bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal Protection Against Ischemia Reperfusion Injury: Hemoglobin-based Oxygen Carrier-201 Versus Blood as an Oxygen Carrier in Ex Vivo Subnormothermic Machine Perfusion
Authors: Bhattacharjee Rabindra N. , Patel Sanjay V.B. , Sun Qizhi , Jiang Larry , Richard-Mohamed Mahms , Ruthirakanthan Aushanth , Aquil Shahid , Al-Ogaili Rafid , Juriasingani Smriti , Sener Alp , Luke Patrick P.W.
Published: September 2019

Background.

The optimal method of oxygen delivery to donor kidneys during ex vivo machine perfusion has not been established. We have recently reported the beneficial effects of subnormothermic (22°C) blood perfusion in the preservation of porcine donation after circulatory death kidneys. Since using blood as a clinical perfusate has limitations, including matching availability and potential presence of pathogen, we sought to assess hemoglobin-based oxygen carrier (HBOC-201) in oxygen delivery to the kidney for renal protection.

Methods.

Pig kidneys (n = 5) were procured after 30 minutes of warm in situ ischemia by cross-clamping the renal arteries. Organs were flushed with histidine tryptophan ketoglutarate solution and subjected to static cold storage or pulsatile perfusion with an RM3 pump at 22°C for 4 hours with HBOC-201 and blood. Thereafter, kidneys were reperfused with normothermic (37°C) oxygenated blood for 4 hours. Blood and urine were subjected to biochemical analysis. Total urine output, urinary protein, albumin/creatinine ratio, flow rate, resistance were measured. Acute tubular necrosis, apoptosis, urinary kidney damage markers, neutrophil gelatinase-associated lipocalin 1, and interleukin 6 were also assessed.

Results.

HBOC-201 achieved tissues oxygen saturation equivalent to blood. Furthermore, upon reperfusion, HBOC-201 treated kidneys had similar renal blood flow and function compared with blood-treated kidneys. Histologically, HBOC-201 and blood-perfused kidneys had vastly reduced acute tubular necrosis scores and degrees of terminal deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate nick end labeling staining versus kidneys treated with cold storage. Urinary damage markers and IL6 levels were similarly reduced by both blood and HBOC-201.

Conclusions.

HBOC-201 is an excellent alternative to blood as an oxygen-carrying molecule in an ex vivo subnormothermic machine perfusion platform in kidneys.
Too Much, Too Little, or Just Right? The Importance of Allograft Portal Flow in Deceased Donor Liver Transplantation
Authors: Matsushima Hajime , Sasaki Kazunari , Fujiki Masato , Uso Teresa Diago , Aucejo Federico , Kwon Choon Hyuck David , Eghtesad Bijan , Miller Charles , Quintini Cristiano , Hashimoto Koji
Published: September 2019

Background.

While portal flow (PF) plays an important role in determining graft outcomes in living donor liver transplantation, its impact in deceased donor liver transplantation (DDLT) is unclear. The aim of this study was to investigate the correlations between graft PF and graft outcomes in DDLT.

Methods.

We retrospectively investigated 1001 patients who underwent DDLT between January 2007 and June 2017 at our institution. The patients were divided into 3 groups according to hazard ratio for 1-year graft loss at each PF value, which was standardized with graft weight. Graft and recipient outcomes were compared between the groups.

Results.

The low-PF group (PF < 65 mL/min/100 g, n = 210, P = 0.011) and the high-PF group (PF ≥ 155 mL/min/100 g, n = 159, P = 0.018) showed significantly poorer 1-year graft survival compared with the intermediate-PF group (PF ≥ 65 mL/min/100 g and < 155 mL/min/100 g, n = 632). The patients in the low-PF group had severe reperfusion injury and were more frequently complicated with primary nonfunction (P = 0.013) and early allograft dysfunction (P < 0.001) compared with the other groups. In contrast, the patients in the high-PF group had milder reperfusion injury, but had lower intraoperative hepatic artery flow with higher incidence of hepatic artery thrombosis (P = 0.043) and biliary complication (P = 0.041) compared with the other groups.

Conclusions.

These results suggest that intraoperative PF plays an important role in determining early graft outcomes after DDLT.
A unified sequence catalogue of over 280,000 genomes obtained from the human gut microbiome
Authors: Almeida Alexandre , Nayfach Stephen , Boland Miguel , Strozzi Francesco , Beracochea Martin , Shi Zhou Jason , Pollard Katherine S. , Parks Donovan H. , Hugenholtz Philip , Segata Nicola , Kyrpides Nikos C. , Finn Robert D.
Published: September 2019

