bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calmodulin dissociates the STIM1-Orai1 complex and STIM1 oligomers
Authors: Li Xin , Wu Guangyan , Yang Yin , Fu Shijuan , Liu Xiaofen , Kang Huimin , Yang Xue , Su Xun-Cheng , Shen Yuequan 
Published: October 2017

AbstractStore-operated calcium entry (SOCE) is a major pathway for calcium ions influx into cells and has a critical role in various cell functions. Here we demonstrate that calcium-bound calmodulin (Ca2+-CaM) binds to the core region of activated STIM1. This interaction facilitates slow Ca2+-dependent inactivation after Orai1 channel activation by wild-type STIM1 or a constitutively active STIM1 mutant. We define the CaM-binding site in STIM1, which is adjacent to the STIM1–Orai1 coupling region. The binding of Ca2+-CaM to activated STIM1 disrupts the STIM1–Orai1 complex and also disassembles STIM1 oligomer. Based on these results we propose a model for the calcium-bound CaM-regulated deactivation of SOCE.
The giant protein titin regulates the length of the striated muscle thick filament
Authors: Tonino Paola , Kiss Balazs , Strom Josh , Methawasin Mei , Smith John E. , Kolb Justin , Labeit Siegfried , Granzier Henk 
Published: October 2017

AbstractThe contractile machinery of heart and skeletal muscles has as an essential component the thick filament, comprised of the molecular motor myosin. The thick filament is of a precisely controlled length, defining thereby the force level that muscles generate and how this force varies with muscle length. It has been speculated that the mechanism by which thick filament length is controlled involves the giant protein titin, but no conclusive support for this hypothesis exists. Here we show that in a mouse model in which we deleted two of titin’s C-zone super-repeats, thick filament length is reduced in cardiac and skeletal muscles. In addition, functional studies reveal reduced force generation and a dilated cardiomyopathy (DCM) phenotype. Thus, regulation of thick filament length depends on titin and is critical for maintaining muscle health.
An integrative method to decode regulatory logics in gene transcription
Authors: Yan Bin , Guan Daogang , Wang Chao , Wang Junwen , He Bing , Qin Jing , Boheler Kenneth R. , Lu Aiping , Zhang Ge , Zhu Hailong 
Published: October 2017

AbstractModeling of transcriptional regulatory networks (TRNs) has been increasingly used to dissect the nature of gene regulation. Inference of regulatory relationships among transcription factors (TFs) and genes, especially among multiple TFs, is still challenging. In this study, we introduced an integrative method, LogicTRN, to decode TF–TF interactions that form TF logics in regulating target genes. By combiningcis-regulatory logics and transcriptional kinetics into one single model framework, LogicTRN can naturally integrate dynamic gene expression data and TF-DNA-binding signals in order to identify the TF logics and to reconstruct the underlying TRNs. We evaluated the newly developed methodology using simulation, comparison and application studies, and the results not only show their consistence with existing knowledge, but also demonstrate its ability to accurately reconstruct TRNs in biological complex systems.
Staphylococcus aureus interaction with Pseudomonas aeruginosa biofilm enhances tobramycin resistance
Authors: Beaudoin T. , Yau Y. C. W. , Stapleton P. J. , Gong Y. , Wang P. W. , Guttman D. S. , Waters V. 
Published: October 2017

AbstractAntimicrobial resistance is a significant threat to the treatment of infectious disease. Multiple mechanisms of resistance to different classes of antibiotics have been identified and well-studied. However, these mechanisms are studied with bacteria in isolation, whereas often, infections have a polymicrobial basis. Using a biofilm slide chamber model, we visualized the formation and development of clinical Pseudomonas aeruginosa biofilms in the presence of secreted Staphylococcus aureus exoproducts, two bacteria that commonly co-infect pediatric patients with cystic fibrosis. We showed that, over time, certain isolates of P. aeruginosa can form different biofilm architecture in the presence of S. aureus exoproducts. We further determined that this interaction was dependent on Psl produced by P. aeruginosa and staphylococcal protein A from S. aureus. Importantly, we identified a mechanism of antibiotic resistance to tobramycin that is dependent on the polymicrobial interactions between these two bacteria. This interaction occurred in isolates of P. aeruginosa recovered from children with cystic fibrosis who failed to clear P. aeruginosa following inhaled tobramycin treatment.
Myosin X is recruited to nascent focal adhesions at the leading edge and induces multi-cycle filopodial elongation
Authors: He Kangmin , Sakai Tsuyoshi , Tsukasaki Yoshikazu , Watanabe Tomonobu M. , Ikebe Mitsuo 
Published: October 2017

