bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversible ADP-ribosylation of RNA
Authors: Munnur Deeksha , Bartlett Edward , Mikolčević Petra , Kirby Ilsa T , Rack Johannes Gregor Matthias , Mikoč Andreja , Cohen Michael S , Ahel Ivan
Published: April 2019

ADP-ribosylation is a reversible chemical modification catalysed by ADP-ribosyltransferases such as PARPs that utilize nicotinamide adenine dinucleotide (NAD+) as a cofactor to transfer monomer or polymers of ADP-ribose nucleotide onto macromolecular targets such as proteins and DNA. ADP-ribosylation plays an important role in several biological processes such as DNA repair, transcription, chromatin remodelling, host-virus interactions, cellular stress response and many more. Using biochemical methods we identify RNA as a novel target of reversible mono-ADP-ribosylation. We demonstrate that the human PARPs - PARP10, PARP11 and PARP15 as well as a highly diverged PARP homologue TRPT1, ADP-ribosylate phosphorylated ends of RNA. We further reveal that ADP-ribosylation of RNA mediated by PARP10 and TRPT1 can be efficiently reversed by several cellular ADP-ribosylhydrolases (PARG, TARG1, MACROD1, MACROD2 and ARH3), as well as by MACROD-like hydrolases from VEEV and SARS viruses. Finally, we show that TRPT1 and MACROD homologues in bacteria possess activities equivalent to the human proteins. Our data suggest that RNA ADP-ribosylation may represent a widespread and physiologically relevant form of reversible ADP-ribosylation signalling.
SeqTailor: a user-friendly webserver for the extraction of DNA or protein sequences from next-generation sequencing data
Authors: Zhang Peng , Boisson Bertrand , Stenson Peter D , Cooper David N , Casanova Jean-Laurent , Abel Laurent , Itan Yuval
Published: April 2019

Human whole-genome-sequencing reveals about 4 000 000 genomic variants per individual. These data are mostly stored as VCF-format files. Although many variant analysis methods accept VCF as input, many other tools require DNA or protein sequences, particularly for splicing prediction, sequence alignment, phylogenetic analysis, and structure prediction. However, there is no existing webserver capable of extracting DNA/protein sequences for genomic variants from VCF files in a user-friendly and efficient manner. We developed the SeqTailor webserver to bridge this gap, by enabling rapid extraction of (i) DNA sequences around genomic variants, with customizable window sizes and options to annotate the splice sites closest to the variants and to consider the neighboring variants within the window; and (ii) protein sequences encoded by the DNA sequences around genomic variants, with built-in SnpEff annotator and customizable window sizes. SeqTailor supports 11 species, including: human (GRCh37/GRCh38), chimpanzee, mouse, rat, cow, chicken, lizard, zebrafish, fruitfly, Arabidopsis and rice. Standalone programs are provided for command-line-based needs. SeqTailor streamlines the sequence extraction process, and accelerates the analysis of genomic variants with software requiring DNA/protein sequences. It will facilitate the study of genomic variation, by increasing the feasibility of sequence-based analysis and prediction. The SeqTailor webserver is freely available at http://shiva.rockefeller.edu/SeqTailor/.
1989 At Thirty: A Recast Legacy*
Authors: Betts Paul
Published: April 2019

These days 1989 isn't what it used to be. Not so long ago the wildfire revolutions that swept across Eastern Europe during that momentous year were routinely celebrated as the grand victory of liberal democracy over Soviet-style communism. However, recent developments in Poland, Hungary and elsewhere on the continent which in various ways all invoked 1989, either as inspiration or negative foil, behove us to reconsider the effects of that fateful year in Central Europe from a different perspective. The rise of xenophobia, resurgent populist politics on both the Radical Right and the Left, as well as the spread of ‘illiberal democracy’ across Europe, the US and elsewhere have predictably generated great alarm. Plenty of commentary on the comeback of authoritarian anti-liberalism in Central Europe has claimed that we are witnessing a kind of ‘return of the repressed,’ a dangerous repudiation of the golden principles of 1989 three decades after the uprisings. But construing recent developments in Central Europe as simply an anti-1989 backlash does not get us very far, not least because the unrest of 1989 carried within it the seeds of illiberalism as well. With distance, the inheritance of the ‘revolutionary autumn’ appears more mixed and precarious, and much harder to classify than it once was. Like all revolutions, 1989 brought in its train a mixed bag of dreams and disappointments, stark ruptures and stubborn continuities, and this article revisits some of the grey and even darker tones of the inheritance.
Biological Function of Changes in RNA Metabolism in Plant Adaptation to Abiotic Stress
Authors: Matsui Akihiro , Nakaminami Kentaro , Seki Motoaki
Published: April 2019

Plant growth and productivity are greatly impacted by environmental stresses. Therefore, plants have evolved various sophisticated mechanisms for adaptation to nonoptimal environments. Recent studies using RNA metabolism-related mutants have revealed that RNA processing, RNA decay and RNA stability play an important role in regulating gene expression at a post-transcriptional level in response to abiotic stresses. Studies indicate that RNA metabolism is a unified network, and modification of stress adaptation-related transcripts at multiple steps of RNA metabolism is necessary to control abiotic stress-related gene expression. Recent studies have also demonstrated the important role of noncoding RNAs (ncRNAs) in regulating abiotic stress-related gene expression and revealed their involvement in various biological functions through their regulation of DNA methylation, DNA structural modifications, histone modifications and RNA–RNA interactions. ncRNAs regulate mRNA transcription and their synthesis is affected by mRNA processing and degradation. In the present review, recent findings pertaining to the role of the metabolic regulation of mRNAs and ncRNAs in abiotic stress adaptation are summarized and discussed.
The Age of Coumarins in Plant–Microbe Interactions
Authors: Stringlis Ioannis A , de Jonge Ronnie , Pieterse Corn� M J
Published: April 2019