Comprehensive reference data is essential for accurate taxonomic and functional characterization of the human gut microbiome. Here we present the Unified Human Gastrointestinal Genome (UHGG) collection, a resource combining 286,997 genomes representing 4,644 prokaryotic species from the human gut. These genomes contain over 625 million protein sequences used to generate the Unified Human Gastrointestinal Protein (UHGP) catalogue, a collection that more than doubles the number of gut protein clusters over the Integrated Gene Catalogue. We find that a large portion of the human gut microbiome remains to be fully explored, with over 70% of the UHGG species lacking cultured representatives, and 40% of the UHGP missing meaningful functional annotations. Intra-species genomic variation analyses revealed a large reservoir of accessory genes and single-nucleotide variants, many of which were specific to individual human populations. These freely available genomic resources should greatly facilitate investigations into the human gut microbiome.
RobNorm: Model-Based Robust Normalization Method for Labeled Quantitative Mass Spectrometry Proteomics Data
Authors: Wang Meng , Jiang Lihua , Jian Ruiqi , Chan Joanne Y. , Liu Qing , Snyder Michael P. , Tang Hua
Published: September 2019

Motivation

Data normalization is an important step in processing proteomics data generated in mass spectrometry (MS) experiments, which aims to reduce sample-level variation and facilitate comparisons of samples. Previously published methods for normalization primarily depend on the assumption that the distribution of protein expression is similar across all samples. However, this assumption fails when the protein expression data is generated from heterogenous samples, such as from various tissue types. This led us to develop a novel data-driven method for improved normalization to correct the systematic bias meanwhile maintaining underlying biological heterogeneity.

Methods

To robustly correct the systematic bias, we used the density-power-weight method to down-weigh outliers and extended the one-dimensional robust fitting method described in the previous work of (Windham, 1995, Fujisawa and Eguchi, 2008) to our structured data. We then constructed a robustness criterion and developed a new normalization algorithm, called RobNorm.

Results

In simulation studies and analysis of real data from the genotype-tissue expression (GTEx) project, we compared and evaluated the performance of RobNorm against other normalization methods. We found that the RobNorm approach exhibits the greatest reduction in systematic bias while maintaining across-tissue variation, especially for datasets from highly heterogeneous samples.

Availability

https://github.com/mwgrassgreen/RobNorm

Contact

huatang@stanford.eduandmpsnyder@stanford.edu
Laminar-specific cortico-cortical loops in mouse visual cortex
Authors: Young Hedi , Belbut Beatriz , Baeta Margarida , Petreanu Leopoldo
Published: September 2019

Many theories propose recurrent interactions across the cortical hierarchy, but it is unclear if cortical circuits are selectively wired to implement looped computations. Using subcellular channelrhodopsin-2-assisted circuit mapping in mouse visual cortex, we compared feedforward (FF) or feedback (FB) cortico-cortical input to cells projecting back to the input source (looped neurons) with cells projecting to a different cortical or subcortical area (non-looped neurons). Despite having different laminar innervation patterns, FF and FB afferents showed similar cell-type selectivity, making stronger connections with looped neurons versus non-looped neurons in layer (L) 5 and L6, but not in L2/3. FB inputs preferentially innervated the apical tufts of looped L5 neurons, but not their perisomatic dendrites. Our results reveal that interareal cortical connections are selectively wired into monosynaptic excitatory loops involving L6 and the apical dendrites of L5 neurons, supporting a role of these circuit elements in hierarchical recurrent computations.
An atlas of the tissue and blood metagenome in cancer reveals novel links between bacteria, viruses and cancer
Authors: Borchmann Sven
Published: September 2019

Host tissue infections by bacteria and viruses can cause cancer. Massively parallel sequencing now routinely generates datasets large enough to contain detectable traces of bacterial and viral nucleic acids of taxa that colonize the examined tissue or are integrated into the host genome. However, this hidden resource has not been comprehensively studied in large patient cohorts.

In the present study, 3000 whole genome sequencing datasets are leveraged to gain insight into novel links between viruses, bacteria and cancer. The resulting map confirms known links and expands current knowledge by identifying novel associations. Moreover, the detection of certain bacteria or viruses is associated with profound differences in patient and tumor phenotypes, such as patient age, tumor stage, survival, somatic mutations in cancer genes or gene expression profiles.

Overall, these results provide a detailed, unprecedented map of links between viruses, bacteria and cancer that can serve as a reference for future studies.
Surface association induces cytotoxic alkyl-quinolones in Pseudomonas aeruginosa
Authors: Vrla Geoffrey D. , Esposito Mark , Zhang Chen , Kang Yibin , Seyedsayamdost Mohammad R. , Gitai Zemer
Published: September 2019

Surface attachment, an early step in the colonization of multiple host environments, activates the virulence of the human pathogen P. aeruginosa. However, the signaling pathways and downstream toxins specifically induced by surface association to stimulate P. aeruginosa virulence are not fully understood. Here, we demonstrate that alkyl-quinolone (AQ) secondary metabolites are rapidly induced upon surface association and represent a major class of surface-dependent cytotoxins. AQ cytotoxicity is direct and independent of other AQ functions like quorum sensing or PQS-specific activities like iron sequestration. Furthermore, the regulation of AQ production can explain the surface-dependent virulence regulation of the quorum sensing receptor, LasR, and the pilin-associated candidate mechanosensor, PilY1. PilY1 regulates surface-induced AQ production by repressing the AlgR-AlgZ two-component system. AQs also contribute to the known cytotoxicity of secreted outer membrane vesicles. These findings collectively explain previously mysterious aspects of virulence regulation and provide new avenues for the development of anti-infectives.
Ongoing surveillance protects tanoak whilst conserving biodiversity: applying optimal control theory to a spatial simulation model of sudden oak death
Authors: Bussell E.H. , Cunniffe N.J.
Published: September 2019

