bluuebunny/crossref_metadata_2025 huggingface dataset:
Predator-prey nutrient competition undermines predator coexistence
Authors: Klauschies Toni , Gaedke Ursula
Published: January 2019

Contemporary theory of predator coexistence through relative non-linearity in their functional responses strongly relies on the Rosenzweig-MacArthur equations (1963) in which the (autotrophic) prey exhibits logistic growth in the absence of the predators. This implies that the prey is limited by a resource which availability is independent of the predators. This assumption does not hold under nutrient limitation where both prey and predators bind resources such as nitrogen or phosphorus in their biomass. Furthermore, the prey’s resource uptake-rate is assumed to be linear and the predator-prey system is considered to be closed. All these assumptions are unrealistic for many natural systems. Here, we show that predator coexistence on a single prey is strongly hampered when the prey and predators indirectly compete for the limiting resource in a flow-through system. In contrast, a non-linear resource uptake rate of the prey slightly promotes predator coexistence. Our study highlights that predator coexistence does not only depend on differences in the curvature of their functional responses but also on the type of resource constraining the growth of their prey. This has far-reaching consequences for the relative importance of fluctuation-dependent and -independent mechanisms of species coexistence in natural systems where autotrophs experience light or nutrient limitation.
PGC-1α overexpression partially rescues impaired oxidative and contractile pathophysiology following volumetric muscle loss injury
Authors: Southern William M. , Nichenko Anna S. , Tehrani Kayvan F. , McGranahan Melissa J. , Krishnan Laxminarayanan , Qualls Anita E. , Jenkins Nathan T. , Mortensen Luke J. , Yin Hang , Yin Amelia , Guldberg Robert E. , Greising Sarah M. , Call Jarrod A.
Published: January 2019

Volumetric muscle loss (VML) injury is characterized by a non-recoverable loss of muscle fibers due to ablative surgery or severe orthopaedic trauma, that results in chronic functional impairments of the soft tissue. Currently, the effects of VML on the oxidative capacity and adaptability of the remaining injured muscle are unclear. A better understanding of this pathophysiology could significantly shape how VML-injured patients and clinicians approach regenerative medicine and rehabilitation following injury. Herein, the data indicated that VML-injured muscle has diminished mitochondrial content and function (i.e. oxidative capacity), loss of mitochondrial network organization, and attenuated oxidative adaptations to exercise. However, forced PGC-1α over-expression rescued the deficits in oxidative capacity and muscle strength. This implicates physiological activation of PGC1-α as a limiting factor in VML-injured muscle adaptive capacity and provides a mechanistic target for regenerative rehabilitation approaches to address the skeletal muscle dysfunction.
Reliability and correlates of intra-individual variability in the oculomotor system
Authors: Perquin Marlou Nadine , Bompas Aline
Published: January 2019

Even if all external circumstances are kept equal, the oculomotor system shows intra-individual variability over time, affecting measures such as microsaccade rate, blink rate, pupil size, and gaze position. Recently, some of these measures have been associated with ADHD on a between-subject level. However, it remains unclear to what extent these measures constitute stable individual traits. In the current study, we investigate the intra-individual reliability of these oculomotor features. Combining results over three experiments (> 100 healthy participants), we find that most measures show good intra-individual reliability over different time points (repeatability) as well as over different conditions (generalisation). However, we find evidence against any correlation with self-assessed ADHD tendencies, mind wandering, and impulsivity. As such, the oculomotor system shows reliable intra-individual reliability, but its benefit for investigating self-assessed individual differences in healthy subjects remains unclear. With our results, we highlight the importance of reliability and statistical power when studying between-subject differences.
“Low-cost” initial burst of root development in wholeFagus crenataseedlings: The key to survival?
Authors: Kurosawa Yoko , Mori Shigeta , Wang Mofei , Ferrio Juan Pedro , Yamaji Keiko , Yoshimura Kenichi , Qur’ani Citra Gilang
Published: January 2019

Terrestrial plants are rooted in one place, and therefore their metabolism must be flexible to adapt to continuously changing environments. This flexibility is probably influenced by the divergent metabolic traits of plant organs. However, direct measurements on organ-specific metabolic rates are particularly scarce and little is known about their roles in determining whole-individual meatabolism. To reveal this on seedlings ofFagus crenata, which is one of the most widespread dominant genus in temperate deciduous broad leaf forests in the circum-polar Northern Hemisphere, we measured respiration, fresh mass and surface area for total leaves, stems and roots of 55 individuals in two years from germination and analyzed their relationships with individual metabolism. Proportion of roots to whole plant in mass increased from approximately 17% to 74%, and that in surface area increased from about 11% to 82% in the two years. Nonetheless, the increment of the proportion of root respiration to whole-plant respiration was from 9.2% to only 40%, revealing that the increment in mass and surface area of roots was much larger than the increment in energetic cost. As a result, only the roots showed a substantial decline in both respiration/surface area and respiration/mass among the three organs; roots had about 90% decline in their respiration/surface area, and 84% decline in their respiration/mass, while those in leaves and stems were relatively constant. The low-cost and rapid root development is specific to the two years after germination and would be effective for avoiding water and nutrient deficit, and possibly helps seedling survival. This drastic shift in structure and function with efficient energy use in developmental change from seeds to seedlings may underpin the establishment ofF. crenataforests. We discuss significance of lowering energetic cost for various individual organisms to effectively acquire resources from a wide perspective of view.
A Genome-engineered Bioartificial Implant for Autoregulated Anti-Cytokine Drug Delivery
Authors: Choi Yun-Rak , Collins Kelsey H. , Springer Luke E. , Pferdehirt Lara , Ross Alison K. , Wu Chia-Lung , Moutos Franklin T. , Harasymowicz Natalia S. , Brunger Jonathan M. , Pham Christine T.N. , Guilak Farshid
Published: January 2019

