bluuebunny/crossref_metadata_2025 huggingface dataset:
Ab initio thermodynamics of liquid and solid water
Authors: Cheng Bingqing , Engel Edgar A. , Behler Jörg , Dellago Christoph , Ceriotti Michele
Published: January 2019

Thermodynamic properties of liquid water as well as hexagonal (Ih) and cubic (Ic) ice are predicted based on density functional theory at the hybrid-functional level, rigorously taking into account quantum nuclear motion, anharmonic fluctuations, and proton disorder. This is made possible by combining advanced free-energy methods and state-of-the-art machine-learning techniques. The ab initio description leads to structural properties in excellent agreement with experiments and reliable estimates of the melting points of light and heavy water. We observe that nuclear-quantum effects contribute a crucial

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to the stability of ice Ih, making it more stable than ice Ic. Our computational approach is general and transferable, providing a comprehensive framework for quantitative predictions of ab initio thermodynamic properties using machine-learning potentials as an intermediate step.
Ionic stress enhances ER–PM connectivity via phosphoinositide-associated SYT1 contact site expansion in
Arabidopsis
Authors: Lee Eunkyoung , Vanneste Steffen , Pérez-Sancho Jessica , Benitez-Fuente Francisco , Strelau Matthew , Macho Alberto P. , Botella Miguel A. , Friml Jiří , Rosado Abel
Published: January 2019

Significance

Interorganelle connectivity and nonvesicular information transfer are hallmarks of biological systems. These processes facilitate communication between organelles, allowing them to adapt to changing cellular environments. In plants, the endoplasmic reticulum (ER)–plasma membrane (PM) contact sites (EPCSs) physically connect the cortical ER and the PM, and act as general platforms for Ca
2+
homeostasis regulation and the cellular adaptation to environmental stresses. Our identification of ionic stress and PM phosphoinositides as enhancers of ER–PM connectivity advances our understanding of how stress influences interorganelle communication. Furthermore, our analyses of the spatiotemporal regulation of EPCS expansion highlights unique mechanisms that plants activate to maintain interorganelle communication during long-term exposure to environmental stress, not described in other eukaryotes.
The DNA walk and its demonstration of deterministic chaos—relevance to genomic alterations in lung cancer
Authors: Hewelt Blake , Li Haiqing , Jolly Mohit Kumar , Kulkarni Prakash , Mambetsariev Isa , Salgia Ravi
Published: January 2019

Motivation

Advancements in cancer genetics have facilitated the development of therapies with actionable mutations. Although mutated genes have been studied extensively, their chaotic behavior has not been appreciated. Thus, in contrast to naïve DNA, mutated DNA sequences can display characteristics of unpredictability and sensitivity to the initial conditions that may be dictated by the environment, expression patterns and presence of other genomic alterations. Employing a DNA walk as a form of 2D analysis of the nucleotide sequence, we demonstrate that chaotic behavior in the sequence of a mutated gene can be predicted.

Results

Using fractal analysis for these DNA walks, we have determined the complexity and nucleotide variance of commonly observed mutated genes in non-small cell lung cancer, and their wild-type counterparts. DNA walks for wild-type genes demonstrate varying levels of chaos, with BRAF, NTRK1 and MET exhibiting greater levels of chaos than KRAS, paxillin and EGFR. Analyzing changes in chaotic properties, such as changes in periodicity and linearity, reveal that while deletion mutations indicate a notable disruption in fractal ‘self-similarity’, fusion mutations demonstrate bifurcations between the two genes. Our results suggest that the fractals generated by DNA walks can yield important insights into potential consequences of these mutated genes.

Availability and implementation

Introduction to Turtle graphics in Python is an open source article on learning to develop a script for Turtle graphics in Python, freely available on the web at https://docs.python.org/2/library/turtle.html. cDNA sequences were obtained through NCBI RefSeq database, an open source database that contains information on a large array of genes, such as their nucleotide and amino acid sequences, freely available at https://www.ncbi.nlm.nih.gov/refseq/. FracLac plugin for Fractal analysis in ImageJ is an open source plugin for the ImageJ program to perform fractal analysis, free to download at https://imagej.nih.gov/ij/plugins/fraclac/FLHelp/Introduction.html.

Supplementary information

Supplementary data are available at Bioinformatics online.
Breaking the paradigm: Dr Insight empowers signature-free, enhanced drug repurposing
Authors: Chan Jinyan , Wang Xuan , Turner Jacob A , Baldwin Nicole E , Gu Jinghua
Published: January 2019

Motivation

Transcriptome-based computational drug repurposing has attracted considerable interest by bringing about faster and more cost-effective drug discovery. Nevertheless, key limitations of the current drug connectivity-mapping paradigm have been long overlooked, including the lack of effective means to determine optimal query gene signatures.

Results

The novel approach Dr Insight implements a frame-breaking statistical model for the ‘hand-shake’ between disease and drug data. The genome-wide screening of concordantly expressed genes (CEGs) eliminates the need for subjective selection of query signatures, added to eliciting better proxy for potential disease-specific drug targets. Extensive comparisons on simulated and real cancer datasets have validated the superior performance of Dr Insight over several popular drug-repurposing methods to detect known cancer drugs and drug–target interactions. A proof-of-concept trial using the TCGA breast cancer dataset demonstrates the application of Dr Insight for a comprehensive analysis, from redirection of drug therapies, to a systematic construction of disease-specific drug-target networks.

