bluuebunny/crossref_metadata_2025 huggingface dataset:
Universal assay for measuring vertebrate telomeres by real-time quantitative PCR
Authors: Hudon Stephanie F , Palencia Hurtado Esteban , Beck James D. , Burden Steven J. , Bendixsen Devin P. , Callery Kathleen R. , Forbey Jennifer S. , Waits Lisette P. , Miller Robert A. , Nielsen Olafur K. , Heath Julie A. , Hayden Eric J.
Published: October 2019

Telomere length dynamics are an established biomarker of health and aging in animals. The study of telomeres in numerous species has been facilitated by methods to measure telomere length by real-time quantitative PCR (qPCR). In this method, telomere length is determined by quantifying the amount of telomeric DNA repeats in a sample and normalizing this to the total amount of genomic DNA. This normalization requires the development of genomic reference primers suitable for qPCR, which remains challenging in non-model organism with genomes that have not been sequenced. Here we report reference primers that can be used in qPCR to measure telomere lengths in any vertebrate species. We designed primer pairs to amplify genetic elements that are highly conserved between evolutionarily distant taxa and tested them in species that span the vertebrate tree of life. We report five primer pairs that meet the specificity and reproducibility standards of qPCR. In addition, we demonstrate how to choose the best primers for a given species by testing the primers on multiple individuals within a species and applying an established computational tool. These reference primers can facilitate the application of qPCR-based telomere length measurements in any vertebrate species of ecological or economic interest.
Multifaceted diversity traits of crucial microbial groups in biological soil crusts promote soil multifunctionality
Authors: Li Hua , Chen Youxin , Yu Gongliang , Rossi Federico , Huo Da , De Philippis Roberto , Cheng Xiaoli , Wang Weibo , Li Renhui
Published: October 2019

Abstracts

Microbial diversity is one of the most important drivers on ecosystem to maintain the simultaneous performance of functions (multifunctionality, MF) under climatic oscillation. However, existing studies typically consider taxonomic richness or Shannon index at the community level in which relations between diversity and functioning are not highly consistent. To disentangle the underlying linkages in real-world ecosystems, we conducted field investigation on biological soil crusts of Tibetan Plateau and evaluated multiple diversity facets (i.e., richness, evenness, and phylogeny-related trait dissimilarity) of carbon- and nitrogen-fixing functional groups (FGs). Seven crucial variables of soil functioning were also identified to calculate MF. We found that the integrated index, invoking multiple diversity components, was a stronger predictor on MF than richness. Moreover, the divergent performance of different diversity facets determined the idiosyncratic diversity effect of each FG on the MF. Namely, richness was the dominant factor for diazotrophs to maximize MF, whereas phylogenetic dissimilarity was the most important one for phototrophs. The heterogeneity among the focal FGs derived from the significant differentiation of the extent of multifunctional redundancy. Collectively, we speculated that the multifaceted diversity pattern depicts the response ability of crucial FGs by which biocrusts stabilize MF under environmental perturbation. Taken together, our results provided a perspective to bridge the gap between taxonomic and trait-based approaches for elucidating the biodiversity-ecosystem functioning relationship, and could ultimately help to boost the practices of dryland management against global change.
An experimentally-derived measure of inter-replicate variation in reference samples: the same-same permutation methodology
Authors: Handler David C. , Haynes Paul A.
Published: October 2019