Biologic drug therapies are effective treatments for autoimmune diseases such as rheumatoid arthritis (RA) but may cause significant adverse effects, as they are administered continuously at high doses that can suppress the immune system. Using CRISPR-Cas9 genome editing, we engineered stem cells containing a synthetic gene circuit expressing biologic drugs to antagonize interleukin-1 (IL-1) or tumor necrosis factor (TNF) in an autoregulated, feedback-controlled manner in response to activation of the endogenous chemokine (C-C) motif ligand 2 (Ccl2) promoter. To test this approach in vivo, cells were tissue-engineered into a stable cartilaginous construct and implanted subcutaneously in mice with inflammatory arthritis. Bioengineered anti-cytokine implants mitigated arthritis severity as measured by joint pain, structural damage, and systemic and local inflammation. The coupling of synthetic biology with tissue engineering promises a range of potential applications for treating chronic diseases using custom-designed cells that express therapeutic transgenes in response to dynamically changing biological signals.
Transcranial photobiomodulation with infrared laser increases power of brain oscillations
Authors: Wang Xinlong , Dmochowski Jacek P. , Zeng Li , Kallioniemi Elisa , Husain Mustafa , Gonzalez-Lima F. , Liu Hanli
Published: January 2019

Non-invasive transcranial photobiomodulation with a 1064-nm laser (tPBML1064) has been reported to improve human performance on cognitive tasks as well as locally upregulate cerebral oxygen metabolism and hemodynamics. However, it is unknown whether tPBML1064 also modulates electrophysiology, and specifically neural oscillations, in the human brain. The hypothesis guiding this study was that tPBML1064 of the right prefrontal cortex enhances neurophysiological rhythms at specific frequency bands in the human brain under resting conditions. To test this hypothesis, we recorded the 64-channel scalp electroencephalogram (EEG) before, during, and after the application of 11 minutes of 4-cm-diameter tPBML1064 to the right forehead of human subjects (n=20) using a within-subject, sham-controlled design. Time-resolved scalp topographies of EEG power at five frequency bands were computed to examine tPBML1064-induced EEG power changes across the scalp. The results showed time-dependent, significant increases of EEG spectral powers at the alpha (8-13 Hz) and beta (13-30 Hz) bands at broad scalp regions, exhibiting a front-to-back pattern. The findings provide the first sham-controlled topographic mapping that tPBML1064 increases the strength of electrophysiological oscillations (alpha and beta bands), while also shedding light on the mechanisms of tPBM in the human brain.
Analysis of metabolic pathways in mycobacteria to aid drug-target identification
Authors: Bannerman Bridget P. , Vedithi Sundeep C. , Júlvez Jorge , Torres Pedro , Waman Vaishali P. , Munir Asma , Mendes Vitor , Malhotra Sony , Skwark Marcin J. , Oliver Stephen G. , Blundell Tom L.
Published: January 2019

Three related mycobacteria are the cause of widespread infections in man and are the focus of intense research and drug-discovery efforts in the face of growing antimicrobial resistance.Mycobacterium tuberculosis, the causative agent of tuberculosis, is currently one of the top ten causes of death in the world according to WHO;M.abscessus, a group of non-tuberculous mycobacteria causes lung infections and other opportunistic infections in humans; andM.leprae, the causative agent of leprosy, remains endemic in tropical countries. There is an urgent need to design alternatives to conventional treatment strategies, due to the increase in resistance to standard antibacterials. In this study, we present a comparative analysis of chokepoint and essentiality datasets that will provide insight into the development of new treatment regimes. We illustrate the key metabolic pathways shared between these three organisms and identify drug targets with a wide metabolic impact that are common to the three species. We demonstrate that 72% of the chokepoint enzymes are proteins essential toMycobacterium tuberculosis. We show also that 78% of the drug targets, prioritized based on their presence in multiple paths on the metabolic network, are present in pathways shared byM. tuberculosis, M.lepraeandM.abscessus, including biosynthesis of amino acids, carbohydrates, cell structures, fatty acid and lipid biosynthesis. A further 17% is found in the prioritised pathways shared betweenM. tuberculosisandM.abscessus. We have performed comparative structure modelling of potential drug targets identified using our analysis in order to assess druggability and demonstrate the importance of chokepoint analysis in terms of drug target identification.