Availability and implementation

Dr Insight R package is available at https://cran.r-project.org/web/packages/DrInsight/index.html.

Supplementary information

Supplementary data are available at Bioinformatics online.
i6mA-Pred: identifying DNA N6-methyladenine sites in the rice genome
Authors: Chen Wei , Lv Hao , Nie Fulei , Lin Hao
Published: January 2019

Motivation

DNA N6-methyladenine (6mA) is associated with a wide range of biological processes. Since the distribution of 6mA site in the genome is non-random, accurate identification of 6mA sites is crucial for understanding its biological functions. Although experimental methods have been proposed for this regard, they are still cost-ineffective for detecting 6mA site in genome-wide scope. Therefore, it is desirable to develop computational methods to facilitate the identification of 6mA site.

Results

In this study, a computational method called i6mA-Pred was developed to identify 6mA sites in the rice genome, in which the optimal nucleotide chemical properties obtained by the using feature selection technique were used to encode the DNA sequences. It was observed that the i6mA-Pred yielded an accuracy of 83.13% in the jackknife test. Meanwhile, the performance of i6mA-Pred was also superior to other methods.

Availability and implementation

A user-friendly web-server, i6mA-Pred is freely accessible at http://lin-group.cn/server/i6mA-Pred.
Integration of Differential Graded Manifolds
Authors: Ševera Pavol , Širaň Michal
Published: January 2019

We consider the problem of integration of $L_\infty $-algebroids (differential non-negatively graded manifolds) to $L_\infty $-groupoids. We first construct a “big” Kan simplicial manifold (Fréchet or Banach) whose points are solutions of a (generalized) Maurer–Cartan equation. The main analytic trick in our work is an integral transformation sending the solutions of the Maurer–Cartan equation to closed differential forms. Following the ideas of Ezra Getzler, we then impose a gauge condition that cuts out a finite-dimensional simplicial submanifold. This “smaller” simplicial manifold is (the nerve of) a local Lie $\ell $-groupoid. The gauge condition can be imposed only locally in the base of the $L_\infty $-algebroid; the resulting local $\ell $-groupoids glue up to a coherent homotopy, that is, we get a homotopy coherent diagram from the nerve of a good cover of the base to the (simplicial) category of local $\ell $-groupoids. Finally, we show that a $k$-symplectic differential non-negatively graded manifold integrates to a local $k$-symplectic Lie $\ell$-groupoid; globally, these assemble to form an $A_\infty$-functor. As a particular case for $k=2$, we obtain integration of Courant algebroids.
Prime Predator: Amazon and the Rationale of Below Average Variable Cost Pricing Strategies Among Negative-Cash Flow Firms
Authors: Sussman Shaoul
Published: January 2019

American jurisprudence considers price predation a largely irrational, and therefore self-limiting, business strategy which is unlikely to lead to monopolization of an industry. This paper argues that the recent rise of the negative cash flow firm upends traditional assumptions. These types of firms can achieve greater market share through predatory pricing strategies that involve long-term below average variable cost prices. It also maintains that recoupment, an essential element of any predatory pricing scheme, can be achieved without a raise of prices post predation. By charging prices in the present reflecting future lower costs based on prospective technological and scale efficiencies, these firms are able to rationalize their predatory pricing practices to investors and shareholders. These observations lead to the conclusion that price predation is a rational strategy which can foreseeably lead to monopolization. This paper then moves on to examine the conduct of Amazon, the biggest negative cash flow firm in the world. It suggests that not only is it entirely rational for Amazon to engage in price predation and a long-term strategy of monopolization but that under current corporate disclosure rules such conduct would be virtually undetectable. The negative impact of this behavior is the elimination present and future competition.
Quantifying risk factors in medical reports with a context-aware linear model
Authors: Przybyła Piotr , Brockmeier Austin J , Ananiadou Sophia
Published: January 2019

Objective

We seek to quantify the mortality risk associated with mentions of medical concepts in textual electronic health records (EHRs). Recognizing mentions of named entities of relevant types (eg, conditions, symptoms, laboratory tests or behaviors) in text is a well-researched task. However, determining the level of risk associated with them is partly dependent on the textual context in which they appear, which may describe severity, temporal aspects, quantity, etc.

Methods

To take into account that a given word appearing in the context of different risk factors (medical concepts) can make different contributions toward risk level, we propose a multitask approach, called context-aware linear modeling, which can be applied using appropriately regularized linear regression. To improve the performance for risk factors unseen in training data (eg, rare diseases), we take into account their distributional similarity to other concepts.

Results

The evaluation is based on a corpus of 531 reports from EHRs with 99 376 risk factors rated manually by experts. While context-aware linear modeling significantly outperforms single-task models, taking into account concept similarity further improves performance, reaching the level of human annotators’ agreements.