AbstractFilopodia protrude from the leading edge of cells and play important roles in cell motility. Here we report the mechanism of myosin X (encoded by Myo10)-induced multi-cycle filopodia extension. We found that actin, Arp2/3, vinculin and integrin-β first accumulated at the cell’s leading edge. Myosin X was then gathered at these sites, gradually clustered by lateral movement, and subsequently initiated filopodia formation. During filopodia extension, we found the translocation of Arp2/3 and integrin-β along filopodia. Arp2/3 and integrin-β then became localized at the tip of filopodia, from where myosin X initiated the second extension of filopodia with a change in extension direction, thus producing long filopodia. Elimination of integrin-β, Arp2/3 and vinculin by siRNA significantly attenuated the myosin-X-induced long filopodia formation. We propose the following mechanism. Myosin X accumulates at nascent focal adhesions at the cell’s leading edge, where myosin X promotes actin convergence to create the base of filopodia. Then myosin X moves to the filopodia tip and attracts integrin-β and Arp2/3 for further actin nucleation. The tip-located myosin X then initiates the second cycle of filopodia elongation to produce the long filopodia.
Effect of Specific Mutations in Cd300 Complexes Formation; Potential Implication of Cd300f in Multiple Sclerosis
Authors: Martínez-Barriocanal Águeda , Arcas-García Andrea , Magallon-Lorenz Miriam , Ejarque-Ortíz Aroa , Negro-Demontel María Luciana , Comas-Casellas Emma , Schwartz Simo , Malhotra Sunny , Montalban Xavier , Peluffo Hugo , Martín Margarita , Comabella Manuel , Sayós Joan 
Published: October 2017

AbstractHerein, we have used bioinformatics tools to predict five clusters defining ligand-binding sites on the extracellular domain of human CD300b receptor, presumably involved in the formation of both homodimers and heterodimers with other CD300 family members. Site-directed mutagenesis revealed residues glutamic acid 28 and glutamine 29 in cluster 5 to be necessary for the formation of CD300b complexes. Surprisingly, the disruption of cluster 2 and 4 reconstituted the binding capability lost by the mutation of residues glutamic acid 28 to alanine, glutamine 29 to alanine (E28A-Q29G). We identified a missense mutation arginine 33 to glutamine (R33Q) in CD300f by direct sequencing of exon 2 in peripheral blood samples from 50 patients with multiple sclerosis (MS). Levels of expression of CD300f were almost undetectable on monocytes from the patient bearing the R33Q mutation compared with healthy individuals. Whereas R33Q mutation had no effect in the formation of CD300f complexes, the inhibition of protein synthesis with cycloheximide indicated that CD300f R33Q is less stable than native CD300f. Finally, we report that the levels of expression of CD300f on the surface of classical and intermediate monocytes from MS patients are significantly lower when compared to the same cell populations in healthy individuals.
Racial disparities in patient survival and tumor mutation burden, and the association between tumor mutation burden and cancer incidence rate
Authors: Zhang Wensheng , Edwards Andrea , Flemington Erik K. , Zhang Kun 
Published: October 2017

AbstractThe causes underlying racial disparities in cancer are multifactorial. In addition to socioeconomic issues, biological factors may contribute to these inequities, especially in disease incidence and patient survival. To date, there have been few studies that relate the disparities in these aspects to genetic aberrations. In this work, we studied the impacts of race on the patient survival and tumor mutation burden using the data released by the Cancer Genome Atlas (TCGA). The potential relationship between mutation burden and disease incidence is further inferred by an integrative analysis of TCGA data and the data from the Surveillance, Epidemiology, and End Results (SEER) Program. The results show that disparities are present (p < 0.05) in patient survival of five cancers, such as head and neck squamous cell carcinoma. The numbers of tumor driver mutations are differentiated (p < 0.05) over the racial groups in five cancers, such as lung adenocarcinoma. By treating a specific cancer type and a racial group as an “experimental unit”, driver mutation numbers demonstrate a significant (r = 0.46, p < 0.002) positive correlation with cancer incidence rates, especially when the five cancers with mutational disparities are exclusively focused (r = 0.88, p < 0.00002). These results enrich our understanding of racial disparities in cancer and carcinogenic process.
A new description of epileptic seizures based on dynamic analysis of a thalamocortical model
Authors: Sohanian Haghighi H. , Markazi A. H. D. 
Published: October 2017