Coumarins are a family of plant-derived secondary metabolites that are produced via the phenylpropanoid pathway. In the past decade, coumarins have emerged as iron-mobilizing compounds that are secreted by plant roots and aid in iron uptake from iron-deprived soils. Members of the coumarin family are found in many plant species. Besides their role in iron uptake, coumarins have been extensively studied for their potential to fight infections in both plants and animals. Coumarin activities range from antimicrobial and antiviral to anticoagulant and anticancer. In recent years, studies in the model plant species tobacco and Arabidopsis have significantly increased our understanding of coumarin biosynthesis, accumulation, secretion, chemical modification and their modes of action against plant pathogens. Here, we review current knowledge on coumarins in different plant species. We focus on simple coumarins and provide an overview on their biosynthesis and role in environmental stress responses, with special attention for the recently discovered semiochemical role of coumarins in aboveground and belowground plant–microbe interactions and the assembly of the root microbiome.
A Randomized Clinical Trial of Group Acupuncture for Painful Diabetic Neuropathy Among Diverse Safety Net Patients
Authors: Chao Maria T , Schillinger Dean , Nguyen Unity , Santana Trilce , Liu Rhianon , Gregorich Steve , Hecht Frederick M
Published: April 2019

Objective

Existing pharmacologic approaches for painful diabetic neuropathy (PDN) are limited in efficacy and have side effects. We examined the feasibility, acceptability, and effects of group acupuncture for PDN.

Design and Setting

We randomized patients with PDN from a public safety net hospital to 1) usual care, 2) usual care plus 12 weeks of group acupuncture once weekly, or 3) usual care plus 12 weeks of group acupuncture twice weekly.

Methods

The primary outcome was change in weekly pain intensity (daily 0–10 numerical rating scale [NRS] averaged over seven days) from baseline to week 12. We also assessed health-related quality of life and related symptoms at baseline and weeks 6, 12, and 18.

Results

We enrolled 40 patients with PDN (baseline pain = 5.3). Among participants randomized to acupuncture, 92% attended at least one treatment (mean treatments = 10.1). We observed no significant differences between once- vs twice-weekly acupuncture and combined those groups for the main analyses. Compared with usual care, participants randomized to acupuncture experienced greater decreases in pain during the 12-week intervention period (between-group differences from baseline = –2.06, 95% confidence interval [CI] = –3.01 to –1.10), but benefits were not maintained after acupuncture ended (baseline to week 18 = –0.61, 95% CI = –1.46 to 0.24). Quality of life improved for acupuncture participants (baseline to week 12 difference = 11.79, 95% CI = 1.92 to 21.66), but group differences were not significant compared with usual care (25.58, 95% CI = –3.90 to 55.06).

Conclusions

Group acupuncture is feasible and acceptable among linguistically and racially diverse safety net patients. Findings suggest clinically relevant reduction in pain from PDN and quality of life improvements associated with acupuncture, with no differences based on frequency.
Medicalised Battlefields: The Evolution of Military Medical Care and the ‘Medic’ in Japan
Authors: Harari Reut
Published: April 2019

During the tumultuous Meiji era (1868–1912), medicine, war and the relationship between them changed significantly in Japan, in reaction to the expansion of western imperialism. During this era of reforms, which coincided with the rise of humanitarianism and the modernisation of international warfare, a new role emerged at the intersection of war and medicine: the medic. Medics were paradoxical figures, serving as soldiers whom the military trained to provide care but forbade to fight. The medic evolved continuously as army leaders and the army’s medical department repeatedly redefined it in light of knowledge obtained from abroad and of accrued wartime experience. This article explores how the role evolved out of discrepancies between learned, planned and encountered realities and argues that the invention and reinvention of the medic mirrored attempts to redefine not only medicine’s role in battle, but also medical care, where it was to be provided and by whom.
‘Solid foundations’: the advantages of using Guernsey Foundations for building a family office
Authors: Davidson Alasdair , Semlitsch Jasmin
Published: April 2019

Family office services are gaining ever-increasing popularity and traction across the global offshore financial centres. The key characteristics and distinctions of Guernsey’s foundation regime make it a particularly effective tool for wealthy individuals and their dedicated family offices to achieve an array of investment, succession planning, or philanthropic objectives. In this article, we explore how Guernsey foundations can cater for the desired levels of control, tailor the rights of beneficiaries, maintain confidentiality, and be used in new and innovative ways to enhance and complement wealth management structures.
Intracellular Demethylation of Methylmercury to Inorganic Mercury by Organomercurial Lyase (MerB) Strengthens Cytotoxicity
Authors: Takanezawa Yasukazu , Nakamura Ryosuke , Matsuda Haruki , Yagi Tomomi , Egawa Zen , Sone Yuka , Uraguchi Shimpei , Adachi Tatsumi , Kiyono Masako
Published: April 2019

