bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-omic profiling of tyrosine kinase inhibitor-resistant K562 cells suggests metabolic reprogramming to promote cell survival
Authors: Noel Brett M. , Ouellette Steven B. , Marholz Laura , Dickey Deborah , Navis Connor , Yang Tzu-Yi , Nguyen Vinh , Parker Sarah J. , Bernlohr David , Sachs Zohar , Parker Laurie L. 
Published: May 2018

AbstractResistance to chemotherapy can occur through a wide variety of mechanisms. Resistance to tyrosine kinase inhibitors (TKIs) often arises from kinase mutations-however, “off-target” resistance occurs but is poorly understood. Previously, we established cell line resistance models for three TKIs used in chronic myeloid leukemia treatment, and found that resistance was not attributed entirely to failure of kinase inhibition. Here, we performed global, integrated proteomic and transcriptomic profiling of these cell lines to describe mechanisms of resistance at the protein and gene expression level. We used whole transcriptome sequencing and SWATH-based data-independent acquisition mass spectrometry (DIA-MS), which does not require isotopic labels and provides quantitative measurements of proteins in a comprehensive, unbiased fashion. The proteomic and transcriptional data were correlated to generate an integrated understanding of the gene expression and protein alterations associated with TKI resistance. We defined mechanisms of resistance and two novel markers, CA1 and alpha-synuclein, that were common to all TKIs tested. Resistance to all of the TKIs was associated with oxidative stress responses, hypoxia signatures, and apparent metabolic reprogramming of the cells. Metabolite profiling and glucose-dependence experiments showed that resistant cells had routed their metabolism through glycolysis (particularly through the pentose phosphate pathway) and exhibited disruptions in mitochondrial metabolism. These experiments are the first to report a global, integrated proteomic, transcriptomic and metabolic analysis of TKI resistance. These data suggest that although the mechanisms are complex, targeting metabolic pathways along with TKI treatment may overcome pan-TKI resistance.Key Points:Alterations to metabolism are a common feature of target-mutation-independent resistance in CML cells across multiple clinically relevant TKIs.Carbonic anhydrase 1 (CA1) and a-synuclein (SNCA) are novel markers of metabolic reprogramming in TKI resistant CML cells.
The effect of dream report collection and dream incorporation on memory consolidation during sleep
Authors: Schoch Sarah F. , Cordi Maren J. , Schredl Michael , Rasch Bjöern 
Published: May 2018

AbstractWaking up during the night to collect dream reports is a commonly used method to study dreams. This method has also been applied in studies on the relationship between dreams and memory consolidation. However, it is unclear if these awakenings influence ongoing memory consolidation processes. Furthermore, only few studies have examined if task incorporation into dreams is related to enhanced performance in the task. Here we compare memory performance in a word-picture association learning task after a night with (up to six awakenings) and without awakenings in 22 young and healthy participants. We then examine if the task is successfully incorporated into the dreams and if this incorporation is related to the task performance the next morning. We show that while the awakenings impair both subjective and objective sleep quality, these awakenings did not impair ongoing memory consolidation during sleep. When dreams were collected during the night by awakenings, memories of the learning task were successfully incorporated into dreams. No incorporation occurred in dreams collected only in the morning. Task incorporation into NREM sleep dreams, but not REM sleep dreams showed a relationship with task performance the next morning.We conclude that the method of awakenings to collect dream reports is suitable for dream and memory studies, and is even crucial to uncover task incorporations. Furthermore, our study suggests that dreams in NREM rather than REM sleep might be related to processes of memory consolidation during sleep.
Cis-nonProline Peptides: Genuine Occurrences and their Functional Roles
Authors: Richardson Jane S. , Videau Lizbeth L. , Williams Christopher J. , Hintze Bradley J. , Lewis Steven M. , Richardson David C. 
Published: May 2018