The sudden oak death epidemic in California is spreading uncontrollably. Large-scale eradication has been impossible for some time. However, small-scale disease management could still slow disease spread. Although empirical evidence suggests localised control could potentially be successful, mathematical models have said little about such management. By approximating a detailed, spatially-explicit simulation model of sudden oak death with a simpler, mathematically-tractable model, we demonstrate how optimal control theory can be used to unambiguously characterise effective time-dependent disease management strategies. We focus on protection of tanoak, a tree species which is culturally and ecologically important, but also highly susceptible to sudden oak death. We identify management strategies to protect tanoak in a newly-invaded forest stand, whilst also conserving biodiversity. We find that thinning of bay laurel is essential early in the epidemic. We apply model predictive control, a feedback strategy in which both the approximating model and the control are repeatedly updated as the epidemic progresses. Adapting optimal control strategies in this way is vital for effective disease management. This feedback strategy is robust to parameter uncertainty, limiting loss of tanoak in the worst-case scenarios. However, the methodology requires ongoing surveillance to re-optimise the approximating model. This introduces an optimal level of surveillance to balance the high costs of intensive surveys against improved management resulting from better estimates of disease progress. Our study shows how detailed simulation models can be coupled with optimal control theory and model predictive control to find effective control strategies for sudden oak death. We demonstrate that control strategies for sudden oak death must depend on local management goals, and that success relies on adaptive strategies that are updated via ongoing disease surveillance. The broad framework allowing the use of optimal control theory on complex simulation models is applicable to a wide range of systems.
Inhibition of the Myocardin-Related Transcription Factor pathway increases efficacy of Trametinib in NRAS-mutant melanoma cell lines
Authors: Appleton Kathryn M. , Palsuledesai Charuta C. , Misek Sean A. , Blake Maja , Zagorski Joseph , Dexheimer Thomas S. , Neubig Richard R.
Published: September 2019

The Ras/MEK/ERK pathway has been the primary focus of targeted therapies in melanoma; it is aberrantly activated in almost 80% of human cutaneous melanomas (∼50% BRAFV600 mutations and ∼30% NRAS mutations). While targeted therapies have yielded success in BRAFV600 mutant melanoma patients, such therapies have been ineffective in NRAS mutant melanomas in part due to their cytostatic effects and primary resistance in this patient population. Here, we demonstrate that increased Rho/MRTF-pathway activation correlates with high intrinsic resistance to the MEK inhibitor, trametinib, in a panel of NRAS mutant melanoma cell lines. Combination of trametinib with the Rho/MRTF-pathway inhibitor, CCG-222740, synergistically reduced cell viability in NRAS mutant melanoma cell lines in vitro. Furthermore, the combination of CCG-222740 with trametinib induced apoptosis and reduced clonogenicity in SK-Mel-147 cells which have a high level of trametinib resistance. These findings suggest a role of the Rho/MRTF-pathway in intrinsic trametinib resistance in a subset of NRAS mutant melanoma cell lines and highlights the potential of concurrently targeting the Rho/MRTF-pathway and MEK in NRAS mutant melanomas.
A multi-tissue transcriptome analysis of human metabolites guides the interpretability of associations based on multi-SNP models for gene expression
Authors: Ndungu Anne , Payne Anthony , Torres Jason , van de Bunt Martijn , McCarthy Mark I.
Published: September 2019

There is particular interest in transcriptome-wide association studies (TWAS) - gene-level tests based on multi-SNP predictive models of gene expression - for identifying causal genes at loci associated with complex traits. However, interpretation of TWAS associations may be complicated by divergent effects of model SNPs on trait phenotype and gene expression. We developed an iterative modelling scheme for obtaining multi-SNP models of gene expression and applied this framework to generate expression models for 43 human tissues from the Genotype-Tissues Expression (GTEx) Project. We characterized the performance of single- and multi-SNP TWAS models for identifying causal genes in GWAS data for 46 circulating metabolites. We show that: (a) multi-SNP models captured more variation in expression than the topcis-eQTL (median 2 fold improvement); (b) predicted expression based on multi-SNP models was associated (FDR<0.01) with metabolite levels for 826 unique gene-metabolite pairs, but, after step-wise conditional analyses, 90% were dominated by a single eQTL SNP; (c) amongst the 35% of associations where a SNP in the expression model was a significantcis-eQTL and metabolomic-QTL (met-QTL), 92% demonstrated colocalization between these signals, but interpretation was often complicated by incomplete overlap of QTLs in multi-SNP models; (d) using a “truth” set of causal genes at 61 met-QTLs, the sensitivity was high (67%), but the positive predictive value was low, as only 8% of TWAS associations at met-QTLs involved true causal genes. These results guide the interpretation of TWAS and highlight the need for corroborative data to provide confident assignment of causality.
Dysregulation of external globus pallidus-subthalamic nucleus network dynamics in Parkinsonian mice
Authors: Kovaleski Ryan F. , Callahan Joshua W. , Chazalon Marine , Baufreton Jérôme , Bevan Mark D.
Published: September 2019