AUTHOR SUMMARY

Computer simulation studies to design new drugs against mycobacteria
Genome-Wide Association Study and Pathway-Level Analysis of Kernel Color in Maize
Authors: Owens Brenda F. , Mathew Deepu , Diepenbrock Christine H. , Tiede Tyler , Wu Di , Mateos-Hernandez Maria , Gore Michael A. , Rocheford Torbert
Published: January 2019

Rapid development and adoption of biofortified, provitamin A-dense orange maize (Zea maysL.) varieties could be facilitated by a greater understanding of the natural variation underlying kernel color, including as relates to carotenoid biosynthesis and retention in maize grain. Greater abundance of carotenoids in maize kernels is generally accompanied by deeper orange color, useful for distinguishing provitamin A-dense varieties to consumers. While kernel color can be scored and selected with high-throughput, low-cost phenotypic methods within breeding selection programs, it remains to be well established as to what would be the logical genetic loci to target for selection for kernel color. We conducted a genome-wide association study of maize kernel color, as determined by colorimetry, in 1,651 yellow and orange inbreds from the Ames maize inbred panel. Associations were found withy1, encoding the first committed step in carotenoid biosynthesis, and withdxs2, which encodes the enzyme responsible for the first committed step in the biosynthesis of the isoprenoid precursors of carotenoids. These genes logically could contribute to overall carotenoid abundance and thus kernel color. ThelcyEandzep1genes, which can affect carotenoid composition, were also found to be associated with colorimeter values. A pathway-level analysis, focused on genes witha priorievidence of involvement in carotenoid biosynthesis and retention, revealed associations fordxs3anddmes1, involved in isoprenoid biosynthesis;ps1andvp5, within the core carotenoid pathway; andvp14, involved in cleavage of carotenoids. Collectively, these identified genes appear relevant to the accumulation of kernel color.
Genome-Scale reconstruction ofPaenarthrobacter aurescensTC1 metabolic model towards the study of atrazine bioremediation
Authors: Ofaim Shany , Zarecki Raphy , Porob Seema , Gat Daniella , Lahav Tamar , Xu Xihui , Kashi Yechezkel , Aly Radi , Jiang Jiandong , Eizenberg Hanan , Ronen Zeev , Freilich Shiri
Published: January 2019

Atrazine is an herbicide and pollutant of great environmental concern that is naturally biodegraded by microbial communities. The efficiency of biodegradation can be improved through the stimulating addition of fertilizers, electron acceptors, etc. In recent years, metabolic modelling approaches have become widely used as anin silicotool for organism-level phenotyping and the subsequent development of metabolic engineering strategies including biodegradation improvement. Here, we constructed a genome scale metabolic model,iRZ960, forPaenarthrobacter aurescensTC1 – a widely studied atrazine degrader - aiming at simulating its degradation activity. A mathematical stoichiometric metabolic model was constructed based on a published genome sequence ofP. aurescensTC1. An Initial draft model was automatically constructed using the RAST and KBase servers. The draft was developed into a predictive model through semi-automatic gap-filling procedures including manual curation. In addition to growth predictions under different conditions, model simulations were used to identify optimized media for enhancing the natural degradation of atrazine without a need in strain design via genetic modifications. Model predictions for growth and atrazine degradation efficiency were tested in myriad of media supplemented with different combinations of carbon and nitrogen sources that were verifiedin vitro. Experimental validations support the reliability of the model’s predictions for both bacterial growth (biomass accumulation) and atrazine degradation. Predictive tools, such as the presented model, can be applied for achieving optimal biodegradation efficiencies and for the development of ecologically friendly solutions for pollutant degradation in changing environments.
Variation in assembly stoichiometry in non-metazoan homologs of the hub domain of Ca2+/Calmodulin-dependent protein kinase II
Authors: McSpadden Ethan D. , Xia Zijie , Chi Chris C. , Susa Anna C. , Shah Neel H. , Gee Christine L. , Williams Evan R. , Kuriyan John
Published: January 2019

The multi-subunit Ca2+/calmodulin-dependent protein kinase II (CaMKII) holoenzyme plays a critical role in animal learning and memory. The kinase domain of CaMKII is connected by a flexible linker to a C-terminal hub domain that assembles into a 12- or 14-subunit scaffold that displays the kinase domains around it. Studies on CaMKII suggest that the stoichiometry and dynamic assembly/disassembly of hub oligomers may be important for CaMKII regulation. Although CaMKII is a metazoan protein, genes encoding predicted CaMKII-like hub domains, without associated kinase domains, are found in the genomes of some green plants and bacteria. We show that the hub domains encoded by three related green algae, Chlamydomonas reinhardtii, Volvox carteri f. nagarensis, and Gonium pectoral, assemble into 16-, 18-, and 20-subunit oligomers, as assayed by native protein mass spectrometry. These are the largest known CaMKII hub domain assemblies. A crystal structure of the hub domain from Chlamydomonas reinhardtii reveals an 18-subunit organization. We identified four intra-subunit hydrogen bonds in the core of the fold that are present in the Chlamydomonas hub domain, but not in metazoan hubs. When six point mutations designed to recapitulate these hydrogen bonds were introduced into the human CaMKII-α hub domain, the mutant protein formed assemblies with 14 and 16 subunits, instead of the normal 12- and 14-subunit assemblies. Our results show that the stoichiometric balance of CaMKII hub assemblies can be shifted readily by small changes in sequence.
Imprinted gene expression at theDlk1-Dio3cluster is controlled by both maternal and paternalIG-DMRs in a tissue-specific fashion
Authors: Alexander Katherine A. , García-García María J.
Published: January 2019