AbstractIncreasing evidence suggests that the brain dynamics can be interpreted from the viewpoint of nonlinear dynamical systems. The aim of this paper is to investigate the behavior of a thalamocortical model from this perspective. The model includes both cortical and sensory inputs that can affect the dynamic nature of the model. Driving response of the model subjected to various harmonic stimulations is considered to identify the effects of stimulus parameters on the cortical output. Detailed numerical studies including phase portraits, Poincare maps and bifurcation diagrams reveal a wide range of complex dynamics including period doubling and chaos in the output. Transition between different states can occur as the stimulation parameters are changed. In addition, the amplitude jump phenomena and hysteresis are shown to be possible as a result of the bending in the frequency response curve. These results suggest that the jump phenomenon due to the brain nonlinear resonance can be responsible for the transitions between ictal and interictal states.
Blue carbon stores in tropical seagrass meadows maintained under green turtle grazing
Authors: Johnson Robert A. , Gulick Alexandra G. , Bolten Alan B. , Bjorndal Karen A. 
Published: October 2017

AbstractSeagrass meadows are important sites for carbon storage. Green turtles (Chelonia mydas) are marine megaherbivores that consume seagrass throughout much of their global range. With successful conservation efforts, turtle abundance will increase, leading to more meadows being returned to their natural grazed state. There is concern this may lead to a loss of carbon stored in these systems, but the effects of green turtle grazing on seagrass ecosystem carbon dynamics have not been investigated. Here we experimentally show that despite 79% lower net ecosystem production (NEP) following grazing (24.7 vs. 119.5 mmol C m−2 d−1) in a Caribbean Thalassia testudinum seagrass meadow, grazed areas maintained net positive metabolic carbon uptake. Additionally, grazing did not change the meadow production to respiration ratio, indicating it did not stimulate remineralization of sediment carbon stores. Compared to other published estimates of seagrass NEP (median: 20.6 mmol C m−2 d−1), NEP in grazed Caribbean T. testudinum meadows is similar to that in many other ungrazed systems. Our results demonstrate that while grazing does decrease potential future carbon sequestration as a result of lower NEP, it does not promote a metabolic release of current carbon stocks.
De novo mutations of TUBA3D are associated with keratoconus
Authors: Hao Xiao-dan , Chen Peng , Zhang Yang-yang , Li Su-xia , Shi Wei-yun , Gao Hua 
Published: October 2017

AbstractKeratoconus (KC) is a common degenerative corneal disease, and heredity plays a key role in its development. Although few genes are known to cause KC, a large proportion of disease-causing genes remain to be revealed. Here, we report the identification of TUBA3D as a novel gene linked to KC. Using whole-exome sequencing of a twins pedigree, a novel de novo mutation (c.31 C > T, p.Gln11stop) in TUBA3D gene was identified. A screening performed in 200 additional unrelated patients with KC revealed another two mutations (c.201insTT, p.Val68Leufs*2; c.*2 G > A) in two patients. TUBA3D was expressed highly in the cornea, and the twins had lower TUBA3D expression and higher UPA and MMP1 expressions than the normal parents. Through function prediction and in vitro cell experiment, we further demonstrated that the mutant proteins of TUBA3D were unstable and could lead to human corneal fibroblast cells performing higher MMPs expression and oxidative stress. These changes thus reduce the amount of extracellular matrices within corneas and undoubtedly play a major role in stromal thinning, which is characteristic of KC corneas. Our study showed that TUBA3D is a new gene that causes KC, thus supporting the evidence that this protein has an additional function into the human cornea.
Stromal striae: a new insight into corneal physiology and mechanics
Authors: Grieve Kate , Ghoubay Djida , Georgeon Cristina , Latour Gael , Nahas Amir , Plamann Karsten , Crotti Caroline , Bocheux Romain , Borderie Marie , Nguyen Thu-Mai , Andreiuolo Felipe , Schanne-Klein Marie-Claire , Borderie Vincent 
Published: October 2017