AbstractWhilecispeptides preceding proline can occur about 5% of the time,cispeptides preceding any other residue (“cis-nonPro” peptides) are an extremely rare feature in protein structures, of considerable importance for two opposite reasons. On one hand, their genuine occurrences are mostly found at sites critical to biological function, from the active sites of carbohydrate enzymes to rare adjacent-residue disulfide bonds. On the other hand, acis-nonPro can easily be misfit into weak or ambiguous electron density, which led to a high incidence of unjustifiedcis-nonPro over the 2006-2015 decade. This paper uses high-resolution crystallographic data and especially stringent quality-filtering at the residue level to identify genuine occurrences ofcis-nonPro, and to survey both individual examples and broad patterns of their functionality.We explain the procedure developed to identify genuinecis-nonPro examples with almost no false positives. We then survey a large sample of the varied functional roles and structural contexts ofcis-nonPro, including the uses of specific amino acids for particular purposes. We emphasize aspects not previously covered: thatcis-nonPro always (except for vicinal disulfides) occur in highly ordered structure, and especially the great concentration of occurrence in proteins that process or bind carbohydrates (identified by occurrence on the CAZy website).
New interfaces on MiD51 for Drp1 recruitment and regulation
Authors: Ma Jun , Zhai Yujia , Chen Ming , Zhang Kai , Chen Quan , Pang Xiaoyun , Sun Fei 
Published: May 2018

ABSTRACTMitochondrial fission is facilitated by dynamin-related protein Drp1 and a variety of its receptors. However, the molecular mechanism of how Drp1 is recruited to the mitochondrial surface by receptors MiD49 and MiD51 remains elusive. Here, we showed that the interaction between Drp1 and MiD51 is regulated by GTP binding and depends on the polymerization of Drp1. We identified two regions on MiD51 that directly bind to Drp1, and found that dimerization of MiD51 via an intermolecular disulfide bond between C452 residues is required for MiD51 to directly interact with Drp1. Our Results have suggested a multi-faceted regulatory mechanism for the interaction between Drp1 and MiD51 that illustrates the potentially complicated and tight regulation of mitochondrial fission.
Combined effect of matrix quality and spatial heterogeneity on biodiversity decline
Authors: Ramos Irene , González González Cecilia , Urrutia Ana L. , Mora Van Cauwelaert Emilio , Benítez Mariana 
Published: May 2018

ABSTRACTThe land-sparing/land-sharing debate remains an oversimplified framework to evaluate landscape management strategies that aim to reconcile food production and biodiversity conservation. Still, biodiversity-yield curves, on which the framework has relied, provide valuable qualitative information on biodiversity’s sensitivity to agricultural practices, and much research has studied this relationship. But the potential effect of landscape configuration on biodiversity’s response to intensification has rarely been considered; besides, studies have often taken yield as an indicator of agricultural management and have generalized conclusions from studying particular taxonomic groups. In this work we adapt a metacommunity model to analyze factors that shape biodiversity’s response to agricultural intensification while addressing some of the simplifications of the land-sparing/land-sharing dichotomy. In particular, we study species richness decline in landscapes encompassing a combined gradient in matrix quality and configurational heterogeneity of habitat patches, and considering community dynamics. We found that species richness along an intensification gradient shifts from following a robust response to presenting an abrupt decline, as landscape heterogeneity increases, as stricter survival thresholds are applied to species or as habitat area is reduced. Our work highlights the interdependent effects of heterogeneity, habitat availability and matrix quality on biodiversity and contributes to a nuanced understanding of ecological and landscape factors that enable a robust response of biodiversity in the face of spatiotemporal perturbations.
4-hydroxyphenylpyruvate dioxygenase thermolability is responsible for temperature-dependent melanogenesis inAeromonas salmonicidasubsp.salmonicida
Authors: Qiao Yunqian , Wang Jiao , Wang He , Chai Baozhong , Rao Chufeng , Chen Xiangdong , Du Shishen 
Published: May 2018