Imprinting at theDlk1-Dio3cluster is controlled by theIG-DMR, an imprinting control region differentially methylated between maternal and paternal chromosomes. The maternalIG-DMRis essential for imprinting control, functioning as acisenhancer element. Meanwhile, DNA methylation at the paternalIG-DMRis thought to prevent enhancer activity. To explore whether suppression of enhancer activity at the methylatedIG-DMRrequires the transcriptional repressor TRIM28, we analyzedTrim28chatwoembryos and performed epistatic experiments withIG-DMRdeletion mutants. We found that while TRIM28 regulates the enhancer properties of the paternalIG-DMR, it also controls imprinting through other mechanisms. Additionally, we found that the paternalIG-DMR, previously deemed dispensable for imprinting, is required in certain tissues, demonstrating that imprinting is regulated in a tissue-specific manner. Using PRO-seq to analyze nascent transcription, we identified 30 novel transcribed regulatory elements, including 23 that are tissue-specific. These results demonstrate that different tissues have a distinctive regulatory landscape at theDlk1-Dio3cluster and provide insight into potential mechanisms of tissue-specific imprinting control. Together, our findings challenge the premise thatDlk1-Dio3imprinting is regulated through a single mechanism and demonstrate that different tissues use distinct strategies to accomplish imprinted gene expression.
Variation in space and time: a long-term examination of density-dependent dispersal in a woodland rodent
Authors: Denomme-Brown Simon T. , Cottenie Karl , Falls J. Bruce , Falls E. Ann , Brooks Ronald J. , McAdam Andrew G.
Published: January 2019

Dispersal is a fundamental ecological process that can be affected by population density, yet studies report contrasting effects of density on propensity to disperse. Additionally, the relationship between dispersal and density is seldom examined using densities measured at different spatial scales or over extensive time-series. We used 51-years of trapping data to examine how dispersal by wild deer mice (Peromyscus maniculatus) was affected by changes in both local and regional population densities. We examined these patterns over both the entire time-series and also in ten-year shifting windows to determine whether the nature and strength of the relationship changed through time. Probability of dispersal decreased with increased local and regional population density, and the negative effect of local density on dispersal was more pronounced in years with low regional densities. Additionally, the strength of negative density-dependent dispersal changed through time, ranging from very strong in some decades to absent in other periods of the study. Finally, while females were less likely to disperse, female dispersal was more density-dependent than male dispersal. Our study shows that the relationship between density and dispersal is not temporally static and that investigations of density-dependent dispersal should consider both local and regional population densities.
Geographic Patterns of Bacterioplankton among Lakes of the Middle and Lower Reaches of the Yangtze River Basin, China
Authors: Bai Chengrong , Cai Jian , Zhou Lei , Jiang Xingyu , Hu Yang , Dai Jiangyu , Shao Keqiang , Tang Xiangming , Yang Xiangdong , Gao Guang
Published: January 2019

In aquatic ecosystems, microbial biogeography research is critical for unveiling the mechanisms of microbial community succession. However, little is known about the microbial biogeography among interconnected lakes. To address this deficit, we used high-throughput sequencing to explore geographic patterns and the relative importance of ecological processes that shape these patterns in abundant and rare bacterial subcommunities from 25 lakes across the middle and lower reaches of Yangtze River basin (MLYB, located in southeast China), where most of the lakes are interconnected by river networks. We found that there were significant differences in both abundant and rare bacterial subcommunities between the two lake groups that were far from each other, while were no difference among the nearby lakes in each group. Both abundant and rare bacteria followed a strong distance-decay relationship, especially for rare bacteria. These findings suggest that although the interconnectivity between lakes breaks the geographical isolation of bacteria, the dispersal capability of bacterial taxa was still limited by geographic distance. We also found that although deterministic processes and stochastic processes together drive the bacterial subcommunities assembly, the stochastic processes (based on adjusted R2 in redundancy analysis) exhibited a greater influence on bacterial subcommunities. Our results implied that bacterial dispersal among interconnected lakes was more stochastically.

Importance

Unraveling the relative importance of ecological processes regulating microbial community structure is a central goal in microbial ecology. In aquatic ecosystems, microbial communities often occur in spatially structured habitats, where connectivity directly affects dispersal and metacommunity processes. Recent theoretical work suggests that directional dispersal among connected habitats leads to higher variability in local diversity and among-community composition. However, the study of microbial biogeography among natural interconnected habitats is still lacking. The findings of this study revealed interesting phenomena of microbial biogeography among natural interconnected habitats, suggested that the high interconnectivity reduced the spatial heterogeneity of bacteria, and caused the dispersal of bacteria to be more stochastically. This study has provided a deeper understanding of the biogeographic patterns of rare and abundant bacterial taxa and their determined processes among interconnected aquatic habitats.
Comparison of expression profiling through microarray and RNA-seq analysis for Nipah virus
Authors: Rajput Akanksha , Kumar Manoj
Published: January 2019

