bluuebunny/crossref_metadata_2025_split huggingface dataset:
Embryonic development of selectively vulnerable neurons in Parkinson’s disease
Authors: Oliveira Miguel A. P. , Balling Rudi , Smidt Marten P. , Fleming Ronan M. T. 
Published: June 2017

AbstractA specific set of brainstem nuclei are susceptible to degeneration in Parkinson’s disease. We hypothesise that neuronal vulnerability reflects shared phenotypic characteristics that confer selective vulnerability to degeneration. Neuronal phenotypic specification is mainly the cumulative result of a transcriptional regulatory program that is active during the development. By manual curation of the developmental biology literature, we comprehensively reconstructed an anatomically resolved cellular developmental lineage for the adult neurons in five brainstem regions that are selectively vulnerable to degeneration in prodromal or early Parkinson’s disease. We synthesised the literature on transcription factors that are required to be active, or required to be inactive, in the development of each of these five brainstem regions, and at least two differentially vulnerable nuclei within each region. Certain transcription factors, e.g., Ascl1 and Lmx1b, seem to be required for specification of many brainstem regions that are susceptible to degeneration in early Parkinson’s disease. Some transcription factors can even distinguish between differentially vulnerable nuclei within the same brain region, e.g., Pitx3 is required for specification of the substantia nigra pars compacta, but not the ventral tegmental area. We do not suggest that Parkinson’s disease is a developmental disorder. In contrast, we consider identification of shared developmental trajectories as part of a broader effort to identify the molecular mechanisms that underlie the phenotypic features that are shared by selectively vulnerable neurons. Systematic in vivo assessment of fate determining transcription factors should be completed for all neuronal populations vulnerable to degeneration in early Parkinson’s disease.
DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections
Authors: Elliott Sarah T. C. , Kallewaard Nicole L. , Benjamin Ebony , Wachter-Rosati Leslie , McAuliffe Josephine M. , Patel Ami , Smith Trevor R. F. , Schultheis Katherine , Park Daniel H. , Flingai Seleeke , Wise Megan C. , Mendoza Janess , Ramos Stephanie , Broderick Kate E. , Yan Jian , Humeau Laurent M. , Sardesai Niranjan Y. , Muthumani Kar , Zhu Qing , Weiner David B. 
Published: June 2017

AbstractInfluenza virus remains a significant public health threat despite innovative vaccines and antiviral drugs. A major limitation to current vaccinations and therapies against influenza virus is pathogenic diversity generated by shift and drift. A simple, cost-effective passive immunization strategy via in vivo production of cross-protective antibody molecules may augment existing vaccines and antiviral drugs in seasonal and pandemic outbreaks. We engineered synthetic plasmid DNA to encode two novel and broadly cross-protective monoclonal antibodies targeting influenza A and B. We utilized enhanced in vivo delivery of these plasmid DNA-encoded monoclonal antibody (DMAb) constructs and show that this strategy induces robust levels of functional antibodies directed against influenza A and B viruses in mouse sera. Mice receiving a single inoculation with anti-influenza A DMAb survive lethal Group 1 H1 and Group 2 H3 influenza A challenges, while inoculation with anti-influenza B DMAb yields protection against lethal Victoria and Yamagata lineage influenza B morbidity and mortality. Furthermore, these two DMAbs can be delivered coordinately resulting in exceptionally broad protection against both influenza A and B. We demonstrate this protection is similar to that achieved by conventional protein antibody delivery. DMAbs warrant further investigation as a novel immune therapy platform with distinct advantages for sustained immunoprophylaxis against influenza.
Mapping the Glyco-Gold Nanoparticles of Different Shapes Toxicity, Biodistribution and Sequestration in Adult Zebrafish
Authors: Sangabathuni Sivakoti , Murthy Raghavendra Vasudeva , Chaudhary Preeti Madhukar , Subramani Balamurugan , Toraskar Suraj , Kikkeri Raghavendra 
Published: June 2017