The multiple testing problem is a well-known statistical stumbling block in high-throughput data analysis, where large scale repetition of statistical methods introduces unwanted noise into the results. While approaches exist to overcome the multiple testing problem, these methods focus on theoretical statistical clarification rather than incorporating experimentally-derived measures to ensure appropriately tailored analysis parameters. Here, we introduce a method for estimating inter-replicate variability in reference samples for a quantitative proteomics experiment using permutation analysis. This can function as a modulator to multiple testing corrections such as the Benjamini-Hochberg ordered Q value test. We refer to this as a ‘same-same’ analysis, since this method incorporates the use of six biological replicates of the reference sample and determines, through non-redundant triplet pairwise comparisons, the level of quantitative noise inherent within the system. The method can be used to produce an experiment-specific Q value cut-off that achieves a specified false discovery rate at the quantitation level, such as 1%. The same-same method is applicable to any experimental set that incorporates six replicates of a reference sample. To facilitate access to this approach, we have developed a same-same analysis R module that is freely available and ready to use via the internet.
The PMK-3 (p38) Mitochondrial Retrograde Response Functions in Intestinal Cells to Extend Life via the ESCRT Machinery
Authors: Radetskaya Oxana , Lane Rebecca K. , Friedman Troy , Garrett Aria , Nguyen Michael , Borror Megan B. , Russell Joshua , Rea Shane L.
Published: October 2019

The p38 mitogen-activated protein kinase (MAPK) PMK-3 controls a life-extending retrograde response in the nematodeCaenorhabditis elegansthat is activated following mitochondrial electron transport chain (ETC) disruption and is distinct from known longevity-promoting pathways. Here we show that the long isoform of PMK-3 expressed exclusively in the gut, rather than neurons, is sufficient to fully extend the life of animals exposed to mild ETC dysfunction. Surprisingly, constitutive activation of PMK-3 using a gain-of-function MAP3K/DLK-1 mutant does not extend the life of wild-type worms due to dampening of the DLK-1/PMK-3 signaling axis with age. We further show that core components of the ESCRT-III machinery, including ISTR-1, CHMP2B (CC01A4.2) and RAB-11.1, are required for life extension following ETC disruption. ESCRT proteins are needed for extracellular vesicle (EV) formation, lysosomal traffic and other functions requiring membrane encapsulation away from the cytoplasm. Together, our findings underscore PMK-3 as a pivotal factor controlling life extension in worms following mitochondrial ETC disruption and illustrate the importance of the endomembrane system to this process. Our findings raise the possibility that EVs may act as intra-organismal signaling vehicles to control aging.
Fluorescent reporter plasmids for single-cell and bulk-level composition assays inE. faecalis
Authors: Hallinen Kelsey M. , Guardiola-Flores Keanu A. , Wood Kevin B.
Published: October 2019

Fluorescent reporters are an important tool for monitoring dynamics of bacterial populations at the single cell and community level. While there are a large range of reporter constructs available–particularly for common model organisms likeE. coli–fewer options exist for other species, includingE. faecalis, a gram-positive opportunistic pathogen. To expand the potential toolkit available forE. faecalis, we modified a previously developed reporter plasmid (pBSU101) to express one of nine different fluorescent reporters and confirmed that all constructs exhibited detectable fluorescence in singleE. faecaliscells and mixed biofilm communities. To identify promising constructs for bulk-level experiments, we then measured the fluorescence spectra fromE. faecalispopulations in microwell plate (liquid) cultures during different growth phases. Cultures showed density- and reporter-specific variations in fluorescent signal, though spectral signatures of all reporters become clear in late-exponential and stationary-phase populations. Based on these results, we identified six pairs of reporters that can be combined with simple spectral unmixing to accurately estimate population composition in 2-strain mixtures at or near stationary phase. This approach offers a simple and scalable method for selection and competition experiments in simple two-species populations. Finally, we modified the construct to express codon-optimized variants of blue (BFP) and red (RFP) reporters and show that they lead to increased fluorescence in exponentially growing cells. As a whole, the results inform the scope of application of different reporters and identify both single reporters and reporter pairs that are promising for fluorescence-based assays at bulk and single-cell levels inE. faecalis.
REP-X: An Evolution-guided Strategy for the Rational Design of Cysteine-less Protein Variants
Authors: Dalton Kevin , Lopez Tom , Pande Vijay , Frydman Judith
Published: October 2019