Conclusion

Our results show that automatic quantification of risk factors in EHRs can achieve performance comparable to human assessment, and taking into account the multitask structure of the problem and the ability to handle rare concepts is crucial for its accuracy.
Offshoring the Border: The 1981 United States–Haiti Agreement and the Origins of Extraterritorial Maritime Interdiction
Authors: Tennis Katherine H.
Published: January 2019

Extraterritorial maritime interdiction is a common tactic used by destination states to keep unwanted migrants from reaching their borders. But it is problematic, raising legal concerns about refoulement as well as political concerns about sovereignty. Where did extraterritorial interdiction come from, and how has it become so widespread? This article draws on archival sources and contemporaneous legal opinions from within the Reagan administration to tell the origin story of the pivotal 1981 United States–Haiti agreement that pioneered this model of border control. Even at the time of adoption, this agreement faced legal challenges, and was viewed as a solution of last resort. Yet many of the legal challenges of modern extraterritorial interdiction trace back to the unique circumstances shaping this first agreement—including the need to cooperate with countries of embarkation, anticipatory determination of attempted entry and the offshoring of protection responsibilities. They were locked in by path-dependent feedback mechanisms domestically and then diffused internationally.
Middleman Minorities and Ethnic Violence: Anti-Jewish Pogroms in the Russian Empire
Authors: Grosfeld Irena , Sakalli Seyhun Orcan , Zhuravskaya Ekaterina
Published: January 2019

Using detailed panel data from the Pale of Settlement area between 1800 and 1927, we document that anti-Jewish pogroms—mob violence against the Jewish minority—broke out when economic shocks coincided with political turmoil. When this happened, pogroms primarily occurred in places where Jews dominated middleman occupations, i.e., moneylending and grain trading. This evidence is inconsistent with the scapegoating hypothesis, according to which Jews were blamed for all misfortunes of the majority. Instead, the evidence is consistent with the politico-economic mechanism, in which Jewish middlemen served as providers of insurance against economic shocks to peasants and urban grain buyers in a relationship based on repeated interactions. When economic shocks occurred in times of political stability, rolling over or forgiving debts was an equilibrium outcome because both sides valued their future relationship. In contrast, during political turmoil, debtors could not commit to paying in the future, and consequently, moneylenders and grain traders had to demand immediate (re)payment. This led to ethnic violence, in which the break in the relationship between the majority and Jewish middlemen was the igniting factor.
Ecological causes of uneven mammal diversity
Authors: Upham Nathan S. , Esselstyn Jacob A. , Jetz Walter
Published: January 2019

The uneven distributions of species over geography (e.g., tropical versus temperate regions) and phylogeny (e.g., rodents and bats versus the aardvark) are prominent biological patterns for which causal interconnections remain enigmatic. Here we investigate this central issue for living mammals using time-sliced clades sampled from a comprehensive recent phylogeny (N=5,911 species, ∼70% with DNA) to assess how different levels of unsampled extinction impact the inferred causes of species richness variation. Speciation rates are found to strongly exceed crown age as a predictor of clade species richness at every time slice, rejecting a clock-like model in which the oldest clades are the most speciose. Instead, mammals that are low-vagility or daytime-active show the fastest recent speciation and greatest extant richness. This suggests primary roles for dispersal limitation leading to geographic speciation (peripatric isolation) and diurnal adaptations leading to ecological speciation (time partitioning). Rates of speciation are also faster in temperate than tropical lineages, but only among older clades, consistent with the idea that many temperate lineages are ephemeral. These insights, enabled by our analytical framework, offer straightforward support for ecological effects on speciation-rate variation among clades as the primary cause of uneven phylogenetic richness patterns.
The BD2 domain of BRD4 is a determinant in EndoMT and vein graft neointima formation
Authors: Zhang Mengxue , Wang Bowen , Urabe Go , Huang Yitao , Plutzky Jorge , Kent K. Craig , Guo Lian-Wang
Published: January 2019

Background

Vein-graft bypass is commonly performed to overcome atherosclerosis but is limited by high failure rates, principally due to neointimal wall thickening. Recent studies reveal that endothelial-mesenchymal transition (EndoMT) is critical for vein-graft neointima formation. BETs are a family of Bromo/ExtraTerminal domains-containing epigenetic reader proteins (BRD2, BRD3, BRD4). They bind acetylated histones through their unique tandem bromodomains (BD1, BD2), facilitating transcriptional complex formation and cell-state transitions. The role for BETs, including individual BRDs and their unique BDs, is not well understood in EndoMT and neointimal formation.

Methods and Results

Repression of BRD4 expression abrogated TGFβ1-induced EndoMT, with greater effects than BRD2 or BRD3 knockdown. An inhibitor selective for BD2 in all BETs, but not that for BD1, blocked EndoMT. Moreover, expression of a dominant-negative BRD4-specific BD2 fully abolished EndoMT. Concordantly, BRD4 knockdown repressed TGFβ1-stimulated increase of ZEB1 protein – a transcription factor integral in EndoMT. In vivo, lentiviral gene transfer of either BRD4 shRNA or dominant negative BRD4-specific BD2 mitigated neointimal development in rat jugular veins grafted to carotid arteries.

Conclusions

Our data reveal the BD2 domain of BRD4 as a determinant driving EndoMT in vitro and neointimal formation in vivo. These findings provide new insight into BET biology, while offering prospects of specific BET domain targeting as an approach to limiting neointima and extending vein graft patency.
Specific domains of early parenting, their heritability and differential association with adolescent behavioural and emotional disorders and academic achievement
Authors: Culpin Iryna , Bornstein Marc H. , Putnick Diane L. , Sallis Hannah , Lee Ruby , Cordero Miguel , Rajyaguru Priya , Kordas Katarzyna , Cadman Tim , Pearson Rebecca M.
Published: January 2019

Background

Variations in parenting across large populations have rarely been described. It also remains unclear which specific domains of parenting are important for which specific offspring developmental outcomes. The study describes different domains of early parenting behaviours, their genetic heritability, and then determines the extent to which specific domains of parenting are associated with later offspring outcomes.

