bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the role of GSK3 in the mitotic checkpoint
Authors: Rashid M. S. , Mazur T. , Ji W. , Liu S. T. , Taylor W. R. 
Published: September 2018

AbstractThe mitotic checkpoint ensures proper chromosome segregation; defects in this checkpoint can lead to aneuploidy, a hallmark of cancer. The mitotic checkpoint blocks progression through mitosis as long as chromosomes remain unattached to spindle microtubules. Unattached kinetochores induce the formation of a mitotic checkpoint complex (MCC) composed of Mad2, BubR1, Bub1 and Bub3 which inhibits anaphase onset. Spindle toxins induce prolonged mitotic arrest by creating persistently unattached kinetochores which trigger MCC formation. We find that the multifunctional ser/thr kinase, glycogen synthase kinase 3 (GSK3) is required for a strong mitotic checkpoint. Spindle toxin-induced mitotic arrest is relieved by GSK3 inhibitors SB 415286 (SB), RO 318220 (RO) and lithium chloride. Similarly, targeting GSK3β with knockout or RNAi reduced mitotic arrest in the presence of Taxol. GSK3 was required for optimal localization of Mad2, BubR1, and Bub1 at kinetochores and for optimal assembly of the MCC in spindle toxin-arrested cells. The WNT- and PI3K/Akt signaling pathways negatively regulate GSK3β activity. Inhibition of WNT and PI3K/Akt signaling, in the presence of Taxol, induced a longer mitotic arrest compared to Taxol alone. Our observations provide novel insight into the regulation of the mitotic checkpoint and its connection to growth-signaling pathways.
Crystal structure of FlgL and its implications for flagellar assembly
Authors: Hong Ho Jeong , Kim Tae Hee , Song Wan Seok , Ko Hyun-Jeong , Lee Geun-Shik , Kang Seung Goo , Kim Pyeung-Hyeun , Yoon Sung-il 
Published: September 2018

AbstractBacteria move toward attractants and away from repellants by rotating their flagellum. The bacterial flagellum assembles through the ordered organization of more than 30 different proteins. Among the diverse flagellar proteins, FlgL forms the junction between the hook and the filament in the flagellum together with FlgK and provides a structural base where flagellin, a filament-forming protein, is inserted for the initiation of filament elongation. However, the functional and structural information available for FlgL is highly limited. To provide structural insights into the cross-linkage between the FlgL junction and the flagellin filament, we determined the crystal structures of FlgL from gram-positive Bacillus cereus (bcFlgL) and gram-negative Xanthomonas campestris (xcFlgL). bcFlgL contains one domain (D1), whereas xcFlgL adopts a two-domain structure that consists of the D1 and D2 domains. The constant D1 domain of FlgL adopts a rod structure that is generated by four longitudinal segments. This four-segment structure is recapitulated in filament and junction proteins but not in hook and rod proteins, allowing us to propose a junction-filament assembly mechanism based on a quasi-homotypic interaction. The D2 domain of xcFlgL resembles that of another junction protein, FlgK, suggesting the structural and functional relatedness of FlgL and FlgK.
Functional Studies of Anodic Oxidized β-Ti-28Nb-11Ta-8Zr Alloy for Mechanical, In-vitro and Antibacterial Capability
Authors: Lin Hsin-I , Kuo Yu-Ming , Hu Chun-Chih , Lee Mu-Huan , Chen Ling-Hsiang , Li Chung-Tien , Wong Tze-Hong , Yen Ta-Jen 
Published: September 2018

AbstractWe developed an osseocompatible β-type Ti-28Nb-11Ta-8Zr (TNTZ) alloy that displays the excellent elastic modulus, cellular response, corrosion resistance and antibacterial capability demanded for bone-mimetic materials. The TNTZ alloy exhibited an elastic modulus of 49 GPa, which approximates that of human bones and prevent stress shielding effects. A further anodic oxidation and subsequent post-annealing modification formed a crystalline nanoporous TNTZ oxide layer (NPTNTZO(c)) on the alloy surface, potentially promoting interlocking with the extracellular matrix of bone cells and cell proliferation. Osteoblast viability tests also verified that NPTNTZO(c) enhanced cell growth more significantly than that of flat TNTZ. In addition, potentiodynamic polarization tests in Hanks’ balanced salt solution (HBSS) revealed that both TNTZ and NPTNTZO(c) exhibited better corrosion resistance than commercial pure titanium. Finally, NPTNTZO(c) reinforced with silver nanoparticles (NPTNTZO(c)/AgNPs) intensified the antibacterial efficiency againstPseudomonas aeruginosa,Staphylococcus aureusandEscherichia colifor 8 h with antibacterial efficiencies of 87.82%, 97.68%, and 93.90%, respectively, facilitating infection prevention during surgery and recovery stages.
Transcriptional Regulatory Networks in Hepatitis C Virus-induced Hepatocellular Carcinoma
Authors: Zahra Marwa , Azzazy Hassan , Moustafa Ahmed 
Published: September 2018