AbstractWe uncover the significance of a previously unappreciated structural feature in corneal stroma, important to its biomechanics. Vogt striae are a known clinical indicator of keratoconus, and consist of dark, vertical lines crossing the corneal depth. However we detected stromal striae in most corneas, not only keratoconus. We observed striae with multiple imaging modalities in 82% of 118 human corneas, with pathology-specific differences. Striae generally depart from anchor points at Descemet’s membrane in the posterior stroma obliquely in a V-shape, whereas in keratoconus, striae depart vertically from posterior toward anterior stroma. Optical coherence tomography shear wave elastography showed discontinuity of rigidity, and second harmonic generation and scanning electron microscopies showed undulation of lamellae at striae locations. Striae visibility decreased beyond physiological pressure and increased beyond physiological hydration. Immunohistology revealed striae to predominantly contain collagen VI, lumican and keratocan. The role of these regions of collagen VI linking sets of lamellae may be to absorb increases in intraocular pressure and external shocks.
Exceptional 20th century glaciological regime of a major SE Greenland outlet glacier
Authors: Andresen Camilla S. , Kokfelt Ulla , Sicre Marie-Alexandrine , Knudsen Mads Faurschou , Dyke Laurence M. , Klein Vincent , Kaczmar Fanny , Miles Martin W. , Wangner David 
Published: October 2017

AbstractThe early 2000s accelerated ice-mass loss from large outlet glaciers in W and SE Greenland has been linked to warming of the subpolar North Atlantic. To investigate the uniqueness of this event, we extend the record of glacier and ocean changes back 1700 years by analyzing a sediment core from Sermilik Fjord near Helheim Glacier in SE Greenland. We show that multidecadal to centennial increases in alkenone-inferred Atlantic Water SSTs on the shelf occurred at times of reduced solar activity during the Little Ice Age, when the subpolar gyre weakened and shifted westward promoted by atmospheric blocking events. Helheim Glacier responded to many of these episodes with increased calving, but despite earlier multidecadal warming episodes matching the 20th century high SSTs in magnitude, the glacier behaved differently during the 20th century. We suggest the presence of a floating ice tongue since at least 300 AD lasting until 1900 AD followed by elevated 20th century glacier calving due to the loss of the tongue. We attribute this regime shift to 20th century unprecedented low sea-ice occurrence in the East Greenland Current and conclude that properties of this current are important for the stability of the present ice tongues in NE Greenland.
Dynamics of the stochastic chemostat with Monod-Haldane response function
Authors: Wang Liang , Jiang Daqing , Wolkowicz Gail S. K. , O’Regan Donal 
Published: October 2017

AbstractThe stochastic chemostat model with Monod-Haldane response function is perturbed by environmental white noise. This model has a global positive solution. We demonstrate that there is a stationary distribution of the stochastic model and the system is ergodic under appropriate conditions, on the basis of Khasminskii’s theory on ergodicity. Sufficient criteria for extinction of the microbial population in the stochastic system are established. These conditions depend strongly on the Brownian motion. We find that even small scale white noise can promote the survival of microorganism populations, while large scale noise can lead to extinction. Numerical simulations are carried out to illustrate our theoretical results.
Mapping the expression of the sex determining factor Doublesex1 in Daphnia magna using a knock-in reporter
Authors: Nong Quang Dang , Mohamad Ishak Nur Syafiqah , Matsuura Tomoaki , Kato Yasuhiko , Watanabe Hajime 
Published: October 2017

AbstractSexually dimorphic traits are common and widespread among animals. The expression of the Doublesex-/Mab-3-domain (DM-domain) gene family has been widely studied in model organisms and has been proven to be essential for the development and maintenance of sex-specific traits. However, little is known about the detailed expression patterns in non-model organisms. In the present study, we demonstrated the spatiotemporal expression of the DM-domain gene, doublesex1 (dsx1), in the crustacean Daphnia magna, which parthenogenetically produces males in response to environmental cues. We developed a dsx1 reporter strain to track dsx1 activity in vivo by inserting the mCherry gene into the dsx1 locus using the TALEN-mediated knock-in approach. After confirming dsx1 expression in male-specific traits in juveniles and adults, we performed time-lapse imaging of embryogenesis. Shortly after gastrulation stage, a presumptive primary organiser, named cumulus, first showed male-specific dsx1 expression. This cell mass moved to the posterior growth zone that distributes dsx1-expressing progenitor cells across the body during axial elongation, before embryos start male-specific dsx1 expression in sexually dimorphic structures. The present study demonstrated the sex-specific dsx1 expression in cell populations involved in basal body formation.
Identification of differentially expressed circular RNAs in human monocyte derived macrophages response to Mycobacterium tuberculosis infection
Authors: Huang Zikun , Su Rigu , Deng Zhen , Xu Jianqing , Peng Yiping , Luo Qing , Li Junming 
Published: October 2017