Reciprocally connected GABAergic external globus pallidus (GPe) and glutamatergic subthalamic nucleus (STN) neurons form a key, centrally-positioned network within the basal ganglia, a group of subcortical brain nuclei critical for voluntary movement. In Parkinson’s disease (PD) and its models, abnormal rates and patterns of GPe-STN network activity are linked to motor dysfunction. Using cell class-specific optogenetic identification and inhibition approaches during cortical slow-wave activity and activation, we report that in dopamine-depleted mice 1) D2 dopamine receptor expressing striatal projection neurons (D2-SPNs) are hyperactive 2) prototypic parvalbumin (PV)-expressing GPe neurons are excessively patterned by D2-SPNs 3) despite being disinhibited, STN neurons are not hyperactive 4) the STN opposes rather than facilitates abnormal striatopallidal patterning. Together with recent studies, these data argue that in Parkinsonian mice abnormal, temporally offset PV GPe neuron and STN activity results from increased striatopallidal transmission and that compensatory plasticity within the STN prevents its hyperactivity.
Genetic changes of P. vivax tempers host tissue-specific responses in Anopheles stephensi
Authors: Tevatiya Sanjay , Kumari Seena , Chauhan Charu , Singla Deepak , De Tanwee Das , Sharma Punita , Thomas Tina , Rani Jyoti , Pandey Kailash C , Pande Veena , Dixit Rajnikant
Published: September 2019

In our preceding study (Sharma et al., 2019; BioRxiv) we showed that in the gut lumen Plasmodium vivax follows a unique strategy of immuno-suppression by disabling gut flora proliferation. Here, we further demonstrate that post gut invasion, a shrewd molecular relationship with individual tissues such as midgut, hemocyte, salivary glands, and strategic changes in the genetic makeup of P. vivax favors its survival in the mosquito host. A transient suppression of ‘metabolic machinery by early oocysts, and increased immunity’ against late oocysts suggested a unique mechanism of gut homeostasis restoration and Plasmodium population regulation. Though a hyper immune response of hemocyte was a key to remove free circulating sporozoites, but a strong suppression of salivary metabolic activities, may favor successful survival of invaded sporozoites. Finally, genetic alteration of P. vivax ensures evasion of mosquito responses. Conclusively, our system-wide RNAseq analysis provides first genetic evidences of direct mosquito-Plasmodium interaction and establishes a functional correlation.

Author Summary

Malaria transmission dynamics is heavily influenced by mosquito –parasite interaction. When passing through tissue specific barriers, Plasmodium have to compromise by losing its own population, but genetic relation is unknown. To win the developmental race Plasmodium need to overcome two important immuno-physiological barriers. First one accounts an indirect 24-30hr long pre-invasive gut-microbe-parasite interaction in the gut lumen. And second one follows a direct post gut invasive 14-18 days interaction with midgut, hemocyte and salivary glands. During pre-invasive phase of interaction, we showed Plasmodium vivax follows immuno-suppression strategy by restricting microbial growth in the gut lumen. Here, we demonstrate that switch of parasite from one stage to another stage within mosquito vector is accompanied by genetic changes of parasite. Our data suggests genetic makeup change enables the parasite to manipulate the metabolism of mosquito tissues. This strategy not only clear off multifaceted mosquito’s tissue specific immune responses, but also favors Plasmodium own survival and transmission. Comprehending this tissue specific interaction between host and parasite at molecular level could provide new tool to intervene the plasmodium life cycle within vector.
The trajectory of gait development in mice
Authors: Akula Shyam , McCullough Katherine B. , Weichselbaum Claire , Dougherty Joseph D. , Maloney Susan E.
Published: September 2019

Gait irregularities are prevalent in neurodevelopmental diseases and disorders (NDDs). However, there is a paucity of information on gait phenotypes in the NDD experimental models. This is in part due to the lack of understanding of the normal developmental trajectory of gait maturation in the mouse. Using the DigiGait system, we have developed a quantitative, standardized, and reproducible assay of developmental gait metrics in commonly used mouse strains that can be added to the battery of mouse model phenotyping. With this assay, we characterized the trajectory of gait in the developing C57BL/6J and FVB/AntJ mouse lines. In both lines, maturation of mouse gait between P21 and P30 was best reflected by aspects of the stance phase of the stride. Additionally, in C57BL/6J mice, gait maturation was observed through how the paw is loaded and unloaded during the stance phase of a stride. In FVB/AntJ mice, gait maturity during this developmental window was best observed through the decreased variability in paw area on the belt during stance. Our results also underscore the importance of considering body length when interpreting gait metrics. Further, our results show that background strain needs to be considered when comparing gait across models. Overall, our results show that aspects of mouse gait development parallel a timeline of normal human gait development, such as the percent of stride that is stance phase and swing phase. This study may be used as a standard reference for developmental gait phenotyping of a variety of murine models, such as models of neurodevelopmental disease.
The power of mixed survey methodologies for detecting decline of the Bornean orangutan
Authors: Santika Truly , Wilson Kerrie A. , Meijaard Erik , Ancrenaz Marc
Published: September 2019