AbstractGlyconanotechnology offers a broad range of applications across basic and translation research. Despite the tremendous progress in glyco-nanomaterials, there is still a huge gap between the basic research and therapeutic applications of these molecules. It has been reported that complexity and the synthetic challenges in glycans synthesis, the cost of the high order in vivo models and large amount of sample consumptions limited the effort to translate the glyco-nanomaterials into clinical applications. In this regards, several promising simple animal models for preliminary, quick analysis of the nanomaterials activities has been proposed. Herein, we have studied a systematic evaluation of the toxicity, biodistribution of fluorescently tagged PEG and mannose-capped gold nanoparticles (AuNPs) of three different shapes (sphere, rod, and star) in the adult zebrafish model, which could accelerate and provide preliminary results for further experiments in the higher order animal system. ICP-MS analysis and confocal images of various zebrafish organs revealed that rod-AuNPs exhibited the fast uptake. While, star-AuNPs displayed prolong sequestration, demonstrating its potential therapeutic efficacy in drug delivery.
Intracellular targeting of annexin A2 inhibits tumor cell adhesion, migration, and in vivo grafting
Authors: Staquicini Daniela I. , Rangel Roberto , Guzman-Rojas Liliana , Staquicini Fernanda I. , Dobroff Andrey S. , Tarleton Christy A. , Ozbun Michelle A. , Kolonin Mikhail G. , Gelovani Juri G. , Marchiò Serena , Sidman Richard L. , Hajjar Katherine A. , Arap Wadih , Pasqualini Renata 
Published: June 2017

AbstractCytoskeletal-associated proteins play an active role in coordinating the adhesion and migration machinery in cancer progression. To identify functional protein networks and potential inhibitors, we screened an internalizing phage (iPhage) display library in tumor cells, and selected LGRFYAASG as a cytosol-targeting peptide. By affinity purification and mass spectrometry, intracellular annexin A2 was identified as the corresponding binding protein. Consistently, annexin A2 and a cell-internalizing, penetratin-fused version of the selected peptide (LGRFYAASG-pen) co-localized and specifically accumulated in the cytoplasm at the cell edges and cell-cell contacts. Functionally, tumor cells incubated with LGRFYAASG-pen showed disruption of filamentous actin, focal adhesions and caveolae-mediated membrane trafficking, resulting in impaired cell adhesion and migration in vitro. These effects were paralleled by a decrease in the phosphorylation of both focal adhesion kinase (Fak) and protein kinase B (Akt). Likewise, tumor cells pretreated with LGRFYAASG-pen exhibited an impaired capacity to colonize the lungs in vivo in several mouse models. Together, our findings demonstrate an unrecognized functional link between intracellular annexin A2 and tumor cell adhesion, migration and in vivo grafting. Moreover, this work uncovers a new peptide motif that binds to and inhibits intracellular annexin A2 as a candidate therapeutic lead for potential translation into clinical applications.
Network model predicts that CatSper is the main Ca2+ channel in the regulation of sea urchin sperm motility
Authors: Espinal-Enríquez Jesús , Priego-Espinosa Daniel Alejandro , Darszon Alberto , Beltrán Carmen , Martínez-Mekler Gustavo 
Published: June 2017

AbstractSpermatozoa sea urchin swimming behaviour is regulated by small peptides from the egg outer envelope. Speract, such a peptide, after binding to its receptor in Strongylocentrotus purpuratus sperm flagella, triggers a signaling pathway that culminates with a train of intracellular calcium oscillations, correlated with changes in sperm swimming pattern. This pathway has been widely studied but not fully characterized. Recent work on Arbacia punctulata sea urchin spermatozoa has documented the presence of the Ca2+ CatSper channel in their flagella and its involvement in chemotaxis. However, if other calcium channels participate in chemotaxis remains unclear. Here, based on an experimentally-backed logical network model, we conclude that CatSper is fundamental in the S. purpuratus speract-activated sea urchin sperm signaling cascade, although other Ca2+ channels could still be relevant. We also present for the first time experimental corroboration of its active presence in S. purpuratus sperm flagella. We argue, prompted by in silico knock-out calculations, that CatSper is the main generator of calcium oscillations in the signaling pathway and that other calcium channels, if present, have a complementary role. The approach adopted here allows us to unveil processes, which are hard to detect exclusively by experimental procedures.
A Microfluidic Chip for Detecting Cholangiocarcinoma Cells in Human Bile
Authors: Hung Lien-Yu , Chiang Nai-Jung , Tsai Wei-Chun , Fu Chien-Yu , Wang Yu-Chun , Shan Yan-Shen , Lee Gwo-Bin 
Published: June 2017