AbstractUnderstanding the transcriptional regulatory elements that influence the progression of liver disease in the presence of hepatitis C virus (HCV) infection is critical for the development of diagnostic and therapeutic approaches. Systems biology provides a roadmap by which these elements may be integrated. In this study, a previously published dataset of 124 microarray samples was analyzed in order to determine differentially expressed genes across four tissue types/conditions (normal, cirrhosis, cirrhosis HCC, and HCC). Differentially expressed genes were assessed for their functional clustering and those genes were annotated with their potential transcription factors and miRNAs. Transcriptional regulatory networks were constructed for each pairwise comparison between the 4 tissue types/conditions. Based on our analysis, it is predicted that the disruption in the regulation of transcription factors such as AP-1, PPARγ, and NF-κB could contribute to the liver progression from cirrhosis to steatosis and eventually to HCC. Whereas the condition of the liver digresses, the downregulation of miRNAs’ (such as miR-27, Let-7, and miR-106a) expression makes the transition of the liver through each pathological stage more apparent. This preliminary data can be used to guide future experimental work. An understanding of the transcriptional regulatory attributes acts as a road map to help design interference strategies in order to target the key regulators of progression of HCV induced HCC.
Identification of mesothelioma-specific sialylated epitope recognized with monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1
Authors: Matsuura Rieko , Kaji Hiroyuki , Tomioka Azusa , Sato Takashi , Narimatsu Hisashi , Moriwaki Yasuhiro , Misawa Hidemi , Imai Kohzoh , Tsuji Shoutaro 
Published: September 2018

AbstractThe anti-mesothelioma mAb SKM9-2 recognizes the sialylated protein HEG homolog 1 (HEG1). HEG1 is a 400 kDa mucin-like membrane protein found on mesothelioma. SKM9-2 can detect mesothelioma more specifically and sensitively than other antibodies against current mesothelioma markers; therefore, SKM9-2 would be likely useful for the precise detection and diagnosis of malignant mesothelioma. In the present study, we investigated the epitope of SKM9-2. We analyzed the binding of SKM9-2 to truncated HEG1 and candidate epitope-fused glycosylphosphatidylinositol-anchor proteins. The epitope of SKM9-2 was identified as an O-glycosylated region, 893-SKSPSLVSLPT-903, in HEG1. An alanine scanning assay of the epitope showed that SKM9-2 bound to a simple epitope in HEG1, and the SKxPSxVS sequence within the epitope was essential for SKM9-2 recognition. Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900. Neuraminidase treatment analysis also confirmed that the epitope in mesothelioma cells contained a similar glycan modification. The specific detection of mesothelioma with SKM9-2 can thus be performed by the recognition of sialylated glycan modification in the specific region of HEG1.
CcpA Coordinates Growth/Damage Balance for Streptococcus pyogenes Pathogenesis
Authors: Paluscio Elyse , Watson Michael E. , Caparon Michael G. 
Published: September 2018

AbstractTo achieve maximum fitness, pathogens must balance growth with tissue damage, coordinating metabolism and virulence factor expression. In the gram-positive bacterium Streptococcus pyogenes, the DNA-binding transcriptional regulator Carbon Catabolite Protein A (CcpA) is a master regulator of both carbon catabolite repression and virulence, suggesting it coordinates growth/damage balance. To examine this, two murine models were used to compare the virulence of a mutant lacking CcpA with a mutant expressing CcpA locked into its high-affinity DNA-binding conformation (CcpAT307Y). In models of acute soft tissue infection and of long-term asymptomatic mucosal colonization, both CcpA mutants displayed altered virulence, albeit with distinct growth/damage profiles. Loss of CcpA resulted in a diminished ability to grow in tissue, leading to less damage and early clearance. In contrast, constitutive DNA-binding activity uncoupled the growth/damage relationship, such that high tissue burdens and extended time of carriage were achieved, despite reduced tissue damage. These data demonstrate that growth/damage balance can be actively controlled by the pathogen and implicate CcpA as a master regulator of this relationship. This suggests a model where the topology of the S. pyogenes virulence network has evolved to couple carbon source selection with growth/damage balance, which may differentially influence pathogenesis at distinct tissues.
Effect of transition metal alloying elements on the deformation of Ti-44Al-8Nb-0.2B-0.2Y alloys
Authors: Zhang Laiqi , Ge Gengwu , Lin Junpin , Aindow Mark , Zhang Lichun 
Published: September 2018