The Nipah virus is responsible various outbreaks among countries of south east Asia, most recent is in Kerala, India. It is considered to be highly contagious and having a range of vectors for transmission. The condition worsens due to the lack of effective inhibitors. This study is first study, which focused to detect the differentially expressed genes among two different NiV studies from 2012 and 2017. The transcriptomic profiling data were retrieved from the sequence archives. The multivariate gene enrichment analyses were performed on the log transformed data from them using pathway, gene ontology, disease, reactome, etc. The comparison study suggests that the down regulated differentially expressed genes are common among them as compared to up regulated ones with statistical significance. However, among the diseased category the upregulated genes are mostly from metabolic pathways and diseased category like metabolic pathways, heart failure, cholesterol metabolism while the downregulated genes linked to various cancers, and viral diseases like hepatitis, dengue, influenza, etc. We found various small molecules mapped in the pathways which are differentially expressed among the studies, which could be targeted so as to control the Nipah infection. In order to design the inhibitors, our study would be useful to extract the effective and broad-spectrum drug targets.
Neuronal differentiation affects tissue mechanics and progenitor arrangement in the vertebrate neuroepithelium
Authors: Guerrero Pilar , Perez-Carrasco Ruben , Zagorski Marcin , Page David , Kicheva Anna , Briscoe James , Page Karen M.
Published: January 2019

Cell division, movement and differentiation contribute to pattern formation in developing tissues. This is the case in the vertebrate neural tube where neurons differentiate in a characteristic pattern from a highly dynamic proliferating pseudostratified epithelium. To investigate how progenitor proliferation and differentiation affect cell arrangement and growth of the neural tube, we use experimental measurements to develop a mechanical model of the apical surface of the neuroepithelium that incorporates inter-kinetic nuclear movement and spatially varying rates of neuronal differentiation. Simulations predict that tissue growth and the shape of lineage-related clones of cells differ with the rate of differentiation. Growth is isotropic in regions of high differentiation, but dorsoventrally biased in regions of low differentiation. This is consistent with experimental observations. The absence of directional signalling in the simulations indicates that global mechanical constraints are sufficient to explain the observed differences in anisotropy. This provides insight into how the tissue growth rate affects cell dynamics and growth anisotropy and opens up possibilities to study the coupling between mechanics, pattern formation and growth in the neural tube.
Bright near-infrared genetically encoded voltage indicator for all-optical electrophysiology
Authors: Monakhov Mikhail V. , Matlashov Mikhail E. , Colavita Michelangelo , Song Chenchen , Shcherbakova Daria M. , Antic Srdjan D. , Verkhusha Vladislav V. , Knöpfel Thomas
Published: January 2019

We developed genetically encoded voltage indicators (GEVIs) using bright near-infrared (NIR) fluorescent proteins from bacterial phytochromes. These new NIR GEVIs are optimized for combination of voltage imaging with simultaneous blue light optogenetic actuator activation. Iterative optimizations led to a GEVI here termed nirButterfly, which reliably reports neuronal activities including subthreshold membrane potential depolarization and hyperpolarization, as well as spontaneous spiking, or electrically- and optogenetically-evoked action potentials. This enables largely improved all-optical causal interrogations of physiology.
Identification of a Type IV CRISPR-Cas system located exclusively on IncHI1B/IncFIB plasmids in Enterobacteriaceae
Authors: Newire Enas , Aydin Alp , Juma Samina , Enne Virve I , Roberts Adam P.
Published: January 2019

During an investigation of CRISPR carriage in clinical, multi-drug resistant, Klebsiella pneumoniae, a novel CRISPR-Cas system (which we have designated Type IV-B) was detected on plasmids from two K. pneumoniae isolates from Egypt (isolated in 2002-2003) and a single K. pneumoniae isolate from the UK (isolated in 2017). Sequence analysis of other genomes available in GenBank revealed that this novel Type IV-B CRISPR-Cas system was present on 28 other plasmids from various Enterobacteriaceae hosts and was never found on the chromosome. Type IV-B is found exclusively on IncHI1B/IncFIB plasmids and is associated with multiple putative transposable elements. Type IV-B has a single repeat-spacer array (CRISPR1) upstream of the cas loci with some spacers matching regions of conjugal transfer genes of IncFIIK/IncFIB(K) plasmids suggesting a role in plasmid incompatibility. Expression of the cas loci was confirmed in available clinical isolates by RT-PCR; indicating the system is active. To our knowledge, this is the first report describing a new subtype within Type IV CRISPR-Cas systems exclusively associated with IncHI1B/IncFIB plasmids.

Importance

Here, we report the identification of a novel subtype of Type IV CRISPR-Cas that is expressed and exclusively carried by IncHI1B/IncFIB plasmids in Enterobacteriaceae, demonstrating unique evolutionarily juxtaposed connections between CRISPR-Cas and mobile genetic elements (MGEs). Type IV-B encodes a variety of spacers showing homology to DNA from various sources, including plasmid specific spacers and is therefore thought to provide specific immunity against plasmids of other incompatible groups (IncFIIK/IncFIB(K)). The relationship between Type IV-B CRISPR-Cas and MGEs that surround and interrupt the system is likely to promote rearrangement and be responsible for the observed variability of this type. Finally, the Type IV-B CRISPR-Cas is likely to co-operate with other cas loci within the bacterial host genome during spacer acquisition.
The synergistic antitumor effect of combined Anti-Human Epidermal Growth Factor Receptor 2 (HER2) antibody and Gamma Interferon therapy to Ab resistant breast cancer cells
Authors: Gocho Toshihiko , Tsuchiya Hiromichi , Kamijo Shotaro , Yamazaki Yoshitaka , Akita Yui , Sasaki Akiko , Kiuchi Yuji
Published: January 2019

Anti-HER2 antibody is molecular targeted antibody for cancer therapy. Approximately 20% of breast cancers are characterized by overexpression of HER2 protein. However, the recurrence rate was 30% and the metastasis rate was 18% one year after treatment of Anti-HER2 antibody for HER2 positive breast cancer. The resistance to antibody treatment is a major problem for patients. We previously reported that Anti-HER2 antibody and Gamma Interferon (IFN-γ) combined therapy showed higher anti-tumor effect than usual therapy in vitro and in vivo mouse experiments.