Site-specific labeling of proteins is often a prerequisite for biophysical and biochemical characterization. Chemical modification of a unique cysteine residue is among the most facile methods for site-specific labeling of proteins. However, many proteins have multiple reactive cysteines, which must be mutated to other residues to enable labeling of unique positions. This trial-and-error process often results in cysteine-free proteins with reduced activity or stability. Herein we describe a general methodology to rationally engineer cysteine-less proteins. Briefly, natural variation across orthologues is exploited to identify suitable cysteine replacements compatible with protein activity and stability. As a proof-of-concept, we recount the successful engineering of a cysteine-less mutant of the group II chaperonin from methanogenic archaeon Methanococcus maripaludis. A webapp, REP-X (Replacement at Endogenous Positions from eXtant sequences), which enables users to design their own cysteine-less protein variants, will make this rational approach widely available.
Autonomous bioluminescence imaging of single mammalian cells with the bacterial bioluminescence system
Authors: Gregor Carola , Pape Jasmin K. , Gwosch Klaus C. , Gilat Tanja , Sahl Steffen J. , Hell Stefan W.
Published: October 2019

Bioluminescence based imaging of living cells has become an important tool in biological and medical research. However, many bioluminescence imaging applications are limited by the requirement of an externally provided luciferin substrate and the low bioluminescence signal which restricts the sensitivity and spatiotemporal resolution. The bacterial bioluminescence system is fully genetically encodable and hence produces autonomous bioluminescence without an external luciferin, but its brightness in cell types other than bacteria has so far not been sufficient for imaging single cells. We coexpressed codon-optimized forms of the bacterialluxCDABEandfrpgenes from multiple plasmids in different mammalian cell lines. Our approach produces high luminescence levels that are comparable to firefly luciferase, thus enabling autonomous bioluminescence microscopy of mammalian cells.

Significance statement

Bioluminescence is generated by luciferases that oxidize a specific luciferin. The enzymes involved in the synthesis of the luciferin from widespread cellular metabolites have so far been identified for only two bioluminescence systems, those of bacteria and fungi. In these cases, the complete reaction cascade is genetically encodable, meaning that heterologous expression of the corresponding genes can potentially produce autonomous bioluminescence in cell types other than the bacterial or fungal host cells. However, the light levels achieved in mammalian cells so far are not sufficient for single-cell applications. Here we present, for the first time, autonomous bioluminescence images of single mammalian cells by coexpression of the genes encoding the six enzymes from the bacterial bioluminescence system.
Ratiometric bioluminescent sensors towards in vivo imaging of bacterial signaling
Authors: Dippel A. B , Anderson W. A. , Park J. H. , Yildiz F. H. , Hammond M.C.
Published: October 2019

Second messenger signaling networks allow cells to sense and adapt to changing environmental conditions. In bacteria, the nearly ubiquitous second messenger molecule cyclic di-GMP coordinates diverse processes such as motility, biofilm formation, and virulence. In bacterial pathogens, these signaling networks allow the bacteria to survive changing environment conditions that are experienced during infection of a mammalian host. While studies have examined the effects of cyclic di-GMP levels on virulence in these pathogens, it has previously not been possible to visualize cyclic di-GMP levels in real time during the stages of host infection. Towards this goal, we generate the first ratiometric, chemiluminescent biosensor scaffold that selectively responds to c-di-GMP. By engineering the biosensor scaffold, a suite of Venus-YcgR-NLuc (VYN) biosensors is generated that provide extremely high sensitivity (KD < 300 pM) and large BRET signal changes (up to 109%). As a proof-of-concept that VYN biosensors can image cyclic di-GMP during host infection, we show that the VYN biosensors function in the context of a tissue phantom model, with only ∼103-104 biosensor-expressing cells required for the measurement. Furthermore, the stable BRET signal suggests that the sensors could be used for long-term imaging of cyclic di-GMP dynamics during host infection. The VYN sensors developed here can serve as robust in vitro diagnostic tools for high throughput screening, as well as genetically encodable tools for monitoring the dynamics of c-di-GMP in live cells, and lay the groundwork for live cell imaging of c-di-GMP dynamics in bacteria during host infection, and other complex environments.
Two brain pathways initiate distinct forward walking programs inDrosophila
Authors: Bidaye Salil S. , Laturney Meghan , Chang Amy K. , Liu Yuejiang , Bockemühl Till , Büschges Ansgar , Scott Kristin
Published: October 2019