Some methylmercury (MeHg) is converted to inorganic mercury (Hg2+) after incorporation into human and animal tissues, where it can remain for a long time. To determine the overall toxicity of MeHg in tissues, studies should evaluate low concentrations of Hg2+. Although demethylation is involved, the participating enzymes or underlying mechanisms are unknown; in addition, the low cell membrane permeability of Hg2+ makes these analyses challenging. We established model cell lines to assess toxicities of low concentrations of Hg2+ using bacterial organomercury lyase (MerB). We engineered MerB-expressing HEK293 and HeLa cell lines that catalyze MeHg demethylation. These cells were significantly more sensitive to MeHg exposure compared to the parental cells. MeHg treatment remarkably induced metallothioneins (MTs) and hemeoxygenase-1 (HMOX-1) mRNAs and modest expression of superoxide dismutase 1, whereas catalase and glutathione peroxidase 1 mRNAs were not up-regulated. merB knockdown using small interfering RNA supported the induction of MT and HMOX-1 mRNA by MerB enzymatic activity. Pretreatment with Trolox, a water-soluble vitamin E analog, did not inhibit MeHg-induced elevation of MT-Ix and HMOX-1 mRNAs in MerB-expressing cells, suggesting that Hg2+ works independently of reactive oxygen species generation. Similar results were obtained in cells expressing MerB, suggesting that high MTs and HMOX-1 induction and cytotoxicity are common cellular responses to low intracellular Hg2+ concentrations. This is the first study to establish cell lines that demethylate intracellular MeHg to Hg2+ using bacterial MerB for overcoming the low membrane permeability of Hg2+ and exploring the intracellular responses and toxicities of low Hg2+ concentrations.
The significance of the qualifying declarations under the Cape Town Convention
Authors: Traschler Thomas
Published: April 2019

This article outlines and critically examines the relationship between the qualifying declarations and the economic advantages of the Cape Town Convention on International Interests in Mobile Equipment. It shows that the qualifying declarations operate rather differently from how they are perceived in academic literature and practice. Specifically, the article shows that the critical advantage of the Convention and the qualifying declaration is the potential to reduce enforcement risk relating to different States in a specific transactional setting and not, as some observers might wrongly perceive, from the Cape Town Discount. Thus, if States are not prepared to make the qualifying declarations, this should not deter them from ratifying the Convention and the Protocol. States and society may benefit from adoption of the Convention and its related protocols with partial—or even without—adoption of the qualifying declarations, bearing in mind of course the interdependency of the Convention’s remedies.
A Remorin from Nicotiana benthamiana Interacts with the Pseudomonas Type-III Effector Protein HopZ1a and is Phosphorylated by the Immune-Related Kinase PBS1
Authors: Albers Philip , Üstün Suayib , Witzel Katja , Kraner Max , Börnke Frederik
Published: April 2019

The plasma membrane (PM) is at the interface of plant–pathogen interactions and, thus, many bacterial type-III effector (T3E) proteins target membrane-associated processes to interfere with immunity. The Pseudomonas syringae T3E HopZ1a is a host cell PM-localized effector protein that has several immunity-associated host targets but also activates effector-triggered immunity in resistant backgrounds. Although HopZ1a has been shown to interfere with early defense signaling at the PM, no dedicated PM-associated HopZ1a target protein has been identified until now. Here, we show that HopZ1a interacts with the PM-associated remorin protein NbREM4 from Nicotiana benthamiana in several independent assays. NbREM4 relocalizes to membrane nanodomains after treatment with the bacterial elicitor flg22 and transient overexpression of NbREM4 in N. benthamiana induces the expression of a subset of defense-related genes. We can further show that NbREM4 interacts with the immune-related receptor-like cytoplasmic kinase avrPphB-susceptible 1 (PBS1) and is phosphorylated by PBS1 on several residues in vitro. Thus, we conclude that NbREM4 is associated with early defense signaling at the PM. The possible relevance of the HopZ1a–NbREM4 interaction for HopZ1a virulence and avirulence functions is discussed.

[Formula: see text]Copyright © 2019 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Identification and Characterization of the Core Rice Seed Microbiome
Authors: Eyre Alexander W. , Wang Mengying , Oh Yeonyee , Dean Ralph A.
Published: April 2019

The use of microbes in agriculture for enhancing crop production is an emerging alternative to chemical fertilizers and pesticides; however, their effectiveness is often limited by factors such as host genotype and variability in geographic location. To address this issue, the microbiomes of six different rice (Oryza sativa) seeds, sourced from two locations in Arkansas, U.S.A. of two different genotypes and two harvest years, were characterized. The bacterial and fungal communities were identified in each of four seed compartments (grain, outer grain, husk, and outer husk) using high throughput Illumina MiSeq sequencing. More unique amplicon sequence variants were identified in the outer seed husk and least in the grain compartment for both the fungal and bacterial microbiomes, however this only resulted in a decrease in diversity for the fungal communities. Principal component analysis indicated that each tissue compartment harbored relatively distinct bacterial and fungal communities for the three innermost compartments. A bacterial and fungal core microbiome shared among the six seed types for each compartment was identified. Key bacterial genera in the core across all compartments were Sphingomonas, Methylobacterium, and taxa in the family Enterobacteriaceae, members of which have been reported to support rice growth. Compared with the bacterial core, more fungal taxa were identified, possibly resulting from the more abundant reads after filtering, and key genera identified were Alternaria, Hannaella, and members of the order Pleosporales. These core members represent valuable candidates for manipulating the rice microbiome, decreasing the use of chemicals while increasing plant performance.
TAPAS: A Thresholding Approach for Probability Map Automatic Segmentation in Multiple Sclerosis
Authors: Valcarcel Alessandra M. , Muschelli John , Pham Dzung L. , Martin Melissa Lynne , Yushkevich Paul , Calabresi Peter A. , Bakshi Rohit , Shinohara Russell T.
Published: April 2019