AbstractAeromonas salmonicidasubsp.salmonicida(A.s.s) is a major pathogen affecting fisheries worldwide. It is a well-known member of the pigmentedAeromonasspecies, which produces melanin at ≤ 22 °C. However, melanogenesis decreases as the culture temperature increases and is completely suppressed at 30-35 °C while bacterial growth is not affected. The mechanism and biological significance of this temperature-dependent melanogenesis are not clear. Heterologous expression of anA.s.s.4-hydroxyphenylpyruvate dioxygenase (HppD), the most crucial enzyme in the HGA-melanin synthesis pathway, results in thermosensitive pigmentation inEscherichia coli, suggesting that HppD plays a key role in this process. In the current study, we demonstrated that the extreme thermolability of HppD is responsible for the temperature-dependent melanization ofA.s.s.Substitutions in three residues, Ser18, Pro103, or Leu119 of HppD fromA.s.sincreases the thermolability of this enzyme and results in temperature-independent melanogenesis. Moreover, replacing the corresponding residues of HppD fromAeromonasmedia strain WS, which forms pigment independent of temperature, with those ofA.s.sHppD leads to thermosensitive melanogenesis. Structural analysis suggested that mutations at these sites, especially at position P103, can strengthen the secondary structure of HppD and greatly improve its thermal stability. In addition, we found that HppD sequences of allA.s.sisolates are identical and that two of the three residues are completely conserved withinA.s.sisolates, which clearly distinguishes these from otherAeromonasstrains. We suggest that this property represents an adaptive strategy to the psychrophilic lifestyle ofA.s.s.ImportanceAeromonas salmonicidasubsp.salmonicida(A.s.s) is the causative agent of furunculosis, a bacterial septicemia of cold water fish of theSalmonidaefamily. As it has a well-defined host range,A.s.shas become an ideal model to investigate the co-evolution of host and pathogen. For many pathogens, melanin production is associated with virulence. Although other species ofAeromonascan produce melanin,A.s.sis the only member of this genus that has been reported to exhibit temperature-dependent melanization. Here we demonstrate that thermosensitive melanogenesis inA.s.sstrains is due to the thermolability of 4-hydroxyphenylpyruvate dioxygenase (HppD). The strictly conservedhppDsequences amongA.s.sand the exclusive thermosensitive pigmentation of these strains might provide insight into the role of melanin in the adaptation to a particular host, and offer a novel molecular marker to readily differentiateA.s.sstrains from otherA. salmonicidasubspecies andAeromonasspecies.
Radiopotentiation of Enzalutamide Over Human Prostate Cancer Cells as Assessed by Real-Time Cell Monitoring
Authors: Barrado Marta , Blanco-Luquin Idoia , Paola Andrea Navarrete , Visus Ignacio , Guerrero-Setas David , Escors David , Kochan Grazyna , Arias Fernando 
Published: May 2018

ABSTRACTWhile radiotherapy is the first line of treatment for prostate cancer, androgen blockade therapies are demonstrating significant survival benefit as monotherapies. As androgen blockade can cause cell death by apoptosis, it is likely that androgen blockade will potentiate the cytotoxic activities of radiotherapy. Here we tested the potential synergistic effects of these two treatments over two human metastatic prostate cancer cells by real time growth monitoring (RTCA), androgen-sensitive LNCaP cells and androgen-resistant PC-3. Both cell lines were highly resistant to high doses of radiotherapy. A pre-treatment of LNCaP cells with IC50 concentrations of enzalutamide significantly sensitized them to radiotherapy through enhanced apoptosis. In contrast, enzalutamide resistant PC-3 cells were not sensitized to radiotherapy by androgen blockade. These results provide evidence that the enzalutamide/radiotherapy combination could maximize therapeutic responses in patients with enzalutamide-sensitive prostate cancer.
Mechanisms of Kinesin-1 activation by Ensconsin/MAP7in vivo
Authors: Métivier Mathieu , Monroy Brigette Y. , Gallaud Emmanuel , Caous Renaud , Pascal Aude , Richard-Parpaillon Laurent , Guichet Antoine , Ori-McKenney Kassandra M. , Giet Régis 
Published: May 2018

AbstractCentrosome separation inDrosophilalarval neuroblasts and asymmetric transport of embryonic determinants in oocytes are both microtubule-dependent processes that require Kinesin-1 activation by Ensconsin/microtubule-associated protein 7 (MAP7). However, the molecular mechanism used by Ensconsin to activate Kinesin-1 remains elusive. Ensconsin/ MAP7 contains an N-terminal microtubule-binding domain (MBD) and a C-terminal Kinesin-binding domain (KBD). Using rescue experiments in live flies, we show that KBD expression alone is sufficient to fully rescue Ensconsin-dependent centrosome separation defects, but not the fast oocyte streaming and the localization patterns of Staufen and Gurken proteins. Interestingly, we show here for the first time that KBD binds and stimulates Kinesin-1 binding to Mtsin vivoandin vitro. We propose that the KBD/Kinesin-1 motor represents a minimal activation module that stimulates Kinesin-1 binding to Mts. Addition of the MBD, present in the full length Ensconsin allows this activation to occur directly on the Mt. Our data also suggest that in a very large cell with a complex microtubule network, but not in smaller cells, this dual activation by Ensconsin is essential for optimal Kinesin-1 targeting to the microtubule cytoskeleton.
Sedimentation and soil carbon accumulation in degraded mangrove forests of North Sumatra, Indonesia
Authors: Murdiyarso Daniel , Hanggara Bayu Budi , Lubis Ali Arman 
Published: May 2018