AbstractCholangiocarcinoma (CCA), a biliary tract malignancy, accounts for 20% of all liver cancers. There are several existing methods for diagnosis of CCA, though they are generally expensive, laborious, and suffer from low detection rates. Herein we first developed a means of partially purifying human bile for consequent injection into a microfluidic chip. Then, the novel microfluidic system, which featured 1) a cell capture module, 2) an immunofluorescence (IF) staining module featuring two CCA-specific biomarkers, and 3) an optical detection module for visualization of antibody probes bound to these CCA marker proteins, was used to detect bile duct cancer cells within partially purified bile samples. As a proof of concept, CCA cells were successfully captured and identified from CCA cell cultures, blood samples inoculated with CCA cells, and clinical bile specimens. In 7.5 ml of bile, this system could detect >2, 0, and 1 positive cells in advanced stage patients, healthy patients, and chemotherapy-treated patients, respectively. In conclusion, our microfluidic system could be a promising tool for detection of cancer cells in bile, even at the earliest stages of CCA when cancer cells are at low densities relative to the total population of epithelial cells.
Novel loop-mediated isothermal amplification (LAMP) assay with a universal QProbe can detect SNPs determining races in plant pathogenic fungi
Authors: Ayukawa Yu , Hanyuda Saeri , Fujita Naoko , Komatsu Ken , Arie Tsutomu 
Published: June 2017

AbstractTomato wilt pathogen Fusarium oxysporum f. sp. lycopersici (Fol) is grouped into three races based on their pathogenicity to different host cultivars. Rapid detection and discrimination of Fol races in field soils is important to prevent tomato wilt disease. Although five types of point mutations in secreted in xylem 3 (SIX3) gene, which are characteristic of race 3, have been reported as a molecular marker for the race, detection of these point mutations is laborious. The aim of this study is to develop a rapid and accurate method for the detection of point mutations in SIX3 of Fol. Loop-mediated isothermal amplification (LAMP) of SIX3 gene with the universal QProbe as well as two joint DNAs followed by annealing curve analysis allowed us to specifically detect Fol and discriminate race 3 among other races in about one hour. Our developed method is applicable for detection of races of other plant pathogenic fungi as well as their pesticide-resistant mutants that arise through point mutations in a particular gene.
Identification of Jak-STAT signaling involvement in sarcoidosis severity via a novel microRNA-regulated peripheral blood mononuclear cell gene signature
Authors: Zhou Tong , Casanova Nancy , Pouladi Nima , Wang Ting , Lussier Yves , Knox Kenneth S. , Garcia Joe G. N. 
Published: June 2017

AbstractSarcoidosis is a granulomatous lung disorder of unknown cause. The majority of individuals with sarcoidosis spontaneously achieve full remission (uncomplicated sarcoidosis), however, ~20% of sarcoidosis-affected individuals experience progressive lung disease or cardiac and nervous system involvement (complicated sarcoidosis). We investigated peripheral blood mononuclear cell (PBMC) microRNA and protein-coding gene expression data from healthy controls and patients with uncomplicated or complicated sarcoidosis. We identified 46 microRNAs and 1,559 genes that were differentially expressed across a continuum of sarcoidosis severity (healthy control → uncomplicated sarcoidosis → complicated sarcoidosis). A total of 19 microRNA-mRNA regulatory pairs were identified within these deregulated microRNAs and mRNAs, which consisted of 17 unique protein-coding genes yielding a 17-gene signature. Pathway analysis of the 17-gene signature revealed Jak-STAT signaling pathway as the most significantly represented pathway. A severity score was assigned to each patient based on the expression of the 17-gene signature and a significant increasing trend in the severity score was observed from healthy control, to uncomplicated sarcoidosis, and finally to complicated sarcoidosis. In addition, this microRNA-regulated gene signature differentiates sarcoidosis patients from healthy controls in independent validation cohorts. Our study suggests that PBMC gene expression is useful in diagnosis of sarcoidosis.
A high resolution melting method for the molecular identification of the potentially toxic diatom Pseudo-nitzschia spp. in the Mediterranean Sea
Authors: Pugliese Laura , Casabianca Silvia , Perini Federico , Andreoni Francesca , Penna Antonella 
Published: June 2017