AbstractA series of β-γ Ti-44Al-8Nb-0.2B-0.2Y alloys have been modified with 0.5 to 2.0 at.% of the β-stabilizing elements Mn, Cr, Mo and V. Additions of Cr and Mo alone result in a decrease in the flow stress, whereas the opposite effect was observed for additions of V. For alloys with Mn additions, a minimum value of the flow stress was achieved in the alloy with 1.5% Mn. For alloys with combined additions, optimum hot deformation behavior was obtained for the alloy with 1.5% Mn and 1.0% Cr.
Nod2 Deficiency in mice is Associated with Microbiota Variation Favouring the Expansion of mucosal CD4+ LAP+ Regulatory Cells
Authors: Butera A. , Di Paola M. , Pavarini L. , Strati F. , Pindo M. , Sanchez M. , Cavalieri D. , Boirivant M. , De Filippo C. 
Published: September 2018

AbstractNucleotide-binding Oligomerization Domain-2 (NOD2) mutations are associated with an increased risk to develop Crohn’s Disease. In previous studies, we have shown that Nod2−/− mice manifest increased proportion of Lamina Propria (LP) CD4+ LAP+ Foxp3− regulatory cells, when compared with Nod2+/+ mice, while CD4+ Foxp3 + regulatory cells were not affected. Here, we investigated the Nod2 gut microbiota, by 16S rRNA pyrosequencing, at steady state and after TNBS-colitis induction in mice reared separately or in cohousing, correlating the microbial profiles with LP regulatory T cells proportion and tissue cytokines content. We found that enrichment of Rikenella and Alistipes (Rikenellaceae) in Nod2−/− mice at 8 weeks of age reared separately was associated with increased proportion of CD4+ LAP+ Foxp3− cells and less severe TNBS-colitis. In co-housed mice the acquisition of Rickenellaceae by Nod2+/+ mice was associated with increased CD4+ LAP+ Foxp3− proportion and less severe colitis. Severe colitis was associated with enrichment of gram-negative pathobionts (Escherichia and Enterococcus), while less severe colitis with protective bacteria (Barnesiella, Odoribacter and Clostridium IV). Environmental factors acting on genetic background with different outcomes according to their impact on microbiota, predispose in different ways to inflammation. These results open a new scenario for therapeutic attempt to re-establish eubiosis in Inflammatory Bowel Disease patients with NOD2 polymorphisms.
Enrichment of gut-derived Fusobacterium is associated with suboptimal immune recovery in HIV-infected individuals
Authors: Lee Soo Ching , Chua Ling Ling , Yap Siew Hwei , Khang Tsung Fei , Leng Chan Yoon , Raja Azwa Raja Iskandar , Lewin Sharon R. , Kamarulzaman Adeeba , Woo Yin Ling , Lim Yvonne Ai Lian , Loke P’ng , Rajasuriar Reena 
Published: September 2018

AbstractWe explored the gut microbiota profile among HIV-infected individuals with diverse immune recovery profiles following long-term suppressive ART and investigated the relationship between the altered bacteria with markers of immune dysfunction. The microbiota profile of rectal swabs from 26 HIV-infected individuals and 20 HIV-uninfected controls were examined. Patients were classified as suboptimal responders, sIR (n = 10, CD4 T-cell <350 cells/ul) and optimal responders, oIR (n = 16, CD4 T-cell >500 cells/ul) after a minimum of 2 years on suppressive ART. Canonical correlation analysis(CCA) and multiple regression modelling were used to explore the association between fecal bacterial taxa abundance and immunological profiles in optimal and suboptimal responders. We foundFusobacteriumwas significantly enriched among the HIV-infected and the sIR group. CCA results showed thatFusobacteriumabundance was negatively correlated with CD4 T-cell counts, but positively correlated with CD4 T-cell activation and CD4 Tregs. Multiple linear regression analysis adjusted for age, baseline CD4 T-cell count, antibiotic exposure and MSM status indicated that higherFusobacteriumrelative abundance was independently associated with poorer CD4 T-cell recovery following ART. Enrichment ofFusobacteriumwas associated with reduced immune recovery and persistent immune dysfunction following ART. Modulating the abundance of this bacterial taxa in the gut may be a viable intervention to improve immune reconstitution in our setting.
Sleep Disturbance and Related Factors in Patients with Nasopharyngeal Carcinoma and Their Family Caregivers Prior to the Initiation of Treatment
Authors: Lai Xiao-Ying , Tang Zhong-Min , Zhu Xiao-Dong , Li Ling , Qin Xue-Yan , Lan Jiang-Ling , Lu Chun-Ping , Lyu Zhi-Chan , Liang Li-Qiao , Chen Li-Jun 
Published: September 2018