AbstractMacrophages act as the first line of host immune defense against Mycobacterium tuberculosis (Mtb). Recent studies have demonstrated circular RNAs (circRNAs) are implicated in a variety of physiological and pathological processes; however, the role of circRNAs in macrophages response to Mtb infection remain unknown. To address this issue, here we characterized circRNAs expression profiles in human monocyte derived macrophages (MDMs) response to Mtb infection using microarray assay. Our results revealed that many circRNAs were differentially expressed in human MDMs after Mtb infection; of these, 32 circRNAs were up-regulated and 110 were down-regulated. Real time PCR results were generally consistent with the microarray data. Furthermore, we found that hsa_circ_0043497 and hsa_circ_0001204 may be effective diagnostic biomarkers for TB. This study provides the first evidence that circRNAs alterations are involved in human MDMs response to TB infection and reveal potential targets for diagnostics and the treatment of TB.
Characterization of old RHDV strains by complete genome sequencing identifies a novel genetic group
Authors: Lopes Ana M. , Silvério Diogo , Magalhães Maria J. , Areal Helena , Alves Paulo C. , Esteves Pedro J. , Abrantes Joana 
Published: October 2017

AbstractRabbit hemorrhagic disease (RHD) is a veterinary disease that affects the European rabbit and has a significant economic and ecological negative impact. In Portugal, rabbit hemorrhagic disease virus (RHDV) was reported in 1989 and still causes enzootic outbreaks. Several recombination events have been detected in RHDV strains, including in the first reported outbreak. Here we describe the occurrence of recombination in RHDV strains recovered from rabbit and Iberian hare samples collected in the mid-1990s in Portugal. Characterization of full genomic sequences revealed the existence of a single recombination breakpoint at the boundary of the non-structural and the structural encoding regions, further supporting the importance of this region as a recombination hotspot in lagoviruses. Phylogenetic analysis showed that in the structural region, the recombinant strains were similar to pathogenic G1 strains, but in the non-structural region they formed a new group that diverged ~13% from known strains. No further reports of such group exist, but this recombination event was also detected in an Iberian hare that was associated with the earliest species jump in RHDV. Our results highlight the importance of the characterization of full genomes to disclose RHDV evolution and show that lagoviruses’ diversity has been significantly undersampled.
Energetic mitochondrial failing in vitiligo and possible rescue by cardiolipin
Authors: Dell’Anna Maria Lucia , Ottaviani Monica , Kovacs Daniela , Mirabilii Simone , Brown David A. , Cota Carlo , Migliano Emilia , Bastonini Emanuela , Bellei Barbara , Cardinali Giorgia , Ricciardi Maria Rosaria , Tafuri Agostino , Picardo Mauro 
Published: October 2017

AbstractVitiligo is characterized by death or functional defects of epidermal melanocytes through still controversial pathogenic process. Previously, we showed that mitochondria-driven pre-senescent phenotype diminishes the capability of vitiligo melanocytes to cope with stressful stimuli. In the current study, we investigated markers of mitochondrial energy metabolism including the PGC1a axis, and then we determined the index of mitochondrial impairment using a cytomic approach. We found in cultured epidermal vitiligo melanocytes, compared to healthy ones, low ATP, increased proton leakage, and altered expression of several glycolytic enzymes (hexokinase II, pyruvic dehydrogenase kinase 1 and pyruvic kinase M2), We suggest that the low ATP production may be sufficient in steady-state conditions but it is unable to cover further needs. We also found in vitiligo melanocyrtes hyper-activation of the PGC1α axis, finalized to counteract the energy defect. Cytomic analysis, supported by MitoTracker Red pattern and ex-vivo immunohistochemistry, suggested an increased mitochondrial mass, possibly useful to ensure the essential ATP level. Finally, pharmacological cardiolipin stabilization reverted the energetic impairment, confirming the initial mitochondrial role. In conclusion, we report new insight in the pathogenetic mechanism of viitligo and indicate that the mitochondrial failure rescue by cardiolipin manipulation may be a new intriguing target in treatment development.