An animal at rest or engaged in stationary behaviors can instantaneously initiate goal-directed walking. How descending brain inputs trigger rapid transitions from a non-walking state to an appropriate walking state is unclear. Here, we identify two specific neuronal classes in theDrosophilabrain that drive two distinct forward walking programs in a context-specific manner. The first class, named P9, consists of descending neurons that drive forward walking with ipsilateral turning. P9 receives inputs from central courtship-promoting neurons and visual projection neurons and is necessary for a male to track a female during courtship. The second class comprises novel, higher order neurons, named BPN, that drives straight, forward walking. BPN is required for high velocity walking and is active during long, fast, straight walking bouts. Thus, this study reveals separate brain pathways for object-directed steering and fast straight walking, providing insight into how the brain initiates different walking programs.
The conserved DNMT1 dependent methylation regions in human cells are vulnerable to environmental rotenone
Authors: Freeman Dana M. , Lou Dan , Li Yanqiang , Martos Suzanne N. , Wang Zhibin
Published: October 2019

Allele-specific DNA methylation (ASM) describes genomic loci that maintain CpG methylation at only one inherited allele rather than having coordinated methylation across both alleles. The most prominent of these regions are germline ASMs (gASMs) that control the expression of imprinted genes in a parent of origin-dependent manner and are associated with disease. However, our recent report reveals numerous ASMs at non-imprinted genes. These non-germline ASMs are dependent on DNA methyltransferase 1 (DNMT1) and strikingly show the feature of random, switchable monoallelic methylation patterns in the mouse genome. The significance of these ASMs to human health has not been explored. Due to their shared allelicity with gASMs, herein, we propose that non-traditional ASMs are sensitive to exposures in association with human disease. We first explore their conservancy in the human genome. Our data show that our putative non-germline ASMs were in conserved regions of the human genome and located adjacent to genes vital for neuronal development and maturation. We next tested the hypothesized vulnerability of these regions by exposing human embryonic kidney cell HEK293 with the neurotoxicant rotenone for 24h. Indeed,14 genes adjacent to our identified regions were differentially expressed from RNA-sequencing. We analyzed the base-resolution methylation patterns of the predicted non-germline ASMs at two neurological genes,HCN2andNEFM, with potential to increase the risk of neurodegeneration. Both regions were significantly hypomethylated in response to rotenone. Our data indicate that non-germline ASMs seem conserved between mouse and human genomes, overlap important regulatory factor binding motifs, and regulate the expression of genes vital to neuronal function. These results support the notion that ASMs are sensitive to environmental factors and may alter the risk of neurological disease later in life by disrupting neuronal development.
Estimating the genome-wide contribution of selection to temporal allele frequency change
Authors: Buffalo Vince , Coop Graham
Published: October 2019

Rapid phenotypic adaptation is often observed in natural populations and selection experiments. However, detecting the genome-wide impact of this selection is difficult, since adaptation often proceeds from standing variation and selection on polygenic traits, both of which may leave faint genomic signals indistinguishable from a noisy background of genetic drift. One promising signal comes from the genome-wide covariance between allele frequency changes observable from temporal genomic data, e.g. evolve-and-resequence studies. These temporal covariances reflect how heritable fitness variation in the population leads changes in allele frequencies at one timepoint to be predictive of the changes at later timepoints, as alleles are indirectly selected due to remaining associations with selected alleles. Since genetic drift does not lead to temporal covariance, we can use these covariances to estimate what fraction of the variation in allele frequency change through time is driven by linked selection. Here, we reanalyze three selection experiments to quantify the effects of linked selection over short timescales using covariance among time-points and across replicates. We estimate that at least 17% to 37% of allele frequency change is driven by selection in these experiments. Against this background of positive genome-wide temporal covariances we also identify signals of negative temporal covariance corresponding to reversals in the direction of selection for a reasonable proportion of loci over the time course of a selection experiment. Overall, we find that in the three studies we analyzed, linked selection has a large impact on short-term allele frequency dynamics that is readily distinguishable from genetic drift.