Total brain white matter lesion (WML) volume is the most widely established magnetic resonance imaging (MRI) outcome measure in studies of multiple sclerosis (MS). To estimate WML volume, there are a number of automatic segmentation methods, yet, manual delineation remains the gold standard approach. These approaches often yield a probability map to which a threshold is applied to create lesion segmentation masks. Unfortunately, few approaches systematically determine the threshold employed; many methods use a manually selected threshold, thus introducing human error and bias into the automated procedure. In this study, we propose and validate an automatic thresholding algorithm, Thresholding Approach for Probability Map Automatic Segmentation in Multiple Sclerosis (TAPAS), to obtain subject-specific threshold estimates for probability map automatic segmentation of T2-weighted (T2) hyperintense WMLs. Using multimodal MRI, the proposed method applies an automatic segmentation algorithm to obtain probability maps. We obtain the true subject-specific threshold that maximizes Sørensen-Dice Similarity Coefficient (DSC). Then the subject-specific thresholds are modeled on a naive estimate of volume using a general additive model. Applying this model, we predict a subject-specific threshold in data not used for training. We ran a Monte Carlo-resampled split-sample cross-validation (100 validation sets) using two data sets: the first obtained from the Johns Hopkins Hospital (JHH) on a Philips 3 Tesla (3T) scanner (n = 94) and a second collected at the Brigham and Women’s Hospital (BWH) using a Siemens 3T scanner (n = 40). By means of the proposed automated technique, in the JHH data, we found an average reduction in subject-level absolute error of 0.1 mL per one mL increase in manual volume. Using Bland-Altman analysis, we found that volumetric bias associated with group-level thresholding is mitigated when applying TAPAS. The BWH data showed similar absolute error estimates using group-level thresholding or TAPAS likely since Bland-Altman analyses indicate no systematic biases associated with group or TAPAS volume estimates. The current study presents the first validated fully automated method for subject-specific threshold prediction to segment brain lesions.
Quantitative proteomics identifies novel PIAS1 substrates involved in cell migration and motility
Authors: Li Chongyang , McManus Francis P. , Plutoni Cédric , Pascariu Cristina Mirela , Nelson Trent , Delsin Lara Elis Alberici , Emery Gregory , Thibault Pierre
Published: April 2019

The Protein Inhibitor of Activated STAT 1 (PIAS1) is an E3 SUMO ligase that plays important roles in various cellular pathways, including STAT signaling, p53 pathway, and the steroid hormone signaling pathway. PIAS1 can SUMOylate PML (at Lys-65 and Lys-160) and PML-RARα promoting their ubiquitin-mediated degradation. Increasing evidence shows that PIAS1 is overexpressed in various human malignancies, including prostate and lung cancers. To understand the mechanism of action of PIAS1, we developed a quantitative SUMO proteomic approach to identify potential substrates of PIAS1 in a system-wide manner. Our analyses enabled the profiling of 983 SUMO sites on 544 proteins, of which 204 SUMO sites on 123 proteins were identified as putative PIAS1 substrates. These substrates are involved in different cellular processes, such as transcriptional regulation, DNA binding and cytoskeleton dynamics. Further functional studies on Vimentin (VIM), a type III intermediate filament protein involved in cytoskeleton organization and cell motility, revealed that PIAS1 exerts its effects on cell migration and cell invasion through the SUMOylation of VIM at Lys-439 and Lys-445 residues. VIM SUMOylation was necessary for its dynamic disassembly, and cells expressing a non-SUMOylatable VIM mutant showed reduced levels of proliferation and migration. Our approach not only provides a novel strategy for the identification of E3 SUMO ligase substrates, but also yields valuable biological insights into the unsuspected role of PIAS1 and VIM SUMOylation on cell motility.
Cell-type and endocannabinoid specific synapse connectivity in the adult nucleus accumbens core
Authors: Deroche Marion A. , Lassalle Olivier , Manzoni Olivier J.
Published: April 2019

The nucleus accumbens (NAc) is a mesocorticolimbic structure that integrates cognitive, emotional and motor functions. Although its role in psychiatric disorders is widely acknowledged, the understanding of its circuitry is not complete. Here we combined optogenetic and whole-cell recordings to draw a functional portrait of excitatory disambiguated synapses onto D1 and D2 medium spiny neurons (MSNs) in the adult mouse NAc core. Comparing synaptic properties of ventral hippocampus (vHipp), basolateral amygdala (BLA) and prefrontal cortex (PFC) inputs revealed a hierarchy of synaptic inputs and feedforward inhibition that depends on the identity of the postsynaptic target MSN. Thus, the BLA is the dominant excitatory pathway onto D1 MSNs (BLA > PFC = vHipp) while PFC inputs dominate D2 MSNs (PFC > vHipp > BLA). Feedforward inhibition of MSN firing too, was input and cell-type specific: while minimal at vHipp-D1 and vHipp-D2 inputs; it inhibited with similar efficacy BLA-D1 or BLA-D2 inputs, was minimal at PFC-D1 but maximal at PFC-D2 inputs. We also tested the hypothesis that endocannabinoids endow excitatory circuits with pathway- and cell-specific plasticity. Thus, while CB1 receptors (CB1R) uniformly depress excitatory pathways irrespective of MSNs identity, TRPV1 receptors (TRPV1R) bidirectionally control inputs onto the NAc core in a pathway-specific manner. Finally, we show how the interplay of TRPV1R/CB1R shapes plasticity at identified BLA-NAc synapses. Together these data shed new light on synapse and circuit specificity in the adult NAc core and illustrate how endocannabinoids contribute to pathway-specific synaptic plasticity.