For many threatened species, it is difficult to assess precisely for large areas the change in their abundances over time and the relative impacts of climate and anthropogenic land use. This is because surveys of such species are typically restricted to small geographic areas, are conducted during short time periods, and use different survey protocols. We assessed the change in the abundance of Bornean orangutanPongo pygmaeus morioin Sabah, Malaysia, and to identify environmental drivers affecting the change by integrating different types of survey data. We used nest count data obtained from aerial and ground transect surveys and occurrence data obtained from reconnaissance walks and interview survey over the past decade. We built a spatially-explicit dynamic population model within the Bayesian framework allowing these varying survey data to be analyzed jointly by explicitly accounting for each survey’s sampling rate. We found that sampling rates vary across survey types, reflecting each survey’s associated effort. Orangutan survival rates were strongly determined by natural forest extent and moderately by temperature. Orangutan migration rates across more than 1 km distance between forest patches were low, which underlines the importance of maintaining ecological connectivity. The paucity of species abundance data collected in a consistent manner over many years across broad extents often hinders the assessment of species population trend and their persistence across regional scales. We demonstrate that this can be addressed by integrating multiple survey data across different localities, provided that sampling rate inherent to each survey is accounted for.
Multiple testing correction over contrasts for brain imaging
Authors: Alberton Bianca A. V. , Nichols Thomas E. , Gamba Humberto R. , Winkler Anderson M.
Published: September 2019

The multiple testing problem arises not only when there are many voxels or vertices in an image representation of the brain, but also when multiple contrasts of parameter estimates (that is, hypotheses) are tested in the same general linear model. Here we argue that a correction for this multiplicity must be performed to avoid excess of false positives. Various methods have been proposed in the literature, but few have been applied to brain imaging. Here we discuss and compare different methods to make such correction in different scenarios, showing that one classical and well known method is invalid, and argue that permutation is the best option to perform such correction due to its exactness and flexibility to handle a variety of common imaging situations.
Middle-down proteomics reveals dense sites of methylation and phosphorylation in arginine-rich RNA-binding proteins
Authors: Kundinger Sean R. , Bishof Isaac , Dammer Eric B. , Duong Duc M. , Seyfried Nicholas T.
Published: September 2019

Arginine (Arg)-rich RNA-binding proteins play an integral role in RNA metabolism. Post-translational modifications (PTMs) within Arg-rich domains, such as phosphorylation and methylation, regulate multiple steps in RNA metabolism. However, the identification of PTMs within Arg-rich domains with complete trypsin digestion is extremely challenging due to the high density of Arg residues within these proteins. Here, we report a middle-down proteomic approach coupled with electron transfer dissociation (ETD) mass spectrometry to map previously unknown sites of phosphorylation and methylation within the Arg-rich domains of U1-70K and structurally similar RNA-binding proteins from nuclear extracts of HEK293 cells. Remarkably, the Arg-rich domains in RNA-binding proteins are densely modified by methylation and phosphorylation compared with the remainder of the proteome, with di-methylation and phosphorylation favoring RSRS motifs. Although they favor a common motif, analysis of combinatorial PTMs within RSRS motifs indicate that phosphorylation and methylation do not often co-occur, suggesting they may functionally oppose one another. Collectively, these findings suggest that the level of PTMs within Arg-rich domains may be among the highest in the proteome, and a possible unexplored regulator of RNA metabolism. These data also serve as a resource to facilitate future mechanistic studies of the role of PTMs in RNA-binding protein structure and function.

Briefs

Middle-down proteomics reveals arginine-rich RNA-binding proteins contain many sites of methylation and phosphorylation.
Draft genome of a porcupinefish, Diodon Holocanthus
Authors: Xu Mengyang , Su Xiaoshan , Zhang Mengqi , Li Ming , Huang Xiaoyun , Fan Guangyi , Liu Xin , Zhang He
Published: September 2019

The long-spine porcupinefish, Diodon holocanthus (Diodontidae, Tetraodontiformes, Actinopterygii), also known as the freckled porcupinefish, attracts great interest of ecology and economy. Its distinct characteristics including inflation reaction, spiny skin and tetradotoxin, however, have not been fully studied without a complete genome assembly.

In this study, the whole genome of a single individual was sequenced using single tube-Long Fragment Read co-barcode reads, generating 154.3 Gb of paired-end data (219.8× depth). The gap was further filled using small amount of Oxford Nanopore MinION long read dataset (11.4Gb, 15.9× depth). Taking full use of long, medium, short-range of genome assembly information, the final assembled sequences with a total length of 650.02 Mb obtained contig and scaffold N50 sizes of 2.15 Mb and 8.13 Mb, respectively, despite of high repetitive content. Benchmarking Universal Single-Copy Orthologs captured 95.7% (2,474) of core genes to assess the completeness. In addition, 206.5 Mb (32.10%) of repetitive sequences were identified, and 20,840 protein-coding genes were annotated, among which 18,281 (87.72%) proteins were assigned with possible functions.