Significance Statement

A long-standing problem in evolutionary biology is to understand the processes that shape the genetic composition of populations. In a population without migration, the two processes that change allele frequencies are selection, which increases beneficial alleles and removes deleterious ones, and genetic drift which randomly changes frequencies as some parents contribute more or less alleles to the next generation. Previous efforts to disentangle these processes have used genomic samples from a single timepoint and models of how selection affects neighboring sites (linked selection). Here, we use genomic data taken through time to quantify the contributions of selection and drift to genome-wide frequency changes. We show selection acts over short timescales in three evolve-and-resequence studies and has a sizable genome-wide impact.
Multiphoton imaging of neural structure and activity in Drosophila through the intact cuticle
Authors: Aragon Max Jameson , Wang Mengran , Mok Aaron T. , Shea Jamien , Kim Haein , Barkdull Nathan , Xu Chris , Yapici Nilay
Published: October 2019

We developed a multiphoton imaging method to capture neural structure and activity in behaving flies through the intact cuticles. Our measurements show that the fly head cuticle has surprisingly high transmission at wavelengths > 900 nm, and the difficulty of through-cuticle imaging is due to the air sacs and/or fat tissue underneath the head cuticle. By compressing the air sacs, we performed deep multiphoton imaging of fly brains through the intact cuticle. Our anatomical and functional imaging results show that 2- and 3-photon imaging are comparable in superficial regions such as the mushroom body, but 3-photon imaging is superior in deeper regions such as the central complex and beyond. We further demonstrated 2-photon through-cuticle functional imaging of odor-evoked calcium responses from the mushroom body γ-lobes in behaving flies short-term and long-term (12 consecutive hours). The through-cuticle imaging method developed here extends the time limits of in vivo imaging in flies, and opens up new ways to capture neural structure and activity from the intact fly brain.
Remote control of neural function by X-ray-induced scintillation
Authors: Matsubara Takanori , Yanagida Takayuki , Kawaguchi Noriaki , Nakano Takashi , Yoshimoto Junichiro , Sezaki Maiko , Takizawa Hitoshi , Tsunoda Satoshi P. , Horigane Shin-ichiro , Ueda Shuhei , Takemoto-Kimura Sayaka , Kandori Hideki , Yamanaka Akihiro , Yamashita Takayuki
Published: October 2019

Scintillators emit visible luminescence when irradiated with X-rays. Given the unlimited tissue penetration of X-rays, the employment of scintillators could enable remote optogenetic control of neural functions at any depth of the brain. Here we show that a yellow-emitting inorganic scintillator, Ce-doped Gd3(Al,Ga)5O12 (Ce:GAGG), could effectively activate red-shifted excitatory and inhibitory opsins, ChRmine and GtACR1, respectively. Using injectable Ce:GAGG microparticles, we successfully activated and inhibited midbrain dopamine neurons in freely moving mice by X-ray irradiation, producing bidirectional modulation of place preference behavior. Ce:GAGG microparticles were non-cytotoxic and biocompatible, allowing for chronic implantation. Pulsed X-ray irradiation at a clinical dose level was sufficient to elicit behavioral changes without reducing the number of radiosensitive cells in the brain and bone marrow. Thus, scintillator-mediated optogenetics enables less invasive, wireless control of cellular functions at any tissue depth in living animals, expanding X-ray applications to functional studies of biology and medicine.
Whole brain delivery of an instability-proneMecp2transgene improves behavioral and molecular pathological defects in mouse models of Rett syndrome
Authors: Luoni Mirko , Giannelli Serena , Indrigo Marzia , Niro Antonio , Massimino Luca , Iannielli Angelo , Passeri Laura , Russo Fabio , Morabito Giuseppe , Calamita Piera , Gregori Silvia , Deverman Benjamin , Broccoli Vania
Published: October 2019