SIGNIFICANCE STATEMENT

We examined the impact of connections from the ventral hippocampus (vHipp,) basolateral amygdala (BLA) and prefrontal cortex (PFC) onto identified medium spiny neurons (MSN) in the adult accumbens core. We found BLA inputs were strongest at D1 MSNs while PFC inputs dominate D2 MSNs. We evaluated the role of the endocannabinoid system in pathway- and cell-specific plasticity and found that CB1 receptors (CB1R) and TRPV1 receptors (TRPV1R) bidirectionally control synaptic transmission and plasticity onto accumbens’ MSNs in a pathway- and cell-specific manner. Finally, we clarify how the interplay of TRPV1R/CB1R shapes plasticity at identified BLA-NAc synapses.
Preparation of PLGA Nanoparticles Encapsulated with Fluorescent Probe Coumarin-6
Authors: Purr Elizebeth , Marshall Jacob , Smith John
Published: April 2019

In this report, we provided a novel platform to prepare fluorescent probe coumarin-6 nanoparticles by using biodegradable material polylactic acid-glycolic acid copolymer (PLGA) as material. The coumarin-6-PLGA nanoparticles were prepared by double emulsion and solvent evaporation. The encapsulation efficiency and releasing kinetics were also investigated. Results indicate that the encapsulation efficiency of coumarin-6 nanoparticles was 51.6%, the utilization rate was 81.9%, the average particle size was 135 nm, and the leakage rate of coumarin-6 in vitro was lower than 72 h. 2%. Our experimental results provide evidence that PLGA nanoparticles can effectively encapsulate fluorescent probe Coumarin-6 and release the probe in a controlled manner.
IMAGE: High-powered detection of genetic effects on DNA methylation using integrated methylation QTL mapping and allele-specific analysis
Authors: Fan Yue , Vilgalys Tauras P. , Sun Shiquan , Peng Qinke , Tung Jenny , Zhou Xiang
Published: April 2019

Identifying genetic variants that are associated with methylation variation – an analysis commonly referred to as methylation quantitative trait locus (mQTL) mapping -- is important for understanding the epigenetic mechanisms underlying genotype-trait associations. Here, we develop a statistical method, IMAGE, for mQTL mapping in sequencing-based methylation studies. IMAGE properly accounts for the count nature of bisulfite sequencing data and incorporates allele-specific methylation patterns from heterozygous individuals to enable more powerful mQTL discovery. We compare IMAGE with existing approaches through extensive simulation. We also apply IMAGE to analyze two bisulfite sequencing studies, in which IMAGE identifies more mQTL than existing approaches.
Rho-kinase planar polarisation at tissue boundaries depends on phospho-regulation of membrane residence time
Authors: Sidor Clara , Stevens Tim J. , Jin Li , Boulanger Jérôme , Röper Katja
Published: April 2019

Rho-kinase (Rok) is a major myosin II activator during morphogenesis. In theDrosophilaembryonic salivary gland placode Rok is planar polarised at the tissue boundary, through a negative regulation by the apical polarity protein Crumbs that is anisotropically localised at the boundary. However, in inner cells of the placode both Crumbs and Rok are isotropically enriched at junctions. We propose a model that reconciles both behaviours through modulation of Rok membrane residence time by Crumbs and downstream effectors. Using FRAP in embryos expressing endogenously-tagged Rok combined within silicosimulations, we find that the lower membrane dissociation rate (koff) of Rok at the tissue boundary, where Crumbs membrane levels are lower, explains this boundary-specific effect. The S/T-kinase Pak1 negatively affects Rok membrane associationin vivowithin the epidermis, andin vitrocan phosphorylate Rok near the PH domain that mediates membrane association. Pak1 is recruited to the membrane by Cdc42 which, like its binding partner Crumbs, shows anisotropic localisation at the boundary. These data reveal an important mechanism of modulation of Rok membrane residence time via affecting the koffthat may be widely employed during tissue morphogenesis.
Phylogenomics of Selaginellaceae with special reference to the enigmatic sanguinolenta group
Authors: Zhang Hong-Rui , Wei Ran , Xiang Qiao-Ping , Zhang Xian-Chun
Published: April 2019