Methods

Parenting behaviours (birth to 3 years) were extracted from self-reported questionnaires administered to 12,358 mothers from the UK-based birth cohort study, the Avon Longitudinal Study of Parents and Children, and modelled as a latent factor using Confirmatory Factor Analysis. Genetic heritability and correlations between parenting factors were estimated using wide complex trait analysis. Offspring emotional, behavioural and academic outcomes were assessed at age 16 years using the self-reported Short Mood and Feelings Questionnaire, the Development and Well-Being Assessment, and grades achieved in national English Language examination.

Results

Three parenting factors were derived: parental enjoyment, conflictual relationships and stimulation; all showed low genetic heritability. There was no evidence of associations between parenting factors and offspring depressed mood. Stimulation was associated with better English grades after controlling for maternal education (standardised β=0.058, p=0.007), and enjoyment was negatively associated with English grades (β=-0.082, p=0.002). Conflictual relationships were associated with higher risk of offspring behavioural disorders after controlling for behavioural problems at age 3 years (β=0.227, p=0.007). Higher enjoyment reduced the association between conflict and behavioural problems (interaction term β=0.113, p<0.001).

Conclusions

We found evidence for predictive specificity of early parenting domains for offspring outcomes in adolescence. Early stimulation, unlike enjoyment, promoted later educational achievement. Conflictual relationships were associated with greater risk of behavioural problems, buffered by increased enjoyment. These findings hold implications for parenting interventions, guiding their focus according to specificity of parenting domains and their long-term outcomes in children.
The future of a partially effective HIV vaccine: assessing limitations at the population level
Authors: Selinger Christian , Dimitrov Dobromir T. , Welkhoff Philip , Bershteyn Anna
Published: January 2019

Objectives

Mathematical models have unanimously predicted that a first-generation HIV vaccine would be useful and cost-effective to roll out, but that its overall impact would be insufficient to reverse the epidemic. Here, we explore what factors contribute most to limiting the impact of such a vaccine.

Methods

Ranging from a theoretical ideal to a more realistic regimen, mirroring the one used in the currently ongoing trial in South Africa (HVTN 702), we model a nested hierarchy of vaccine attributes such as speed of roll-out, efficacy, and retention of booster doses.

Results

The predominant reasons leading to a substantial loss of vaccine impact on the HIV epidemic are the time required to scale up mass vaccination, limited durability and waning of efficacy.

Conclusions

A partially effective HIV vaccine will be a critical milestone for the development of a highly effective, durable, and scalable next-generation vaccine. Accelerated development, expedited vaccine availability, and improved immunogenicity are the main attributes of a vaccine that could dramatically reverse the course of the epidemic in highly endemic countries.
Automation for the identification of Pseudomonas aeruginosa: Comparison of TDR-300B, VITEK®2 and VITEK®-MS
Authors: Moehario Lucky H , Boestami Hans P , Edbert Daniel , Tjoa Enty , Robertus T
Published: January 2019

Quick and precise methods have always been needed in the medical field to correctly identify the agent of infection. Automated systems for diagnosis of infectious pathogen such Pseudomonas aeruginosa from critical patients with infections in the Intensive Care Unit is essential. This study aimed to compare the capability of automated biochemistry-based identification system, TDR-300B and VITEK®2, to the one of Matrix-Assisted Laser Desorption/Ionization - Time of Flight (MALDI-TOF), VITEK®-MS, in the identification of P. aeruginosa.

Samples were P. aeruginosa isolates collection from Laboratory of Microbiology, Faculty of Medicine and Health Science UNIKA Atma Jaya. These isolates were refreshed; one single colony of oxidase-positive Gram-negative rods was further inoculated in TDR-300B NF-64 cards and VITEK®2 GN cassettes. The bacterial identification was also carried out using VITEK®-MS as gold-standard. Positivity of TDR-300B and VITEK®2 in the identification of P. aeruginosa was 87.09% (27/31) and 90.32% (28/31) in the species level, and 87.09%, 96.77% in the genus level respectively. The congruity of TDR-300B/ VITEK®2 in the species and genus level was 83.87% and 87.09%. When compared to VITEK®-MS, congruence of VITEK®2 was 93.30% (24/26) and TDR-300B was 80.76% (21/26). Sensitivity value for TDR-300B and VITEK®2 was high, 95.45% and 100%, positive predictive value and accuracy were lower in TDR-300B than VITEK®2; Fisher’ exact value was >0.05, thus there were no significant differences in the capability of TDR-300B and VITEK®2 in the identification of P. aeruginosa.
Kinetics of enzymatic mercury methylation at nanomolar concentrations catalyzed by HgcAB
Authors: Date Swapneeta S. , Parks Jerry M. , Rush Katherine W. , Wall Judy D. , Ragsdale Stephen W. , Johs Alexander
Published: January 2019