In this study, we evaluated whether anti-HER2 antibody and IFN-γ combined therapy shows good synergistic effect against drug resistant HER2 positive breast cancer cells and higher antitumor effect than conventional clinical treatment. The resistant cell lines were made under the continuous presence of antibody until cell growth was not affected by the drug. We divided the resistant cells into the appropriate number of groups, which we and treated with anti-cancer therapy. We evaluated the antitumor effect for both in vitro study and in vivo mouse xenograft model prepared with the same immunogenicity. And we investigated the differences of immunofluorescence staining of CD8, Gr-1 and PDL-1 in tissues, especially related to immunity system.

The combined therapy showed significantly higher anti-tumor effect than other groups in vitro and in vivo experiments. The combined therapy affects anti-tumor immunity in this immunofluorescence experiment. Taken together, we showed the possibility that combined therapy could be an effective treatment option for anti-HER2 antibody resistant breast cancer, helping patients suffering from cancer progression after developing treatment resistance.
Information recovery following a retrospective cue decreases with time
Authors: Nouri Asal , Ester Edward F.
Published: January 2019

Working memory (WM) performance can be enhanced by an informative cue presented during storage. This effect, termed a retrocue benefit, can be used to explore how observers prioritize information stored in WM to guide behavior. Recent studies have demonstrated that neural representations of task-relevant memoranda are strengthened following the appearance of a retrocue, suggesting that participants can consult alternative information stores to supplement active memory traces. Here, we sought to better understand the nature of these memory store(s) by asking whether they are subject to the same temporal degradation seen in active memory representations. We reconstructed and quantified representations of remembered positions from alpha-band EEG activity recorded while participants performed a retrospectively cued spatial WM task, and varied the temporal interval separating the encoding display and retrocue. Although we observed a partial recovery of location information in all cue conditions, the magnitude of recovery was linearly and inversely related to the timing of the retrocue. This suggests that participants’ ability to supplement active memory representations with information from additional memory stores is not static: the information maintained in these stores may be subject to temporal degredation, or the stores themselves may become more difficult to access with time.
What kind of video gamer are you?
Authors: Jimenez Nadia , San-Martin Sonia , Camarero Carmen , San Jose Cabezudo Rebeca
Published: January 2019

Purpose

This paper aims to attempt to understand the extent to which the effect of motivations on purchase intention varies for diverse segments of video gamers (depending on their personality).

Design/methodology/approach

Information was collected from 511 Spanish video game consumers. Structural equation modeling, clustering and multi-group analysis were then conducted to compare results between segments of gamers.

Findings

Results show that hedonic, social and mainly addiction motivations lead to purchase intention of game-related products. Moreover, the authors identify a typology of gamer that gives rise to differences in motivations-purchase intention links: Analysts include individuals who are essentially conscientious, prefer inventive or cognitive and simulation games and whose behavior is more influenced by hedonic and social motivations to play; socializers comprise individuals who are mainly extrovert and emotionally stable gamers and who prefer sports and strategy games. The motivations to play that affect their purchase intentions are mainly social; and sentinels include individuals that are unmindful and introvert, prefer inventive, cognitive, sports and simulation games, and whose social motivations drive their purchase intentions.

Originality/value

There are 2,200 million video gamers around the world, although it is assumed that this vast market is not homogeneous, which has implications for consumer motivations and purchase intention. However, the currently available classifications that address this challenge are rather limited. In this sense, the present paper provides valuable insights into understanding how personality offers a useful variable to segment consumers in the video game industry and how it moderates the effect of motivations on purchase behavior.
Regulation of reproductive processes with dynamic energy budgets
Authors: Muller Erik B. , Lika Konstadia , Nisbet Roger M. , Schultz Irvin R. , Casas Jérôme , Gergs André , Murphy Cheryl A. , Nacci Diane , Watanabe Karen H.
Published: January 2019

Linking organismal‐level processes to underlying suborganismal mechanisms at the molecular, cellular and organ level constitutes a major challenge for predictive ecological risk assessments. This challenge can be addressed with the simple bioenergetic models in the family of dynamic energy budget (DEB), which consist of a small number of state equations quantifying universal processes, such as feeding, maintenance, development, reproduction and growth.

Motivated by the need for process‐based models to evaluate the impact of endocrine disruptors on ecologically relevant endpoints, this paper develops and evaluates two general modelling modules describing demand‐driven feedback mechanisms within the DEB modelling framework exerted by gonads on the allocation of resources to production of reproductive matter.

These modules describe iteroparous, semelparous and batch‐mode reproductive strategies. The modules have a generic form with both positive and negative feedback components; species‐ and sex‐specific attributes of endocrine regulation can be added without changing the core of the modules.

We demonstrate that these modules successfully describe time‐resolved measurements of wet weight of body, ovaries and liver, egg diameter and plasma content of vitellogenin and oestradiol in rainbow trout (Oncorynchus mykiss) by fitting these models to published and new data, which require the estimation of less than two parameters per data type.