AbstractMangrove ecosystems are often referred to as “land builders” because of their ability to trap sediments transported from the uplands as well as from the oceans. The sedimentation process in mangrove areas is influenced by hydro-geomorphic settings that represent the tidal range and coastal geological formation. We estimated the sedimentation rate in North Sumatran mangrove forests using the210Pb radionuclide technique, also known as the constant rate supply method, and found that mudflats, fringes, and interior mangroves accreted 4.3 ± 0.2 mm yr−1, 5.6 ± 0.3 mm yr1, and 3.7 ± 0.2 mm yr−1, respectively. Depending on the subsurface changes, these rates could potentially keep pace with global sea level rise of 2.6−3.2 mm yr−1, except the interior mangrove they would also be able to cope with regional sea-level rise of 4.2 ± 0.4 mm yr−1. The mean soil carbon accumulation rates in the mudflats, fringes, and interior areas were 40.1 ± 6.9 g C m−2yr−1, 50.1 ± 8.8 g C m−2yr−1, and 47.7 ± 12.5 g C m−2yr−1, respectively, much lower than the published global average of 226 ± 39 g C m−2yr−1. We also found that based on the excess of radioactive elements derived from atomic bomb fallout, the sediment in the mudflat area was deposited since over 28 years ago, and is much younger than the sediment deposited in the interior and fringe areas that are 43 years 54 years old, respectively.
Cohesin interacts with a panoply of splicing factors required for cell cycle progression and genomic organization
Authors: Kim Jung-Sik , He Xiaoyuan , Liu Jie , Duan Zhijun , Kim Taeyeon , Gerard Julia , Kim Brian , Lane William S. , Noble William S. , Budnik Bogdan , Waldman Todd 
Published: May 2018

AbstractThe cohesin complex regulates sister chromatid cohesion, chromosome organization, gene expression, and DNA repair. Here we report that endogenous human cohesin interacts with a panoply of splicing factors and RNA binding proteins, including diverse components of the U4/U6.U5 tri-snRNP complex and several splicing factors that are commonly mutated in cancer. The interactions are enhanced during mitosis, and the interacting splicing factors and RNA binding proteins follow the cohesin cycle and prophase pathway of regulated interactions with chromatin. Depletion of cohesin-interacting splicing factors results in stereotyped cell cycle arrests and alterations in genomic organization. These data support the hypothesis that splicing factors and RNA binding proteins control cell cycle progression and genomic organization via regulated interactions with cohesin and chromatin.One Sentence SummaryEndogenous tagging reveals that cohesin interacts with diverse chromatin-bound splicing factors that regulate cell cycle progression and genomic organization in human cells.
The RhoGAP myosin 9/HUM-7 integrates membrane signals to modulate Rho/RHO-1 during embryonic morphogenesis inC. elegans
Authors: Wallace Andre G. , Raduwan Hamidah , Carlet John , Soto Martha C. 
Published: May 2018

AbstractDuring embryonic morphogenesis, cells and tissues undergo dramatic movements under the control of F-actin regulators. Our studies of epidermal cell migrations in developingC. elegansembryos have identified multiple plasma membrane signals that regulate the Rac GTPase, thus regulating WAVE and Arp2/3 complexes, to promote branched F-actin formation and polarized enrichment. We describe here a pathway that acts in parallel to Rac to transduce membrane signals to control epidermal F-actin through the GTPase Rho. Rho contributes to epidermal migrations through effects on underlying neuroblasts. Here we identify signals to regulate Rho in the epidermis. HUM-7, theC. eleganshomolog of human Myo9A and Myo9B, regulates F-actin dynamics during epidermal migrations, by controlling Rho. Genetics and biochemistry support that HUM-7 behaves as GAP for the Rho GTPase, so that loss of HUM-7 enhances Rho-dependent epidermal cell behaviors. We identify SAX-3/ROBO as an upstream signal that contributes to attenuated Rho activation through its regulation of HUM-7/Myo9. These studies identify a new role for Rho during epidermal cell migrations, and suggest that Rho activity is regulated by SAX-3/ROBO acting on the RhoGAP HUM-7.
DNA-segment-capture model for loop extrusion by structural maintenance of chromosome (SMC) protein complexes
Authors: Marko John F. , De Los Rios Paolo , Barducci Alessandro , Gruber Stephan 
Published: May 2018