This is the first demonstration of de novo genome of the porcupinefish, which will benefit downstream analysis of ontogeny, phylogeny, and evolution, and improve the exploration of its unique defensive mechanism.
Distinctive tasks of different cyanobacteria and associated bacteria in carbon as well as nitrogen fixation and cycling in a late stage Baltic Sea bloom
Authors: Eigemann Falk , Vogts Angela , Voss Maren , Zoccarato Luca , Schulz-Vogt Heide
Published: September 2019

Cyanobacteria and associated heterotrophic bacteria hold key roles in carbon as well as nitrogen fixation and cycling in the Baltic Sea due to massive cyanobacterial blooms each summer. The species specific activities of different cyanobacterial species as well as the N- and C-exchange of associated heterotrophic bacteria in these processes, however, are widely unknown. Within one time series experiment we tested the cycling in a natural, late stage cyanobacterial bloom by adding13C bi-carbonate and15N2, and performed sampling after 10 min, 30 min, 1 h, 6 h and 24 h in order to determine the fixing species as well as the fate of the fixed carbon and nitrogen in the associations. Uptake of15N and13C isotopes by the most abundant cyanobacterial species as well as the most abundant associated heterotrophic bacterial groups was then analysed with a NanoSIMS. Overall, the filamentous, heterocystous speciesDolichospermumsp.,Nodulariasp., andAphanizomenonsp. revealed no or erratic uptake of carbon and nitrogen, indicating mostly inactive cells. In contrary, non-heterocystousPseudanabaenasp. dominated the nitrogen and carbon fixation, with uptake rates up to 1.49 ± 0.47 nmol N h-1l-1and 2.55 ± 0.91 nmol C h-1l-1. Associated heterotrophic bacteria dominated the subsequent nitrogen cycling with uptake rates up to 1.2 ± 1.93 fmol N h-1cell-1, but were also indicative for fixation of di-nitrogen.
Blood pressure variability from intra-arterial recordings in humans
Authors: Mukadam Farhan Adam , Gangadharan Naveen , Baskaran Bowya , Baskaran S , Subramani Kandasamy , Wankhar Syrpailyne , Devasahayam Suresh , Subramani Sathya
Published: September 2019

Systolic and diastolic blood pressures are reported as single point values by the non-invasive techniques used in clinical practice, while, in fact, they are highly varying signals. The objective of this study was to document the magnitude of variation of systolic and diastolic pressures over a few minutes by analysing intra-arterial pressure recordings made in 51 haemodynamically stable patients in an intensive care unit. Intra-arterial pressure data were acquired by a validated data acquisition system. Fast-Flush test was performed and the dynamic characteristics of the catheter transducer system namely natural frequency and damping co-efficient were calculated. Only those recordings with acceptable dynamic characteristics were included in the analysis. Power spectral calculation using the Discrete Fourier transform (DFT) of the pressure recording revealed two frequency peaks below the peak at heart rate. The lower and higher frequency peaks below the heart rate peak are referred to as Mayer and Traube waves in this study. Mayer wave peaks were observed in DFT spectra of 49 out of 51 patients. The Mayer wave frequency peaks ranged between 0.045 Hz to 0.065 Hz in 41 out of 51 patients. The frequency of Traube waves or the respiratory variations was more than 0.14 Hz. Three categories of systolic and diastolic pressure variabilities namely beat-to-beat variability, Respiratory variability (Traube wave amplitude) and Total magnitude of variation are reported for all 51 patients. The mean systolic and diastolic pressure variations (in a period of about 10 minutes) in the study sample were 21 ± 9 mm Hg and 14 ± 5 mm Hg respectively. Given the magnitude of systolic and diastolic pressure variations over a few minutes, the validity of reporting single point values for these pressures and using single point cut-offs for diagnosis and treatment of hypertension must be re-evaluated.
Coiled-coil registry shifts in the F684I mutant of Bicaudal result in cargo-independent activation of dynein motility
Authors: Cui Heying , Trybus Kathleen M. , Yusuf Ali M. , Goyal Puja , Zhang Kaiqi , Loh Jia Ying , Solmaz Sozanne R.
Published: September 2019

The dynein adaptorDrosophilaBicaudal D (BicD) is auto-inhibited and activates dynein motility only after cargo is bound, but the underlying mechanism is elusive. In contrast, we show that the full-length BicD/F684I mutant activates dynein processivity even in the absence of cargo. Our X-ray structure of the C-terminal domain of the BicD/F684I mutant reveals a coiled-coil registry shift; in the N-terminal region, the two helices of the homodimer are aligned, whereas they are vertically shifted in the wild-type. One chain is partially disordered and this structural flexibility is confirmed by computations, which reveal that the mutant transitions back and forth between the two registries. We propose that a coiled-coil registry shift upon cargo binding activates BicD for dynein recruitment. Moreover, the human homolog BicD2/F743I exhibits diminished binding of cargo adaptor Nup358, implying that a coiled-coil registry shift may be a mechanism to modulate cargo selection for BicD2–dependent transport pathways.
Fabrication of sharp silicon arrays to wound Caenorhabditis elegans
Authors: Belougne Jérôme , Ozerov Igor , Caillard Céline , Bedu Frédéric , Ewbank Jonathan J.
Published: September 2019