Selaginellaceae has been repeatedly proved as monophyly by previous studies with only one genus being recognized. However, the subgeneric classification has been debated during the recent decades. Furthermore, phylogenetic position of the newly identified sanguinolenta group has not been resolved, varying depending on the datasets and analysis methods. We carried out the phylogenomic analyses of twenty-six species from Selaginellaceae with ten species being newly sequenced and three species representing the sanguinolenta group. Four of the ten newly sequenced plastomes are assembled into the complete molecules, whereas the other six species are only assembled into five to sixteen contigs owing to high numbers of repeats. The phylogenetic framework from our study is basically congruent with the subgeneric classification of Weststrand and Korall (2016b). The position of sanguinolenta group was resolved as the basal clade in subg. Stachygynandrum, which support the position β proposed by Weststrand and Korall (2016a), also supported by the morphological characters of dimorphic vegetative leaves, monomorphic sporophylls and intermixed sporangial arrangements. Both values of dS, dN and GC content in Selaginellaceae plastomes were significantly higher than those of other lycophytes (Isoetaceae and Lycopodiaceae). The correlation analysis showed that the elevated synonymous substitution rate was significantly correlated with the high GC content in Selaginellaceae. Besides, the values of dS and dN differs significantly between branches in the phylogenetic tree of Selaginellaceae. We propose that both high GC content and the extensive RNA editing sites contributed to the elevated substitution rate in Selaginellaceae, and all of these three factors could influence the stability of phylogenetic topology of Selaginellaceae.
Two Y chromosome-encoded genes determine sex in kiwifruit
Authors: Akagi Takashi , Pilkington Sarah M. , Varkonyi-Gasic Erika , Henry Isabelle M. , Sugano Shigeo S. , Sonoda Minori , Firl Alana , McNeilage Mark A. , Douglas Mikaela J. , Wang Tianchi , Rebstock Ria , Voogd Charlotte , Datson Paul , Allan Andrew C. , Beppu Kenji , Kataoka Ikuo , Tao Ryutaro
Published: April 2019

Dioecy, the presence of male and female individuals, has evolved independently in multiple flowering plant lineages. Although theoretical models for the evolution of dioecy, such as the “two-mutation” model, are well established, little is known about the specific genes determining sex and their evolutionary history. Kiwifruit, a major tree crop consumed worldwide, is a dioecious species. In kiwifruit, we had previously identified a Y-encoded sex-determinant candidate gene acting as the suppressor of feminization (SuF), named Shy Girl (SyGI). Here, we identified a second Y-encoded sex-determinant that we named Friendly boy (FrBy), which exhibits strong expression in tapetal cells. Gene-editing and complementation analyses in Arabidopsis thaliana and Nicotiana tabacum indicated that FrBy acts for the maintenance of male (M) functions, independently of SyGI, and that these functions are conserved across angiosperm species. We further characterized the genomic architecture of the small (< 1 Mb) male specific region of the Y-chromosome (MSY), which harbors only two genes significantly expressed in developing gynoecia and androecia, respectively: SyGI and FrBy. Resequencing of the genome of a natural hermaphrodite kiwifruit revealed that this individual is genetically male but carries deletion(s) of parts of the Y-chromosome, including SyGI. Additionally, expression of FrBy in female kiwifruit resulted in hermaphrodite plants. These results clearly indicate that Y-encoded SyGI and FrBy act independently as the SuF and M factors in kiwifruit, respectively, and provide insight into the evolutionary path leading to a two-factor sex determination system but also a new breeding approach for dioecious species.
A genetic selection reveals functional metastable structures embedded in a toxin-encoding mRNA
Authors: Masachis Sara , Tourasse Nicolas J. , Lays Claire , Faucher Marion , Chabas Sandrine , Iost Isabelle , Darfeuille Fabien
Published: April 2019

Post-transcriptional regulation plays important roles to finely tune gene expression in bacteria. In particular, regulation of type I toxin-antitoxin (TA) systems is achieved through sophisticated mechanisms involving toxin mRNA folding. Here, we set up a genetic approach to decipher the molecular underpinnings behind the regulation of a type I TA in Helicobacter pylori. We used the lethality induced by chromosomal inactivation of the antitoxin to select mutations that suppress toxicity. We found that single point mutations are sufficient to allow cell survival. Mutations located either in the 5’ untranslated region or within the open reading frame of the toxin hamper its translation by stabilizing stem-loop structures that sequester the Shine-Dalgarno sequence. We propose that these short hairpins correspond to metastable structures that are transiently formed during transcription to avoid premature toxin expression. This work uncovers the co-transcriptional inhibition of translation as an additional layer of TA regulation in bacteria.
Regenerative growth is constrained bybrain tumorto ensure proper patterning inDrosophila
Authors: Abidi Syeda Nayab Fatima , Hsu Felicity Ting-Yu , Smith-Bolton Rachel K.
Published: April 2019

Some animals respond to injury by inducing new growth to regenerate the lost structures. This regenerative growth must be carefully controlled and constrained to prevent overgrowth and to allow correct organization of the regenerating tissue. However, the factors that restrict regenerative growth have not been identified. Using a genetic ablation system in theDrosophilawing imaginal disc, we have identified one mechanism that constrains regenerative growth, impairment of which also leads to erroneous patterning of the final appendage. Regenerating discs with reduced levels of the RNA-regulator Brain tumor (Brat) exhibit enhanced regeneration, but produce adult wings with disrupted margins that are missing extensive tracts of sensory bristles. In these mutants, aberrantly high expression of the pro-growth factor Myc and its downstream targets likely contributes to this loss of cell-fate specification. Thus, Brat constrains the expression of pro-regeneration genes and ensures that the regenerating tissue forms the proper final structure.