AbstractCells possess remarkable control of the folding and entanglement topology of long and flexible chromosomal DNA molecules. It is thought that structural maintenance of chromosome (SMC) protein complexes play a crucial role in this, by organizing long DNAs into series of loops. Experimental data suggest that SMC complexes are able to translocate on DNA, as well as pull out lengths of DNA via a “loop extrusion” process. We describe a Brownian loop-capture-ratchet model for translocation and loop extrusion based on known structural, catalytic, and DNA-binding properties of theBacillus subtilisSMC complex. Our model provides an example of a new class of molecular motor where large conformational fluctuations of the motor ‘track’ - in this case DNA - are involved in the basic translocation process. Quantitative analysis of our model leads to a series of predictions for the motor properties of SMC complexes, most strikingly a strong dependence of SMC translocation velocity and step size on tension in the DNA track that it is moving along, with “stalling” occuring at subpiconewton tensions. We discuss how the same mechanism might be used by structurally related SMC complexes (E. coliMukBEF and eukaryote condensin, cohesin and SMC5/6) to organize genomic DNA.
On the design of treatment schedules that avoid chemotherapeutic resistance
Authors: Ma Y. , Newton P.K. 
Published: May 2018

We introduce a method of designing treatment schedules for a model three-component replicator dynamical system that avoids chemotherapeutic resistance by controlling and managing the competitive release of resistant cells in the tumor. We use an evolutionary game theory model with prisoner’s dilemma payoff matrix that governs the competition among healthy cells, chemo-sensitive cells, and chemo-resistant cells and the goal is to control the evolution of chemo-resistance via the competitive release mechanism. The method is based on nonlinear trajectory design and energy transfer methods first introduced in the orbital mechanics literature for Hamiltonian systems. By using the structure of the trajectories defined by solutions of the replicator system for different constant chemotherapeutic concentrations (which produces a curvilinear coordinate system spanning the full region), we construct periodic (closed) orbits by switching the chemo-dose at carefully chosen times and appropriate levels to design schedules that are superior to both maximum tolerated dose (MTD) schedules and low-dose metronomic (LDM) schedules, both of which ultimately lead to fixation of either sensitive cells or resistant cells. By keeping the three sub-populations of cells in competition with each other, neither the sensitive cell population nor the resitant cell population are able to dominate as we balance the populations indefinitely (closed periodic orbits), thereby avoiding fixation of the cancer cell population and re-growth of a resistant tumor. The schedules we design have the feature that they maintain a higher average population fitness than either the MTD or the LDM schedules.PACS numbers: 87.23.Kg; 87.55.de; 87.19.Xj; 87.19.lr
Foreign exchange exposure in Latin America: evidence for Spanish firms
Authors: Vivel-Búa María Milagros , Lado-Sestayo Rubén 
Published: May 2018

Objective
The purpose of this paper is to analyse the Spanish business sector’s economic exposure to currency risk in Latin America between 2010 and 2016, testing the effectiveness of hedging with derivatives for the reduction of this risk.

Methodology
Economic exposure is tested with the Jorion model (1990) using both a currency basket and an individualised analysis for the main currencies sustaining business activities between Spain and Latin America: the Mexican peso, Brazilian real, Argentine peso, Chilean peso, and Colombian peso. For the hedging analysis, dynamic panel data models were estimated using a generalised method of moments.

Results
The results reveal that the number of firms with significant economic exposure is sensitive to the temporal frequency of the observations. The evidence denotes that the firms’ export profile is predominant, both when considering a basket of Latin American currencies and when individually considering the five main pairs of currencies. The only exception is the Argentine peso, where firms’ import profile is slightly higher. The Chilean peso stands out as the currency with the greatest number of firms with significant exposure.

Originality
This work provides unpublished evidence on economic exposure to currency risk in Latin America in a recent period characterised by two main aspects: an important devaluation of some Latin American currencies with respect to the euro; and an enhancement of Spanish business activities in the region to favour growth during the recent recession of the Spanish economy.