard memory reconsolidation protocol or periodical memory reactivation. Additionally, potential rewarding/aversion and anxiety effects induced by caffeine were evaluated by conditioning place preference or open field, respectively. Caffeine administration was able to attenuate weak fear memories in a standard memory reconsolidation protocol; however, periodical memory reactivation under caffeine effect was necessary to attenuate strong and remote memories. Moreover, caffeine promoted conditioned place preference and anxiolytic-like behavior, suggesting that caffeine weakens the initial learning during reactivation through counterconditioning mechanisms. Thus, our study shows that rewarding and anxiolytic effects of caffeine during fear reactivation can change the emotional valence of fear memory. It brings a new promising pharmacological approach based on drugs widely used such as caffeine to treat fear-related disorders.
Tissue distribution and cell tropism of Brucella canis in naturally infected canine foetuses and neonates
Authors: de Souza Tayse Domingues , de Carvalho Tatiane Furtado , Mol Juliana Pinto da Silva , Lopes João Vítor Menezes , Silva Monique Ferreira , da Paixão Tatiane Alves , Santos Renato Lima 
Published: May 2018

AbstractBrucella canis infection is an underdiagnosed zoonotic disease. Knowledge about perinatal brucellosis in dogs is extremely limited, although foetuses and neonates are under risk of infection due to vertical transmission. In this study, immunohistochemistry was used to determine tissue distribution and cell tropism of B. canis in canine foetuses and neonates. Diagnosis of B. canis in tissues of naturally infected pups was based on PCR and sequencing of amplicons, bacterial isolation, and immunohistochemistry, whose specificity was confirmed by laser capture microdissection. PCR positivity among 200 puppies was 21%, and nine isolates of B. canis were obtained. Tissues from 13 PCR-positive puppies (4 stillborn and 9 neonates) presented widespread immunolabeling. Stomach, intestines, kidney, nervous system, and umbilicus were positive in all animals tested. Other frequently infected organs included the liver (92%), lungs (85%), lymph nodes (69%), and spleen (62%). Immunolabeled coccobacilli occurred mostly in macrophages, but they were also observed in erythrocytes, epithelial cells of gastrointestinal mucosa, renal tubules, epidermis, adipocytes, choroid plexus, ependyma, neuroblasts, blood vessels endothelium, muscle cells, and in the intestinal lumen. These results largely expand our knowledge about perinatal brucellosis in the dog, clearly demonstrating a pantropic distribution of B. canis in naturally infected foetuses and neonates.
Tuning the electrical properties of the p-type transparent conducting oxide Cu1−xCr1+xO2 by controlled annealing
Authors: Lunca-Popa P. , Afonso J. , Grysan P. , Crêpellière J. , Leturcq R. , Lenoble D. 
Published: May 2018

AbstractOff-stoichiometric copper chromium oxide delafossite received lately a great interest due to its high p-type electrical conductivity and adequate optical transmittance in the visible range. However, for a suitable integration in active devices such as p-n junctions, transistors or optoelectronic devices, the electronic properties must be efficiently tailored. Here, post-deposition thermal treatment is proven as an adequate approach for finely controlling the electrical properties of this former degenerate semiconducting material. The energetics of the annealing process are investigated using two different approaches, as a function of the annealing temperature and as a function of the annealing time, allowing the accurate determination of the activation energy of the annealing of defects. By using this method, the electrical carrier concentration was varied in the 1021 – 1017 cm−3 range while the recorded changes in the drift mobility covered three orders of magnitude. Moreover, we demonstrate the ability to accurately manipulate the Fermi level of such materials, which is of great importance in controlling the carrier injection and extraction in optoelectronic active layers.