AbstractThe aim of this study was to develop and validate a high resolution melting (HRM) method for the rapid, accurate identification of the various harmful diatom Pseudo-nitzschia species in marine environments. Pseudo-nitzschia has a worldwide distribution and some species are toxic, producing the potent domoic acid toxin, which poses a threat to both human and animal health. Hence, it is important to identify toxic Pseudo-nitzschia species. A pair of primers targeting the LSU rDNA of the genus Pseudo-nitzschia was designed for the development of the assay and its specificity was validated using 22 control DNAs of the P. calliantha, P. delicatissima/P. arenysensis complex and P. pungens. The post-PCR HRM assay was applied to numerous unidentified Pseudo-nitzschia strains isolated from the northwestern Adriatic Sea (Mediterranean Sea), and it was able to detect and discriminate three distinct Pseudo-nitzschia taxa from unidentified samples. Moreover, the species-specific identification of Pseudo-nitzschia isolates by the HRM assay was consistent with phylogenetic analyses. The HRM assay was specific, robust and rapid when applied to high numbers of cultured samples in order to taxonomically identify Pseudo-nitzschia isolates recovered from environmental samples.
Clinical Features of Congenital and Developmental Cataract in East China: A Five-year Retrospective Review
Authors: Zhu Xiangjia , Du Yu , He Wenwen , Sun Ting , Zhang Yinglei , Chang Ruiqi , Zhang Keke , Lu Yi 
Published: June 2017

AbstractCongenital/developmental cataract is a significant cause of blindness in children worldwide. Full knowledge of clinical features is essential for early diagnosis and proper treatment to prevent irreversible visual impairment. We conducted a retrospective chart review on 520 congenital/developmental cataract cases based on a five-year clinical data from Eye and ENT Hospital of Fudan University, Shanghai, China. Clinical features including age at the surgery, chief complaints, interval between initial identification of cataract-related manifestations and surgery, etc. were summarized. 56.3% of children were bilateral. The age at surgery ranged from 0.25 to 17.4 years, only 9.2% receiving surgery below 1 year. Interval between initial identification of manifestations and surgery ranged from 2 days to 17 years. Concomitant congenital abnormalities were present in 67 patients, with persistent hyperplastic primary vitreous and congenital heart disease as the most frequent ocular and systemic disorders. Strabismus and nystagmus were seen in 20.6% and 11.9% of patients. In bilateral cataract patients with strabismus, axial lengths of esotropia-affected eyes were statistically shorter than exotropia-affected eyes. These findings provide information on characteristics of congenital/developmental cataract in China and may assist in achievement of comprehensive treating strategies in these cases.
Single microtubules and small networks become significantly stiffer on short time-scales upon mechanical stimulation
Authors: Koch Matthias D. , Schneider Natalie , Nick Peter , Rohrbach Alexander 
Published: June 2017

AbstractThe transfer of mechanical signals through cells is a complex phenomenon. To uncover a new mechanotransduction pathway, we study the frequency-dependent transport of mechanical stimuli by single microtubules and small networks in a bottom-up approach using optically trapped beads as anchor points. We interconnected microtubules to linear and triangular geometries to perform micro-rheology by defined oscillations of the beads relative to each other. We found a substantial stiffening of single filaments above a characteristic transition frequency of 1–30 Hz depending on the filament’s molecular composition. Below this frequency, filament elasticity only depends on its contour and persistence length. Interestingly, this elastic behavior is transferable to small networks, where we found the surprising effect that linear two filament connections act as transistor-like, angle dependent momentum filters, whereas triangular networks act as stabilizing elements. These observations implicate that cells can tune mechanical signals by temporal and spatial filtering stronger and more flexibly than expected.
Towards conductive textiles: coating polymeric fibres with graphene
Authors: Neves Ana I. S. , Rodrigues Daniela P. , De Sanctis Adolfo , Alonso Elias Torres , Pereira Maria S. , Amaral Vitor S. , Melo Luis V. , Russo Saverio , de Schrijver Isabel , Alves Helena , Craciun Monica F. 
Published: June 2017

AbstractConducting fibres are essential to the development of e-textiles. We demonstrate a method to make common insulating textile fibres conductive, by coating them with graphene. The resulting fibres display sheet resistance values as low as 600 Ωsq−1, demonstrating that the high conductivity of graphene is not lost when transferred to textile fibres. An extensive microscopic study of the surface of graphene-coated fibres is presented. We show that this method can be employed to textile fibres of different materials, sizes and shapes, and to different types of graphene. These graphene-based conductive fibres can be used as a platform to build integrated electronic devices directly in textiles.
Automatic inhibitory function in the human somatosensory and motor cortices: An MEG-MRS study
Authors: Cheng Chia-Hsiung , Tsai Shang-Yueh , Liu Chia-Yih , Niddam David M. 
Published: June 2017