Methylmercury (MeHg) is a potent neurotoxin that bioaccumulates in fish. MeHg is generated by anaerobic bacteria and archaea possessing the gene pair hgcAB. Although bacterial mercury (Hg) methylation has been characterized in vivo, the specific role of HgcAB in catalyzing Hg methylation is not well understood. Here we report the kinetics of HgcAB-mediated Hg methylation in cell lysates of Desulfovibrio desulfuricans ND132 at nanomolar Hg concentrations. The enzymatic Hg methylation mediated by HgcAB is highly oxygen-sensitive, irreversible, and follows Michaelis-Menten kinetics with an apparent KM of 3.2 nM and Vmax of 19.7 fmol·min-1·mg-1 total protein for the substrate Hg(II). Although the abundance of HgcAB in the cell lysates is extremely low, Hg(II) was quantitatively converted to MeHg at subnanomolar substrate concentrations. Supplementation with ATP, methyltetrahydrofolate, or pyruvate did not enhance MeHg production under the experimental conditions. Insight into the kinetics of Hg methylation catalyzed by HgcAB advances our understanding of the complex global Hg cycle.
Tombusvirusp19 captures RNase III-cleaved double-stranded RNAs formed by overlapping sense and antisense transcripts inE. coli
Authors: Huang Linfeng , Deighan Padraig , Jin Jingmin , Li Yingxue , Lee Elaine , Mo Shirley S. , Hoover Heather , Abubucker Sahar , Finkel Nancy , McReynolds Larry , Hochschild Ann , Lieberman Judy
Published: January 2019

Antisense transcription is widespread in bacteria. By base pairing with overlapping sense RNAs, antisense RNAs (asRNA) can form long double-stranded RNAs (dsRNA), which are cleaved by RNase III, a dsRNA endoribonuclease. Ectopic expression of plant tombusvirus p19 inE. colistabilizes ~21 bp dsRNA RNase III decay intermediates, which enabled us to characterize otherwise highly unstable asRNA by deep sequencing of p19-captured dsRNA and total RNA. dsRNA formed at most bacterial genes in the bacterial chromosome and in a plasmid. The most abundant dsRNA clusters were mostly formed by divergent transcription of sense and antisense transcripts overlapping at their 5’-ends. The most abundant clusters included small RNAs, such asryeA/ryeB, 4 toxin-antitoxin genes, and 3 tRNAs, and some longer coding genes, includingrsdandcspD. The sense and antisense transcripts in abundant dsRNA clusters were more plentiful and had longer half-lives in RNase III mutant strains, suggesting that formation of dsRNAs promoted RNA decay at these loci. However, widespread changes in protein levels did not occur in RNase III mutant bacteria. Nonetheless, some proteins involved in antioxidant responses and glycolysis changed reproducibly. dsRNAs accumulated in bacterial cells lacking RNase III, increasing in stationary phase, and correlated with increased cell death in RNase III mutant bacteria in late stationary phase. The physiological importance of widespread antisense transcription in bacteria remains unclear but it may become important during environmental stress. Ectopic expression of p19 is a sensitive method for identifying antisense transcripts and RNase III cleavage sites in bacteria.
Avian ANP32B does not support influenza A virus polymerase and influenza A virus relies exclusively on ANP32A in chicken cells
Authors: Long Jason S. , Idoko-Akoh Alewo , Mistry Bhakti , Goldhill Daniel H. , Staller Ecco , Schreyer Jocelyn , Ross Craig , Goodbourn Steve , Shelton Holly , Skinner Michael A. , Sang Helen M. , McGrew Mike J. , Barclay Wendy S.
Published: January 2019

Influenza A viruses (IAV) are subject to species barriers that prevent frequent zoonotic transmission and pandemics. One of these barriers is the poor activity of avian IAV polymerases in human cells. Differences between avian and mammalian ANP32 proteins underlie this host range barrier. Human ANP32A and ANP32B homologues both support function of human-adapted influenza polymerase but do not support efficient activity of avian IAV polymerase which requires avian ANP32A. We show here that avian ANP32B is evolutionarily distinct from mammalian ANP32B, and that chicken ANP32B does not support IAV polymerase activity even of human-adapted viruses. Consequently, IAV does not replicate in chicken cells that lack ANP32A. Amino acid differences in LRR5 domain accounted for the inactivity of chicken ANP32B. Transfer of these residues to chicken ANP32A abolished support of IAV polymerase. Understanding ANP32 function will help develop antiviral strategies and aid the design of influenza virus resistant genome edited chickens.
Characterizing gene tree conflict in plastome-inferred phylogenies
Authors: Walker Joseph F. , Stull Gregory W. , Walker-Hale Nathanael , Vargas Oscar M. , Larson Drew A.
Published: January 2019

Premise of the study

Evolutionary relationships among plants have been inferred primarily using chloroplast data. To date, no study has comprehensively examined the plastome for gene tree conflict.

Methods

Using a broad sampling of angiosperm plastomes, we characterized gene tree conflict among plastid genes at various time scales and explore correlates to conflict (e.g., evolutionary rate, gene length, molecule type).

Key results

We uncover notable gene tree conflict against a backdrop of largely uninformative genes. We find gene length is the strongest correlate to concordance, and that nucleotides outperform amino acids. Of the most commonly used markers, matK greatly outperforms rbcL; however, the rarely used gene rpoC2 is the top-performing gene in every analysis. We find that rpoC2 reconstructs angiosperm phylogeny as well as the entire concatenated set of protein-coding chloroplast genes.