Understanding how animals respond to injury and how wounds heal remains a challenge. These questions can be addressed using genetically tractable animals, including the nematode Caenorhabditis elegans. Given its small size, the current methods for inflicting wounds in a controlled manner are demanding. To facilitate and accelerate the procedure, we fabricated regular arrays of pyramidal features (“pins”) sharp enough to pierce the tough nematode cuticle. The pyramids were made from monocrystalline silicon wafers that were micro-structured using optical lithography and alkaline wet etching. The fabrication protocol and the geometry of the pins, determined by electron microscopy, are described in detail. Upon wounding, C. elegans expresses genes encoding antimicrobial peptides. A comparison of the induction of antimicrobial peptide gene expression using traditional needles and the pin arrays demonstrates the utility of this new method.
The Evolution of Social Organization: Climate Influences Variation in Drosophilid Social Networks
Authors: Jezovit Jacob A. , Rooke Rebecca , Schneider Jonathan , Levine Joel D.
Published: September 2019

Cultural norms, collective decisions, reproductive behaviour, and pathogen transmission all emerge from interaction patterns within animal social groups. These patterns of interaction support group-level phenomena that can influence an individual’s fitness. The aim of this study is to understand the evolution of social organization in Drosophila. Using a comparative ecological, phylogenetic and behavioural approach, we studied the different properties of social interaction networks (SINs) formed by 20 drosophilids and the different ways these species interact. We investigate whether animal network structures arise from common ancestry, a response to the species’ past ecological environment, other social behaviours, or a combination of these factors. We demonstrate that differences in past climate predicted the species’ current SIN properties. The drosophilid phylogeny offered no value to predicting species’ differences in SINs through phylogenetic signal tests. This suggests group-level social behaviours in drosophilid species are shaped by divergent climates. However, we find that the distance at which flies interact correlated with the drosophilid phylogeny, indicating that behavioural elements that comprise SINs have remained largely unchanged in their recent evolutionary history. We find a significant correlation of leg length to social distance, outlining the interdependence of anatomy and complex social structures. Although SINs display a complex evolutionary relationship across drosophilids, this study provides evidence of selective pressures acting on social behaviour in Drosophila. We speculate that conserved molecular mechanisms may be shared across drosophilids deep in their evolutionary history, similar to other pervasive mechanisms, like biological clocks.
Analysis and subsequent molecular docking of selected phytochemicals with SLC6A3 and SLC6A4 as potential therapeutic agents for Obsessive-Compulsive Disorder (OCD)
Authors: Warshaneyan Swarn S. , Srivastava Prachi
Published: September 2019

Obsessive-Compulsive Disorder (OCD) is one of the most problematic disorders of the brain. It lies in the category of moodomics disorders and can be identified by the presence of recurring intrusive thoughts (“compulsions”) and urges to do certain things repeatedly (“obsessions”), with a definite lack of control on these tendencies and their intensity affecting the patient’s daily life. It is known to be associated with not only anxiety disorder but also depression, with its cause being unknown, although possessing genetic components. Several separate methods are being attempted to develop an effective therapy for OCD but this field of research requires more focus. In the present course of research, there is an attempt to signify the molecular analysis approach by testing potential drugs computationally with previously identified targets, i. e. dopamine active transporter (DAT or SLC6A3) and sodium-dependent serotonin transporter (SERT or 5-HTT or SLC6A4) – two proteins which have been observed playing a major role in the manifestation of OCD symptoms. Their 3D structure prediction has already been done in the previous course of study. In continuation to the previous study, there is an attempt to screen out the potentially useful phytochemicals against this moodomics disorder. Several potentially useful phytochemicals are known to associate with SLC6A3 and SLC6A4, which have been identified through the text mining of various publications. First of all, these phytochemicals are analysed through the use of Molinspiration software followed by selection of the ones suitable as drug candidates using Lipinski’s Rule of five and finally, best docking configurations identified using AutoDock 4 in order to obtain potential therapeutics for OCD patients. Nuciferine, Epicatechin (EC), Retinal, Aphidicolin and Salvinorin A are showing good docking scores but among all these phytochemicals, Nuciferin, an extract of Indian Lotus plant, appears to be the one most suitable compound on the basis of binding energy calculations. Hence, we can say this could be a good revealing therapeutic agent for this disorder.
Alignment of sample position and rotation during in situ synchrotron X-ray micro-diffraction experiments using a Laue cross-correlation approach
Authors: Zhang Chenglu , Zhang Yubin , Wu Guilin , Liu Wenjun , Xu Ruqing , Juul Jensen Dorte , Godfrey Andrew
Published: September 2019

Laue micro-diffraction has proven to be able to reveal material properties at the sub-grain scale for many polycrystalline materials and is now routinely available at several synchrotron facilities, providing an approach for nondestructive three-dimensional probing of the microstructures and mechanical states of materials. However, for in situ experiments, maintaining the positioning of the sample throughout the experiment, to achieve a good alignment of the characterized volumes, is a challenging issue. The aim of the present work is to address this problem by developing an approach based on digital image correlation of focused-beam Laue diffraction patterns. The method uses small changes in the diffraction signal as a focused X-ray beam is scanned over a surface region to allow corrections to be made for both sample lateral movement and rotation. The method is demonstrated using a tensile deformation experiment on an Al sample with 2.5 µm average grain size. The results demonstrate an accuracy of 0.5 µm for sample position registration and a precision in sample rotation of ∼0.01°. The proposed method is fast to implement and does not require the use of additional surface markers.
Crystal structure of the Fab region of a neutralizing antibody against granulocyte-macrophage colony-stimulating factor
Authors: Angkawidjaja Clement , Torashima Takashi
Published: September 2019