We illustrate the general applicability of the concept of demand‐driven allocation of resources to reproduction by evaluating one of the modules with data on growth and seed production of an annual plant, the common bean (Phaseolis vulgaris).

A plain language summary is available for this article.
Three‐dimensional geophysical characterization of the La Rambla and Zafra de Záncara anticlines (Loranca Basin, Central Spain)
Authors: Ayala C. , Rubio F.M. , Rey‐Moral C. , Reguera M.I. , Biete C.
Published: January 2019

The Zafra de Záncara anticline (also known as the El Hito anticline), located in the Loranca Cenozoic Basin (part of the Tagus Basin, Central Spain), had been studied by several oil companies during the late 1960s and early 1970s. In 2009, within the ‘Plan for selection and characterization of suitable structures of CO2 geological storage’, this anticline was selected as a potential CO2 storage site. A preliminary three‐dimensional geological model, based on five geological cross sections that were constrained with the interpretation of the available seismic profiles (that are rather old and do not have very good quality), was created. With the aim of improving the geological knowledge of the Zafra de Záncara anticline and helping to investigate the suitability of a nearby anticline, namely La Rambla, as another structural closure that might make it a possible CO2 storage site, a local gravity survey (1 station every km2) was carried out in the area, seven new geological cross sections, based on these existing seismic profiles and field geology, were build, and a new three‐dimensional geological model that included both anticlines, improved through three‐dimensional stochastic gravity inversion, was constructed. The densities needed for the geological formations of the model come from the analysis of rock samples, logging data from El Hito‐1 drillhole and petrophysical information from Instituto Geológico y Minero de España database. The inversion has improved the knowledge about the geometry of the anticlines’ traps and seals as well as the geometry of the basement relief and the structural relationship between basement and cover.
Association of Vitamin D Receptor Gene Polymorphism With the Risk of Nephrolithiasis
Authors: Yang Shi‐Kun , Song Na , Wang Yang‐Yang , Li Ai‐Mei , Liu Jun , Deng Fei , Zhan Ming , Zhang Wei , Han Ya‐Chun , Zhang Hao
Published: January 2019

This study aimed to explore the relationship between vitamin D receptor (VDR) gene polymorphisms and the risk of nephrolithiasis. All relevant trials were searched from multiple databases according to predefined criteria, the pooled OR and corresponding 95% CI were analyzed using Stata software. Seventeen studies involving 2441 cases and 2296 controls were included. The pooled analysis showed that VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with nephrolithiasis susceptibility either in Asian and in Caucasians populations. VDR TaqI gene polymorphism was associated with nephrolithiasis in the overall populations (T vs. t: OR = 0.84, 95% CI: 0.73–0.95, P = 0.006; TT vs. Tt + tt: OR = 0.79, 95% CI: 0.66–0.95, P = 0.010). In Asian population, VDR TaqI gene polymorphism also was associated with nephrolithiasis susceptibility (TT vs. Tt + tt: OR = 0.72, 95% CI: 0.55–0.93, P = 0.012; Tt vs. TT + tt: OR = 1.43, 95% CI: 1.00–2.05, P = 0.048). But TaqI gene polymorphism was not associated with nephrolithiasis risk in Caucasian populations (T vs. t: OR = 0.85, 95% CI: 0.72–1.00, P = 0.051; TT vs. Tt + tt: OR = 0.87, 95% CI: 0.68–1.10, P = 0.245; tt vs. Tt + TT: OR = 1.32, 95% CI: 0.86–2.01, P = 0.206; Tt vs. TT+ tt: OR = 0.98, 95% CI: 0.70–1.38, P = 0.931). VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with the risk of nephrolithiasis either in Asian and Caucasians populations, but VDR TaqI gene polymorphism was associated with nephrolithiasis in the Asian subjects.
LlpB represents a second subclass of lectin‐like bacteriocins
Authors: Ghequire Maarten G. K. , De Mot René
Published: January 2019

Bacteriocins are secreted bacterial proteins that selectively kill related strains. Lectin‐like bacteriocins are atypical bacteriocins not requiring a cognate immunity factor and have been primarily studied in Pseudomonas. These so‐called LlpAs are composed of a tandem of B‐lectin domains. One domain interacts with d‐rhamnose residues in the common polysaccharide antigen of Pseudomonas lipopolysaccharide (LPS). The other lectin domain is crucial for interference with the outer membrane protein assembly machinery by interacting with surface‐exposed loops of its central component BamA. Via genome mining, we identified a second subclass of Pseudomonas lectin‐like proteins, termed LlpB, consisting of a single B‐lectin domain. We show that these proteins also display bactericidal activity. Among LlpB‐resistant transposon mutants of an LlpB‐susceptible Pseudomonas strain, a major subset was hit in an acyltransferase gene, predicted to be involved in LPS core modification, hereby suggesting that LlpBs equally attach to LPS for surface anchoring. This indicates that LPS binding and target strain specificity are condensed in a single B‐lectin domain. The identification of this second subclass of lectin‐like bacteriocins further expands the toolbox of antibacterial warfare deployed by bacteria and holds potential for their integration in biotechnological applications.
Measuring pain—Physiological and self‐rated measurements in relation to pain stimulation and anxiety
Authors: Storm Hanne , Günther Anders , Sackey Peter Victor , Bernhardsson Jens , Bjärtå Anna
Published: January 2019

Introduction

The aim of the present study was to investigate how emotions influence pain, measured by one subjective self‐rated measure, the numeric rating scale (NRS), and one objective physiological measure, the number of skin conductance responses (NSCR).