Conclusions

Our results suggest that longer genes are superior for phylogeny reconstruction. The alleviation of some conflict through the use of nucleotides suggests that systematic error is likely the root of most of the observed conflict, but further research on biological conflict within plastome is warranted given the documented cases of heteroplasmic recombination. We suggest rpoC2 as a useful marker for reconstructing angiosperm phylogeny, reducing the effort and expense of assembling and analyzing entire plastomes.
Rtn4a promotes exocytosis in mammalian cells while ER morphology does not necessarily affect exocytosis and translation
Authors: Mukherjee Richik Nilay , Zhang Zhaojie , Levy Daniel L.
Published: January 2019

ER tubules and sheets conventionally correspond to smooth and rough ER, respectively. The ratio of ER tubules-to-sheets varies in different cell types and changes in response to cellular conditions, potentially impacting the functional output of the ER. To directly test if ER morphology impacts ER function, we increased the tubule-to-sheet ratio by Rtn4a overexpression and monitored effects on protein translation and trafficking. While expression levels of several cell surface and secreted proteins were unchanged, their exocytosis was increased. Rtn4a depletion reduced cell surface trafficking without affecting ER morphology, and increasing the tubule-to-sheet ratio by other means did not affect trafficking. These data suggest that Rtn4a enhances exocytosis independently of changes in ER morphology. We demonstrate that Rtn4a enhances ER-to-Golgi trafficking and co-localizes with COPII vesicles. We propose that Rtn4a promotes COPII vesicle formation by inducing membrane curvature. Taken together, we show that altering ER morphology does not necessarily affect protein synthesis or trafficking, but that Rtn4a specifically enhances exocytosis.
TMEM98 is a negative regulator of FRAT mediated Wnt/β-catenin signalling
Authors: van der Wal Tanne , Lambooij Jan-Paul , van Amerongen Renée
Published: January 2019

Wnt/β-catenin signalling is crucial for maintaining the balance between cell proliferation and differentiation, both during tissue morphogenesis and during tissue maintenance in postnatal life. Whereas the signalling activities of the core Wnt/β-catenin pathway components are understood in great detail, far less is known about the precise role and regulation of the many different modulators of Wnt/β-catenin signalling that have been identified to date.

Here we describe TMEM98, a putative transmembrane protein of unknown function, as an interaction partner and regulator of the GSK3-binding protein FRAT2. We show that TMEM98 reduces FRAT2 protein levels and, accordingly, inhibits the FRAT2-mediated induction of β-catenin/TCF signalling. We also characterize the intracellular trafficking of TMEM98 in more detail and show that it is recycled between the plasma membrane and the Golgi. Together, our findings not only reveal a new layer of regulation for Wnt/β-catenin signalling, but also a new biological activity for TMEM98.
A pitfall for machine learning methods aiming to predict across cell types
Authors: Schreiber Jacob , Singh Ritambhara , Bilmes Jeffrey , Noble William Stafford
Published: January 2019

Machine learning models used to predict phenomena such as gene expression, enhancer activity, transcription factor binding, or chromatin conformation are most useful when they can generalize to make accurate predictions across cell types. In this situation, a natural strategy is to train the model on experimental data from some cell types and evaluate performance on one or more held-out cell types. In this work, we show that when the training set contains examples derived from the same genomic loci across multiple cell types, the resulting model can be susceptible to a particular form of bias related to memorizing the average activity associated with each genomic locus. Consequently, the trained model may appear to perform well when evaluated on the genomic loci that it was trained on but tends to perform poorly on loci that it was not trained on. We demonstrate this phenomenon by using epigenomic measurements and nucleotide sequence to predict gene expression and chromatin domain boundaries, and we suggest methods to diagnose and avoid the pitfall. We anticipate that, as more data and computing resources become available, future projects will increasingly risk suffering from this issue.
The Replication-Competent HIV-1 Latent Reservoir is Primarily Established Near the Time of Therapy Initiation
Authors: Abrahams Melissa-Rose , Joseph Sarah B. , Garrett Nigel , Tyers Lynn , Moeser Matthew , Archin Nancie , Council Olivia D. , Matten David , Zhou Shuntai , Doolabh Deelan , Anthony Colin , Goonetilleke Nilu , Karim Salim Abdool , Margolis David M. , Pond Sergei Kosakovsky , Williamson Carolyn , Swanstrom Ronald
Published: January 2019

Although antiretroviral therapy (ART) is highly effective at suppressing HIV-1 replication, the virus persists as a latent reservoir in resting CD4+ T cells during therapy. Little is known about the dynamics of reservoir formation and this reservoir forms even when ART is initiated early after infection. The reservoir of individuals who initiate therapy in chronic infection is generally larger and genetically more diverse than that of individuals who initiate in acute infection, suggesting the reservoir is formed continuously throughout untreated infection. To determine when viruses enter the latent reservoir, we compared sequences of replication-competent viruses from resting CD4+ T cells from nine women on therapy to viral sequences circulating in blood collected longitudinally prior to therapy. We found that 78% of viruses from the latent reservoir were most genetically similar to viruses replicating just prior to therapy initiation. This proportion is far greater than expected if the reservoir forms continuously and is always long-lived. Thus, therapy alters the host environment in a way that allows the formation of a majority of the long-lived latent HIV-1 reservoir.