AbstractWhile the automatic inhibitory function of the human cerebral cortex has been extensively investigated by means of electrophysiological recordings, the corresponding modulating neurochemical mechanisms remain unclear. We aimed to examine whether the primary somatosensory (SI) and primary motor cortical (MI) inhibitory function is associated with endogenous GABA levels. Eighteen young participants received paired-pulse and single-pulse electrical stimulation to the median nerve during magnetoencephalographic recordings. The SI sensory gating (SG), considered as an automatic inhibitory ability, was measured as the amplitude ratio of Stimulus 2 over Stimulus 1, in the paired-pulse paradigm. In addition, stimulus-induced beta activity, considered to originate from MI and also to be related to inhibitory function, was estimated using the single-pulse paradigm. The GABA+ concentration of the sensorimotor cortex was acquired from each subject by using magnetic resonance spectroscopy (MRS). A lower SG ratio in SI was significantly associated with an increased beta power in MI. More importantly, the beta rebound power, but not SI SG ratio, was positively correlated with GABA+ concentration. Our findings show a tight functional relationship between SI and MI during processing of automatic inhibition. GABA+ levels appear to be more closely related to the automatic inhibitory function of MI than SI.
Self-diploidization of human haploid parthenogenetic embryos through the Rho pathway regulates endomitosis and failed cytokinesis
Authors: Leng Lizhi , Ouyang Qi , Kong Xiangyi , Gong Fei , Lu Changfu , Zhao Lei , Shi Yun , Cheng Dehua , Hu Liang , Lu Guangxiu , Lin Ge 
Published: June 2017

AbstractA diploid genome is necessary for normal mammalian development, thus haploid parthenogenetic embryos undergo frequent self-diploidization during preimplantation development; however, the underlying mechanism is unclear. In this study, time-lapse recording revealed that human haploid parthenotes (HPs) undergo self-diploidization via failed cytokinesis (FC) and endomitosis (EM). The frequencies of FC/EM were significantly higher in HPs than in normal fertilized embryos (26.3% vs. 1.6%, P < 0.01; 19.7% vs. 0, P < 0.01), and above 90% of FC/EM occurred at the first cell cycle in HPs. Fluorescent in situ hybridization of chromosome 16,18 and X in HPs identified diploid recovery after the appearance of FC/EM, and FC/EM HPs showed improved blastocyst formation compared with non-FC/EM HPs (18.8% and 40.0% vs. 15.4%, P > 0.05). In 66.7% of the 1-cell stage HPs, furrow ingression was not observed during the time for normal cleavage, and both immunostaining and gene expression analysis of 1-cell stage HPs revealed the absence or down-regulation of several key genes of the Rho pathway, which regulates cytomitosis. Our results suggested that the major mechanism for self-diploidization is Rho pathway inhibition leading to FC/EM in the first cell cycle, and fine-tuning of this signalling pathway may help to generate stable haploid embryos for stem cell biology studies.
Metabolische Konsequenzen der Peritonealdialyse
Authors: Girndt Matthias 
Published: June 2017

ZusammenfassungZur Behandlung der terminalen Niereninsuffizienz kann alternativ zur Hämodialyse auch die Peritonealdialyse eingesetzt werden. Hierbei wird die Bauchhöhle mit 2 – 3 l Dialyseflüssigkeit gefüllt, die in regelmäßigen Abständen gewechselt wird. Um einen osmotischen Gradienten aufzubauen und dem Körper Flüssigkeit entziehen zu können, wird der Dialyseflüssigkeit Glukose zugesetzt. Ein Teil dieser Glukose wird während der Behandlung resorbiert und beeinflusst den Kohlenhydratstoffwechsel des Patienten. Dies ist vor allem bei Diabetikern bedeutsam, die aber bei geeigneter Steuerung durchaus mit Peritonealdialyse behandelt werden können.Patienten weisen unterschiedliche Glukosetransportcharakteristika auf. Die jeweilige Dialyseverordnung muss die Transportcharakteristik berücksichtigen und hat Einfluss auf die Glukoseresorption. Zur Verringerung der Glukoseaufnahme kann auch die Polyglukose Icodextrin als osmotisches Agens eingesetzt werden. Es gibt Hinweise, dass dies zu einer besseren Stoffwechselführung bei Diabetikern beitragen kann. Allerdings sind diagnostische Besonderheiten zu beachten, da Icodextrin das Glukosemonitoring des Diabetikers beeinflussen kann.