Author Summary

While much has been published about the signals that stimulate regeneration, the mechanisms that constrain and/or terminate regeneration have not been well characterized. Thus, we do not understand what limits may exist on the rate of regenerative growth, what mechanisms constrain regeneration, and what the consequences might be of enhancing regrowth. Here, we detail our discovery and characterization of a mechanism that constrains regeneration, and the deleterious effects of reducing that constraint. In this manuscript, we describe our identification of the RNA regulator Brat as a factor that constrains regenerative growth. Without this constraint on regenerative growth, patterning mistakes occur leading to a malformed regenerated structure. We demonstrate that the patterning errors are not due to faster growth itself, but are due to the overexpression of the pro-growth transcription factor Myc.
Decreased viability and neurite length in neural cells treated with chitosan-dextran sulfate nanocomplexes
Authors: Zamproni Laura N. , Teixeira Daniela , Alliegro Amanda Arnaut , Maugéri Ieda Longo , Rieux Anne des , Porcionatto Marimelia A.
Published: April 2019

CXCL12 is a chemokine known to regulate migration, proliferation, and differentiation of neural stem cells (NSCs) and to play a neuroprotective role in ischemic stroke. Chitosan-dextran sulfate nanocomplexes (Ch/DS NC) are known nanoparticulated systems used to efficiently deliver heparin-binding factors. Here we evaluate Ch/DS NC as carriers for CXCL12 in a mouse model of stroke. Free CXCL12 reduced the size of the ischemic brain lesion. However, when Ch/DS NC were administrated, the stroke volume increased. Neurotoxic screening revealed that Ch/DS NC reduced neuronal viability, decreased the extension of neurites and impaired NSC migration in vitro. To the best of our knowledge, neurotoxicity of Ch/DS NC has not been reported and further screenings will be needed in order to evaluate the biological safety of these nanocomposites. Our results add new data on nanoparticle neurotoxicity and may help us to better understand the complex interactions of the nanostructures with biological components.
Zinc restriction promotes β-cell hyper-hormonemia and endocrine pancreas degeneration in mice
Authors: Sisnande Tháyna , Lima Cleverton K. , da Silva Dayana Cabral , Beninatto Thayana Moulin , Alves Natália Leão , Amaral Mariana J. , Miranda-Alves Leandro , Lima Luís Maurício T. R.
Published: April 2019

Zinc is a key component of proteins, including interaction with varying pancreatic hormones, including insulin and amylin. Zinc is key in insulin crystallinity in ZnT8 knock-out mice models, although the dietary role of zinc restriction over both energetic metabolism and ß-pancreatic hormonemia and morphology remained unexplored. We aimed to test whether dietary zinc restriction on swiss male mice would impact over endocrine pancreas and metabolic phenotype. We evaluated the role of dietary zinc restriction on ß-pancreatic hormonemia on non-transgenic Swiss male mice weaned onto a control or low-zinc diet for 4 weeks. Growth, glycemia, insulinemia, amylinemia and pancreatic islet were smaller in intervention group despite insulin crystallinity in secretory granules. We have found overlabelling for insulin, amylin and toxic oligomers in apoptotic pancreatic islet. High production of β-pancreatic hormones in zinc-restricted animals counteract the decreasing islet size due to their apoptotic cells. We conclude that zinc deficiency is sufficient to promote islet β-cell hormonal disruption and degeneration.
Can fallopian tube anatomy predict pregnancy and pregnancy outcomes after tubal reversal surgery?
Authors: de Souza Rafael S. , Berger Gary S.
Published: April 2019

We conducted this study to determine if postoperative fallopian tube anatomy can predict the likelihood of pregnancy and pregnancy outcomes after tubal sterilisation reversal.

We built a flexible, non-parametric, multivariate model via generalised additive models to assess the effects of these tubal parameters observed during tubal reparative surgery: tubal lengths; differences in tubal segment location and diameters at the anastomosis sites; and, fibrosis of the tubal muscularis.

Age and tubal length (in that order) are the primary features determining the likelihood of pregnancy. For pregnancy outcomes, age is the primary predictor of miscarriage, but tubal length is the most influential predictor of the odds of birth and ectopic pregnancy. Segment location and diameters contribute slightly to the odds of miscarriage and ectopic pregnancy, whereas fibrosis has little apparent effect.

This study is the first to show that a statistical learning predictive model based on fallopian tube anatomy can predict both pregnancy and pregnancy outcome probabilities after tubal reversal surgery.
Metabolic Perceptrons for Neural Computing in Biological Systems
Authors: Pandi Amir , Koch Mathilde , Voyvodic Peter L , Soudier Paul , Bonnet Jerome , Kushwaha Manish , Faulon Jean-Loup
Published: April 2019

Abstract

Synthetic biological circuits are promising tools for developing sophisticated systems for medical, industrial, and environmental applications. So far, circuit implementations commonly rely on gene expression regulation for information processing using digital logic. Here, we present a new approach for biological computation through metabolic circuits designed by computer-aided tools, implemented in both whole-cell and cell-free systems. We first combine metabolic transducers to build an analog adder, a device that sums up the concentrations of multiple input metabolites. Next, we build a weighted adder where the contributions of the different metabolites to the sum can be adjusted. Using a computational model trained on experimental data, we finally implement two four-input “perceptrons” for desired binary classification of metabolite combinations by applying model-predicted weights to the metabolic perceptron. The perceptron-mediated neural computing introduced here lays the groundwork for more advanced metabolic circuits for rapid and scalable multiplex sensing.
Prevalence and Determinants of Caesarean Section in South and South-east Asian Women
Authors: Verma Vivek , Vishwakarma Ramesh K. , Nath Dilip C. , Abid Omer , Prakash Ram
Published: April 2019

Background

Caesarean section is considered a preferable and safe method of delivery. In the last decade, its prevalence has increased in both developed and developing countries. In the context of developing countries viz., South Asia (the highest populated region) and South-east Asia (the third highest populated region), the preference for, and variation in, caesarean section delivery and its associated maternal socioeconomic characteristics are still to be determined.