One Sentence Summary

Most of the long-lived, replication-competent HIV-1 reservoir is formed at the time of therapy initiation.
The Role of the Wnt/PCP Formin Daam1 in Renal Ciliogenesis
Authors: Corkins Mark E. , Krneta-Stankic Vanja , Kloc Malgorzata , McCrea Pierre D. , Gladden Andrew B. , Miller Rachel K.
Published: January 2019

Kidneys are composed of numerous ciliated epithelial tubules called nephrons. Each nephron functions to reabsorb nutrients and concentrate waste products into urine. Defects in primary cilia are associated with abnormal formation of nephrons and cyst formation in a wide range of kidney disorders. Previous work inXenopus laevisand zebrafish embryos established that loss of components that make up the Wnt/PCP pathway, Daam1 and ArhGEF19 (wGEF) perturb kidney tubulogenesis. Dishevelled, which activates both the canonical and non-canonical Wnt/PCP pathway, affect cilia formation in multiciliated cells. In this study, we investigated the role of the noncanoncial Wnt/PCP components Daam1 and ArhGEF19 (wGEF) in renal ciliogenesis utilizing polarized mammalian kidney epithelia cells (MDCKII and IMCD3) andXenopus laevisembryonic kidney. We demonstrate that knockdown of Daam1 and ArhGEF19 in MDCKII and IMCD3 cells leads to loss of cilia, and Daam1’s effect on ciliogenesis is mediated by the formin-activity of Daam1. Moreover, Daam1 co-localizes with the ciliary transport protein IFT88. Interestingly, knocking down Daam1 inXenopuskidney does not lead to loss of cilia. This data suggests a new role for Daam1 in the formation of primary cilia.
The End of Innocence: Open Justice, Free Speech and Privacy in the Modern Constitution – Khuja (formerly PNM) v Times Newspapers Limited
Authors: Craig Robert
Published: January 2019

This case note explores the issue of open justice considered by Khuja (formerly PNM) v Times Newspapers Limited in the Supreme Court and argues that the current law is confused and incoherent. Far from settling the debate, it is suggested that the decision further undermines some of the key assumptions underpinning the current approach, especially in the light of the compelling and humane minority judgment. This leaves the area ripe for reconsideration in general terms. This note challenges many of the formulaic slogans and rhetoric in previous case law as well as suggesting that the meaning of open justice has been lost in current discourse. After summarising the facts, this note sets out the majority and minority judgments, before analysing some of the conceptual difficulties raised – particularly those of open justice, privacy, presumption of innocence and freedom of speech.
Marr v Collie: The Ballooning of the Common Intention Constructive Trust
Authors: Georgiou Alexander Y.S.
Published: January 2019

The decision in Marr v Collie represents a significant expansion of the common intention constructive trust doctrine. Unsupported by authority, it relaxes the requirement that the property be acquired for a ‘domestic’ purpose, and widens the doctrine to encompass all property, whether real or personal. The decision's abrogation of the ‘purpose’ restriction redraws the line between the common intention constructive trust doctrine and the presumed resulting trust doctrine and expands the former to the greatest possible extent. This exacerbates a doctrine already apt to adversely affect both individual litigants and the justice system as a whole, and which creates incongruous theoretical divisions within the law of intentionally created trusts. As the doctrine is reliant on the proposition, unsupported by authority or legislation, that conveyance of a title to land into joint names necessarily gives rise to a trust, it is hoped that a future apex court will reconsider the doctrine's proper scope.
896. ERIGERON GLAUCUS
Authors: Hind Nicholas
Published: January 2019

Erigeron glaucus Ker Gawl. (Compositae: Astereae: Conyzinae) is described and illustrated and its discovery and surrounding history discussed, accompanied by statements on distribution, habitat, phenology, etymology and vernacular names, together with a selection of references where the species has been illustrated. The range of named selections is discussed, and their supposed colours, availability in the horticultural trade, together with comments on cultivation, hardiness, propagation, pests and diseases and uses provided. A statement on its conservation status is made, and other items of interest are inserted.
The Value of Green Water Management in Sub‐Saharan Africa: A Review
Authors: Mafuta Clever
Published: January 2019

Due to its multiple uses, water is a highly competed‐for resource. While the competition is mainly in the use of the resource, contestation over water resources is also demonstrated through how the resource is defined and described. Terms such as water stress and water scarcity are commonly used in literature, and so are various colors that define water quality, including white, grey, yellow, and black water. Water that is useful for agriculture is distinctly known as blue or green water, with the latter increasingly gaining prominence in water planning for improved agricultural productivity. Proper management of green water has been shown to improve grain yields in Sub‐Saharan Africa by as much as 2.5 – 6 times. The arid nature of Sub‐Saharan Africa, coupled with the high evapotranspiration rates, calls for improved management of green water, including reducing evaporation losses, reducing seepage, and increasing the water holding capacity of soils. The value of green water management in Sub‐Saharan Africa is further enhanced by its low‐cost nature when compared to irrigation, which is an area that Sub‐Saharan Africa has also been focusing on as part of the solutions to the increasing food needs of its growing population. Infrastructure for irrigation is costly and not affordable to the majority in Africa. In addition, irrigation can only benefit those communities near the water sources, whereas proper green water management can have benefits to all communities, including those far from a water source.
Water Trading: Innovations, Modeling Prices, Data Concerns
Authors: Colby Bonnie , Isaaks Rowan
Published: January 2019