An increased level of granulocyte-macrophage colony-stimulating factor has a potential role in the development of autoimmune diseases, and the neutralization of its activity by monoclonal antibodies is a promising therapy for some diseases. Here, the crystal structure of the Fab region of EV1007, a fully human antibody expressed in Chinese hamster ovary cells that was developed from human peripheral blood mononuclear cells, is described. The structure closely resembles that of MB007, which is the Fab region of the same antibody expressed in Escherichia coli [Blech et al. (2012), Biochem. J.
447, 205–215], except at the hinge regions between the immunoglobulin domains and the H3 loop region. This paper presents evidence for the flexibility of the hinge and H3 loop regions of the antibody based on the comparison of two independently solved crystal structures.
Impact of consumer information acquisition confidence, social outcome confidence on information search and sharing
Authors: Zubair Ahsan , Shabbir Rizwan , Abro Muhammad Azeem , Mahmood Mahmood A. Husain
Published: September 2019

Purpose

This study aims to highlight the impact of information acquisition confidence and social outcome confidence on information search and information share intention. Moreover, the role of subjective knowledge is analyzed as a mediating variable among these relations.

Design/methodology/approach

This study conducted a survey which generated 233 valid responses. The data were analyzed using component factor analysis and structural equation modeling. Whereas, to examine the mediating effect, Hayes and Preacher (2008) model for statistical mediation analysis was used.

Findings

The results mainly supported the model by confirming that subjective knowledge, information acquisition confidence and social outcome confidence are positively related to information search intention. No association between information acquisition confidence and information sharing intention was found. The study's findings also suggested a positive association of social outcome confidence, subjective knowledge and information acquisition confidence with information share intention. Moreover, the results revealed that there is a significant and positive mediating effect of subjective knowledge between information acquisition confidence and information search intention. Subjective knowledge also acts as a mediator in the relationship between social outcome confidence and information sharing intention.

Practical implications

This study will be helpful for marketers and policymakers for designing marketing strategies which can enhance the flow of information. Moreover, this study will ensure the importance of information to marketers.

Originality/value

This paper fulfills an identified need to study the impact of consumer information acquisition confidence, social outcome confidence on information search and sharing with mediating role of subjective knowledge.
The scale of school organizational culture in Indonesia
Authors: Burhanuddin Burhanuddin
Published: September 2019

Purpose

The purpose of this paper is to develop a measurement model in order to investigate sorts of organizational cultures (OCs) existing in school organizations.

Design/methodology/approach

This study involved 300 teachers of Primary Schools in the Malang City, East Java Indonesia. It used a quantitative approach with structural equation modelling to develop a measurement model of school OC. To enable the measure of this variable to work, OC scale was constructed and validated employing a confirmatory factor analysis.

Findings

Results suggest items of the scale are conceptualized as unidimensional measure. The scale, thus, could be used to examine and properly identified types of OCs within a school setting.

Research limitations/implications

This study developed e-scale to measure OC within a school context. The measure was tested in referring to the data derived from a limited sample of primary school teachers in Malang City, Indonesia.

Practical implications

This study recommends that school principals are expected to create an OC to ensure the improvement of individual capacities is carried out effectively.

Originality/value

The investigation focused on a school OC as a complex project. Since not many research studies developed the scales to measure this specific cultural construct, the findings add to the theory in this area.
A hierarchical model to enhance financial and strategic performance of an oil and gas company in Malaysia
Authors: Krishnan Deven , Islam Rafikul , Sarif Suhaimi Mhd.
Published: September 2019

Purpose

The purpose of this study intends to develop a hierarchical model through prioritisation of the core competencies with respect to competitive advantage, financial and strategic performance for an oil and gas company in Malaysia.

Design/methodology/approach

Mixed method approach used in the present research. Initially, interviews were conducted to solicit information about the company’s core competencies, competitive advantage, and financial and strategic performance. The interview findings used for questionnaire development to rank core competencies with respect to competitive advantage, financial and strategic performance. The survey results were analysed using the analytic hierarchy process (AHP), a mathematical model and is synthesised using Super Decisions Software.

Findings

The study developed a hierarchical model and can be set as a benchmark for prioritising core competencies, with respect to competitive advantage, financial and strategic performance for oil and gas companies.

Practical implications

The prioritisation results will help the company considered in the present research and also the similar companies to optimise their resources and energy to focus on the desired and the most influential core competencies.

Social implications

As the oil industry develops competitive advantage, its success will cascade down to stimulate the nation’s growth, support industry and services expansion and eventually develop the nation.

Originality/value

This study is a first of its kind in using AHP to rank core competencies with respect to competitive advantage, financial and strategic performance for an oil and gas company. The results can be used by oil and gas companies to enhance their overall performance.