AbstractSleep disturbance is a common complaint in cancer patients. However, less is known about the parameters of sleep in patients with nasopharyngeal cancer (NPC) and their family caregivers (FCs) when they are about to begin treatment. We investigated the sleep quality in patients with NPC and their FCs before treatment and determined the related factors that predict sleep disturbance in these patients before therapy. A total of 101 patient-FC dyads were recruited. They completed the Pittsburgh Sleep Quality Index (PSQI) prior to treatment. No differences were found in sleep disturbance between patients (38.6%) and their FCs (31.7%). Patients reported significantly higher rates of short sleep duration than their FCs (P = 0.011). Logistic regression analyses showed that older patients were more prone to suffer from poor sleep quality before treatment (OR = 1.06, 95% CI = 1.01–1.10, P = 0.008), while patients with a higher BMI were less likely to experience sleep disturbance (OR = 0.83, 95% CI = 0.71–0.96, P = 0.012). Sleep disturbance is a significant problem in patients with NPC and their FCs before therapy. Older patients and those with a lower BMI appear to be more inclined to suffer from poor sleep before treatment.
The evolution of fruit colour: phylogeny, abiotic factors and the role of mutualists
Authors: Valenta Kim , Kalbitzer Urs , Razafimandimby Diary , Omeja Patrick , Ayasse Manfred , Chapman Colin A. , Nevo Omer 
Published: September 2018

AbstractThe adaptive significance of fruit colour has been investigated for over a century. While colour can fulfil various functions, the most commonly tested hypothesis is that it has evolved to increase fruit visual conspicuousness and thus promote detection and consumption by seed dispersing animals. However, fruit colour is a complex trait which is subjected to various constraints and selection pressures. As a result, the effect of animal selection on fruit colour are often difficult to identify, and several studies have failed to detect it. Here, we employ an integrative approach to examine what drives variation in fruit colour. We quantified the colour of ripe fruit and mature leaves of 97 tropical plant species from three study sites in Madagascar and Uganda. We used phylogenetically controlled models to estimate the roles of phylogeny, abiotic factors, and dispersal mode on fruit colour variation. Our results show that, independent of phylogeny and leaf coloration, mammal dispersed fruits are greener than bird dispersed fruits, while the latter are redder than the former. In addition, fruit colour does not correlate with leaf colour in the visible spectrum, but fruit reflection in the ultraviolet area of the spectrum is strongly correlated with leaf reflectance, emphasizing the role of abiotic factors in determining fruit colour. These results demonstrate that fruit colour is affected by both animal sensory ecology and abiotic factors and highlight the importance of an integrative approach which controls for the relevant confounding factors.
Flexible Learning-Free Segmentation and Reconstruction of Neural Volumes
Authors: Shahbazi Ali , Kinnison Jeffery , Vescovi Rafael , Du Ming , Hill Robert , Joesch Maximilian , Takeno Marc , Zeng Hongkui , da Costa Nuno Maçarico , Grutzendler Jaime , Kasthuri Narayanan , Scheirer Walter J. 
Published: September 2018