Method

Eighteen volunteers were exposed to conditions with pictorial emotional stimuli (neutral, positive, negative), authentic ICU‐sound (noise, no‐noise) and electrical stimulation (pain, no‐pain) individually titrated to induce moderate pain. When using all combinations of picture inducing emotions, sound, and pain, each of these conditions (12 conditions lasting for 60 seconds each) were followed by pain ratings. Ratings of arousal (low to high) and valence (pleasant to unpleasant) were used as indicators of affective state for each condition. Mean NSCR was also measured throughout the experiment for each condition.

Results

Even though NRS and NSCR increased during painful stimuli, they did not correlate during the trial. However, NSCR was positively correlated with the strength of the electrical stimulation,r = 0.48,P = 0.046, whereas NRS showed positive correlations with the anxiety level, assessed by affective ratings (arousal,r = 0.61,P < 0.001, and valence,r = 0.37,P < 0.001).

Conclusions

The NRS was strongly influenced by affective state, with higher pain ratings during more anxiety‐like states, whereas NSCR correlated to the strength of electrical pain stimulation. That reported pain is moderated by anxiety, puts forward a discussion whether reduction of the anxiety level should be considered during analgesia treatment.
Reporting and interpreting missing health‐related quality of life data in intensive care trials: Protocol for a systematic review
Authors: Kjær Maj‐Brit Nørregaard , Madsen Martin Bruun , Møller Morten Hylander , Egerod Ingrid , Perner Anders
Published: January 2019

Background

Health‐related quality of life is often used as a patient‐important outcome in randomized clinical trials in the intensive care unit setting. Missing data are a challenge in randomized clinical trials as they hamper the interpretation of the results, but the extent and handling of missing health‐related quality of life data are unknown. Therefore, we aim to describe and evaluate the extent, pattern, and handling of missing health‐related quality of life data in randomized clinical trials conducted in the intensive care unit setting.

Methods

We will conduct a systematic review of randomized clinical trials in intensive care patients that report health‐related quality of life. We will systematically search the Cochrane Library, PubMed, excerpta medica database ovid, and cumulative index to nursing and allied health literature for relevant literature. We will follow the recommendations by the Cochrane Collaboration and the preferred reporting items for systematic review and meta‐analysis statement. We will extract information about missing data, including how the analyses and reporting of missing data were performed. We will assess the risk of systematic errors (bias) and compare the number of nonresponders vs responders in (a) low vs high risk of bias trials and in (b) small (n ≤ 100) vs large randomized clinical trials (n > 100).

Discussion

With this outlined systematic review, we will describe the handling of missing health‐related quality of life data in randomized clinical trials in the intensive care unit setting and the impact on the interpretation of results.

Systematic review registration

International Prospective Register of Systematic Reviews (PROSPERO): reg. no.: CRD42019118932.
Benefits of Rhythm Control and Rate Control in Recent‐onset Atrial Fibrillation: The HERMES‐AF Study
Authors: Martín Alfonso , Coll‐Vinent Blanca , Suero Coral , Fernández‐Simón Amparo , Sánchez Juan , Varona Mercedes , Cancio Manuel , Sánchez Susana , Carbajosa José , Malagón Francisco , Montull Eugeni , del Arco Carmen ,   on behalf of the HERMES‐AF investigators
Published: January 2019

Background

Although rhythm control has failed to demonstrate long‐term benefits over rate control in longstanding episodes of atrial fibrillation (AF), there is little evidence concerning recent‐onset ones. We analyzed the benefits of rhythm and rate control in terms of symptoms alleviation and need for hospital admission in patients with recent‐onset AF.

Methods

This was a multicenter, observational, cross‐sectional study with prospective standardized data collection carried out in 124 emergency departments (EDs). Clinical variables, treatment effectiveness, and outcomes (control of symptoms, final disposition) were analyzed in stable patients with recent‐onset AF consulting for AF‐related symptoms.

Results

Of 421 patients included, rhythm control was chosen in 352 patients (83.6%), a global effectiveness of 84%. Rate control was performed in 69 patients (16.4%) and was achieved in 67 (97%) of them. Control of symptoms was achieved in 396 (94.1%) patients and was associated with a heart rate after treatment ≤ 110 beats/min (odds ratio [OR] = 14.346, 95% confidence interval [CI] = 3.90 to 52.70, p < 0.001) and a rhythm control strategy (OR = 2.78, 95% CI = 1.02 to 7.61, p = 0.046). Sixty patients (14.2%) were admitted: discharge was associated with a rhythm control strategy (OR = 2.22, 95% CI = 1.20‐4.60, p = 0.031) and admission was associated with a heart rate > 110 beats/min after treatment (OR = 29.71, 95% CI = 7.19 to 123.07, p < 0.001) and acute heart failure (OR = 9.45, 95% CI = 2.91 to 30.65, p < 0.001).

Conclusion

In our study, recent‐onset AF patients in whom rhythm control was attempted in the ED had a high rate of symptoms' alleviation and a reduced rate of hospital admissions.