Objective

To study the magnitude of caesarean delivery in the South and South-east Asian countries, by correlating the maternal socioeconomic characteristics with the preference for caesarean sections.

Methodology

Data on ever-married women of nine developing countries of South and South-east Asia viz., Vietnam, India, Maldives, Timor-Leste, Nepal, Indonesia, Pakistan, Bangladesh and Cambodia, from Demographic and Health Survey has considered. Both bivariate and multivariate binary logistic regression models were used to estimate the probability that a woman undergoes caesarean section and to assess the influence of maternal socioeconomic characteristics towards the preference for caesarean section.

Conclusion

In seven urban and four rural regions of nine South and South-East Asian countries, a significant inclination towards the caesarean delivery above the more recent outdate WHO recommended optimal range of 10-15% or the more recent study by top researchers of 19% has been found. The analysis confirmed that the prevalence of caesarean section and its associated maternal socioeconomic characteristics varied widely among these nine South and South-East Asian countries.
Small RNA Mcr11 regulates genes involved in the central metabolism ofMycobacterium tuberculosisand requires 3’ sequence along with the transcription factor AbmR for stable expression
Authors: Girardin Roxie C. , McDonough Kathleen A.
Published: April 2019

Mycobacterium tuberculosis(Mtb), the etiologic agent of tuberculosis, must adapt to host-associated environments during infection by modulating gene expression. Small regulatory RNAs (sRNAs) are key regulators of bacterial gene expression, but their roles in Mtb are not well understood. Here, we address the expression and function of the Mtb sRNA Mcr11, which is associated with slow bacterial growth and latent infections in mice. We found, by using biochemical and genetic approaches, that the AbmR transcription factor and an extended region of native sequence 3’ to themcr11gene enhance production of mature Mcr11. Additionally, we found that expression of Mcr11 was unstable in the saprophyteMycobacterium smegmatis, which lacks anmcr11orthologue. Bioinformatic analyses used to predict regulatory targets of Mcr11 identified 9-11 nucleotide regions immediately upstream of Rv3282 andlipBwith potential for direct base-pairing with Mcr11.mcr11-dependent regulation of Rv3282,lipB,Rv2216 andpknAwas demonstrated using qRT-PCR in wild type versusmcr11-deleted Mtb and found to be responsive to the presence of fatty acids. These studies establish that Mcr11 has roles in regulating growth and central metabolism in Mtb that warrant further investigation. In addition, our finding that multiple factors are required for production of stable, mature Mcr11 emphasizes the need to study mechanisms of sRNA expression and stability in TB complex mycobacteria to understand their roles in TB pathogenesis.

Author Summary

Bacterial pathogens must continuously modulate their gene expression in response to changing conditions to successfully infect and survive within their hosts. Transcription factors are well known regulators of gene expression, but there is growing recognition that small RNAs (sRNAs) also have critically important roles in bacterial gene regulation. Many sRNAs have been identified inM. tuberculosis(Mtb), but little is known about their expression, regulatory targets or roles in Mtb biology. In this study, we found that the Mtb sRNA Mcr11, which is expressed at high levels in slowly replicating Mtb and during mouse infection, regulates expression of several target genes involved in central metabolism. Importantly, we also discovered thatmcr11has unexpected requirements for stable expression in mycobacteria. In particular, we identified RNA sequence elements immediately downstream ofmcr11that enhance transcription termination and production of mature Mcr11 RNA in TB-complex mycobacteria. Meanwhile, ectopic expression of Mcr11 was unstable in a non-pathogenic strain of mycobacteria, suggesting that factors specific to pathogenic mycobacteria are required for the stable production of Mcr11. These studies identify sRNA stability as a new frontier for understanding gene expression in Mtb.
Electrospinning of pure, native, cross-linker free self-supported collagen membrane
Authors: Dems Dounia , Rodrigues da Silva Julien , Hélary Christophe , Wien Frank , Schanne-Klein Marie-Claire , Laberty-Robert Christel , Krins Natacha , Aimé Carole
Published: April 2019

Electrospinning (ES) is an extremely promising method for the preparation of self-supported membranes for tissue engineering by mimicking the 3D fibrillar structure of the extracellular matrix. Conflicting results about collagen ES in the literature concern the conditions of collagen solubilization to improve electrospinnability, and the use of co-polymers and chemical cross-linkers to stabilize the structure of collagen membranes. Here we report for the first time (1) the ES of pure and native collagen into a self-supported membrane in absence of polymer support and (2) the preservation of the membrane integrity in hydrated media in absence of crosslinker. We use a multiscale approach to characterize collagen native structure at the molecular level using synchrotron radiation circular dichroism, and to investigate collagen hierarchical organization within the self-supported membrane using electron and multiphoton microscopies. Finally, we show that the membranes are perfectly suited for cell adhesion and spreading, making very promising candidates for the development of advanced biomaterials.