AbstractImaging is a dominant strategy for data collection in neuroscience, yielding stacks of images that often scale to gigabytes of data for a single experiment. Machine learning algorithms from computer vision can serve as a pair of virtual eyes that tirelessly processes these images, automatically detecting and identifying microstructures. Unlike learning methods, our Flexible Learning-free Reconstruction of Imaged Neural volumes (FLoRIN) pipeline exploits structure-specific contextual clues and requires no training. This approach generalizes across different modalities, including serially-sectioned scanning electron microscopy (sSEM) of genetically labeled and contrast enhanced processes, spectral confocal reflectance (SCoRe) microscopy, and high-energy synchrotron X-ray microtomography (μCT) of large tissue volumes. We deploy the FLoRIN pipeline on newly published and novel mouse datasets, demonstrating the high biological fidelity of the pipeline’s reconstructions. FLoRIN reconstructions are of sufficient quality for preliminary biological study, for example examining the distribution and morphology of cells or extracting single axons from functional data. Compared to existing supervised learning methods, FLoRIN is one to two orders of magnitude faster and produces high-quality reconstructions that are tolerant to noise and artifacts, as is shown qualitatively and quantitatively.
Protecting quantum resources via frequency modulation of qubits in leaky cavities
Authors: Mortezapour Ali , Lo Franco Rosario 
Published: September 2018

AbstractFinding strategies to preserve quantum resources in open systems is nowadays a main requirement for reliable quantum-enhanced technologies. We address this issue by considering structured cavities embedding qubits driven by a control technique known as frequency modulation. We first study a single qubit in a lossy cavity to determine optimal modulation parameters and qubit-cavity coupling regime allowing a gain of four orders of magnitude concerning coherence lifetimes. We relate this behavior to the inhibition of the qubit effective decay rate rather than to stronger memory effects (non-Markovianity) of the system. We then exploit these findings in a system of noninteracting qubits embedded in separated cavities to gain basic information about scalability of the procedure. We show that the determined modulation parameters enable lifetimes of quantum resources, such as entanglement, discord and coherence, three orders of magnitude longer than their natural (uncontrolled) decay times. We discuss the feasibility of the system within the circuit-QED scenario, typically employed in the current quantum computer prototypes. These results provide new insights towards efficient experimental strategies against decoherence.
Visual salience of the stop signal affects the neuronal dynamics of controlled inhibition
Authors: Pani Pierpaolo , Giarrocco Franco , Giamundo Margherita , Montanari Roberto , Brunamonti Emiliano , Ferraina Stefano 
Published: September 2018

AbstractThe voluntary control of movement is often tested by using the countermanding, or stop-signal task that sporadically requires the suppression of a movement in response to an incoming stop-signal. Neurophysiological recordings in monkeys engaged in the countermanding task have shown that dorsal premotor cortex (PMd) is implicated in movement control. An open question is whether and how the perceptual demands inherent the stop-signal affects inhibitory performance and their underlying neuronal correlates. To this aim we recorded multi-unit activity (MUA) from the PMd of two male monkeys performing a countermanding task in which the salience of the stop-signals was modulated. Consistently to what has been observed in humans, we found that less salient stimuli worsened the inhibitory performance. At the neuronal level, these behavioral results were subtended by the following modulations: when the stop-signal was not noticeable compared to the salient condition the preparatory neuronal activity in PMd started to be affected later and with a less sharp dynamic. This neuronal pattern is probably the consequence of a less efficient inhibitory command useful to interrupt the neural dynamic that supports movement generation in PMd.
The Stochastic Transport Dynamics of a Conserved Quantity on a Complex Network
Authors: Medina Pablo , Clark Jaime , Kiwi Miguel , Torres Felipe , Rogan José , Valdivia Juan Alejandro 
Published: September 2018

AbstractThe stochastic dynamics of conserved quantities is an emergent phenomena observed in many complex systems, ranging from social and to biological networks. Using an extension of the Ehrenfest urn model on a complex network, over which a conserved quantity is transported in a random fashion, we study the dynamics of many elementary packets transported through the network by means of a master equation approach and compare with the mean field approximation and stochastic simulations. By use of the mean field theory, it is possible to compute an approximation to the ensemble average evolution of the number of packets in each node which, in the thermodynamic limit, agrees quite well with the results of the master equation. However, the master equation gives a more complete description of the stochastic system and provides a probabilistic view of the occupation number at each node. Of particular relevance is the standard deviation of the occupation number at each node, which is not uniform for a complex network. We analyze and compare different network topologies (small world, scale free, Erdos-Renyi, among others). Given the computational complexity of directly evaluating the asymptotic, or equilibrium, occupation number probability distribution, we propose a scaling relation with the number of packets in the network, that allows to construct the asymptotic probability distributions from the network with one packet. The approximation, which relies on the same matrix found in the mean field approach, becomes increasingly more accurate for a large number of packets.