This article examines policy innovations and data concerns related to water trading in Colorado, and develops econometric models of transactions occurring over two distinct time periods. The Punctuated Equilibrium Theory (PET) of policy adaptation is used to examine shifts in Colorado water trading policy paradigms. Creating better policy frameworks for water trading is a key concern for agricultural, urban, and environmental water interests, given hotter temperatures and more variable precipitation patterns in the western U.S. Contractual arrangements of varying types are being used to engage farmers in providing reliable water supplies for ecosystem and urban needs through changes in farm water use practices. While various pieces of information about changes in water use can be gleaned from public databases, transaction price information is notably lacking. Recent Colorado policy innovations related to water trading emphasize reducing on‐farm consumptive use and making water available for other purposes without permanently drying up irrigated cropland. The use of econometric models analyzing water rights transactions provides insight into how changes in key external factors affect transaction prices. The econometric models developed here focus upon Colorado’s urbanizing Front Range and examine the effect of demographics, housing prices, drought indicators, and agricultural profitability on prices at which water is traded. Volume traded, drought measures, housing prices, alfalfa prices, and water source characteristics are statistically significant in these models. The article concludes by discussing factors that contribute to water trading policy innovations and the broader relevance of Colorado’s innovative trading arrangements to water management challenges in arid regions.
Plant hormone effects on isoprene emission from tropical tree in Ficus septica
Authors: Parveen Shahanaz , Iqbal Md. Asif , Mutanda Ishmael , Rashid Md. Harun‐Ur‐ , Inafuku Masashi , Oku Hirosuke
Published: January 2019

Plant hormones and the circadian rhythm have been implicated in coordinated control of isoprene emission in plants. To gain insights into the signalling networks, foliar application of plant hormones was conducted in a native emitter, Ficus septica. Spraying of 50 μM jasmonic acid (JA) gradually decreased isoprene emission by 88% compared with initial levels within 5 days, and emission increased after relief from JA application. We further explored the molecular regulatory mechanism of isoprene emission by analysing photosynthetic rate, gene expression of 2‐C‐methyl‐D‐erythrytol 4‐phosphate (MEP) pathway, hormone signalling and circadian rhythm processes, and metabolite pool sizes of MEP pathway. Results show that isoprene emission strongly correlated with isoprene synthase (IspS) gene expression and IspS protein levels over the period of JA treatment, indicating transcriptional and possible translational modulation of IspS by JA. Application of JA coordinately modulated genes in the auxin, cytokinin (CK), and circadian rhythm signal transduction pathways. Among the transcriptional factors analysed, MYC2 (JA) and LHY (circadian clock) negatively correlated with isoprene emission. Putative cis‐elements predicted on IspS promoter (G‐box for MYC2 and circadian for LHY) supports our proposal that isoprene emission is regulated by coordinated transcriptional modulation of IspS gene by phytohormone and circadian rhythm signalling.
Mobilized peripheral blood stem cell apheresis via Hickman catheter in pediatric patients
Authors: Doberschuetz Nora , Soerensen Jan , Bonig Halvard , Willasch Andre , Rettinger Eva , Pfirrmann Verena , Salzmann‐Manrique Emilia , Schäfer Richard , Klingebiel Thomas , Bader Peter , Jarisch Andrea
Published: January 2019

BACKGROUND

Autologous stem cell transplantation remains an integral treatment tool for certain childhood malignancies. In children, a central venous catheter is typically necessary to provide adequate flow rates for preparative apheresis. In this study, the feasibility and efficiency of collecting CD34+ cells via an indwelling Hickman catheter, preimplanted for chemotherapy, instead of placing an additional temporary central venous catheter was evaluated.

STUDY DESIGN AND METHODS

Forty‐eight pediatric leukaphereses for autologous hematopoietic stem cell transplantation using Spectra Optia MNC, Version 3.0 were reviewed. We compared preimplanted Hickman catheters with a temporary Shaldon catheter, inserted for apheresis. Apheresis was considered successful if a dose of 2 × 106 CD34+ peripheral blood stem cells/kg BW was achieved.

RESULTS

In 43 (89.6%) of the 48 patients, a Hickman catheter was used for leukapheresis. Only 5 patients (10.4%) received a temporary Shaldon catheter. In both groups, apheresis was performed without apparent adverse reactions. The dose of collected CD34+ peripheral blood stem cells was 12.7 × 106 (range, 2.3–70.7 × 106) cells/kg BW in the Hickman group and 16.2 × 106 (range, 3.8–48.4 × 106) cells/kg BW in the Shaldon group, showing no statistically significant difference (p = 0.58). In both groups, the primary endpoint of a minimal CD34+ cell concentration of 2 × 106 cells/kg BW was achieved at a maximum of two leukapheresis sessions. Apheresis efficacy was further confirmed by the collection efficiency of 40.2% in the Hickman group and 27.8% in the Shaldon group (p = 0.32).

CONCLUSION

These data indicate the reliable feasibility and efficacy of mobilized apheresis via an indwelling Hickman catheter. In light of this, the routine insertion of a dialysis catheter for the purpose of leukapheresis should be critically reconsidered.