Rett syndrome (RTT) is an incurable neurodevelopmental disorder caused by mutations in the gene encoding for methyl-CpG binding-protein 2 (MeCP2). Gene therapy for this disease presents inherent hurdles sinceMECP2is expressed throughout the brain and its duplication leads to severe neurological conditions as well. However, the recent introduction of AAV-PHP.eB, an engineered capsid with an unprecedented efficiency in crossing the blood-brain barrier upon intravenous injection, has provided an invaluable vehicle for gene transfer in the mouse nervous system. Herein, we use AAV-PHP.eB to deliver an instability-proneMecp2(iMecp2) transgene cassette which, increasing RNA destabilization and inefficient protein translation of the viralMecp2transgene, limits supraphysiological Mecp2 protein levels in transduced neural tissues. Intravenous injections of the PHP.eB-iMecp2virus in symptomatic male and femaleMecp2mutant mice significantly ameliorated the disease progression with improved locomotor activity, coordination, lifespan and normalization of altered gene expression and mTOR signaling. Remarkably, PHP.eB-iMecp2administration did not result in severe toxicity effects either in femaleMecp2mutant or in wild-type animals. In contrast, we observed a strong immune response to the transgene in treated maleMecp2mutant mice that was overcome by immunosuppression. Overall, PHP.eB-mediated delivery of theiMecp2cassette provided widespread and efficient gene transfer maintaining physiological Mecp2 protein levels in the brain. This combination defines a novel viral system with significant therapeutic efficacy and increased safety which can contribute to overcome the hurdles that are delaying clinical applications of gene therapy for RTT.

One Sentence Summary

Global brain transduction of the instability-proneMecp2transgene by systemic AAV-PHP.eB administration is both safe and effective in protecting male and femaleMecp2mutant mice from the RTT disease phenotype.
Apparent Propagator Anisotropy from reduced Diffusion MRI acquisitions
Authors: Aja-Fernández Santiago , Tristán-Vega Antonio , Jones Derek
Published: October 2019

The Propagator Anisotropy (PA) is a measurement of the orientational variability inside a tissue estimated from diffusion MRI using the Ensemble Average diffusion Propagator (EAP). It is based on the quantification of the angular difference between the propagator in a specific voxel and its isotropic counterpart. The PA has shown the ability to reveal microstructural information of interest and meaningful descriptive maps inside the white matter. However, the use of PA is not generalized among the clinical community, due to the great amount of data needed for its calculation, together with the associated long processing times. In order to calculate the PA, the EAP must also be properly estimated. This task would require a dense sampling of the Cartesian q-space. Alternatively, more efficient techniques have been proposed in the last decade. Even so, all of them imply acquiring a large number of diffusion gradients with different b-values and long processing times.

In this work, we propose an alternative implementation to drastically reduce the number of samples needed, as well as boosting the estimation procedure. We avoid the calculation of the whole EAP by assuming that the diffusion anisotropy is roughly independent from the radial direction. With such an assumption, we achieve a closed-form expression for a measure similar to the PA but using information from one single shell: the Apparent Propagator Anisotropy (APA). The new measure remains compatible with standard acquisition protocols commonly used for HARDI (based on just one b-value). The intention of the APA is not to exactly replicate the PA but inferring microstructural information with comparable discrimination power as the PA but using a reduced amount of data.

We report extensive results showing that the proposed measures present a robust behavior in clinical studies and they are computationally efficient and robust when compared with PA and other anisotropy measures.
Impact of small RNAs in retrograde signalling pathways inArabidopsis thaliana
Authors: Habermann Kristin , Tiwari Bhavika , Krantz Maria , Adler Stephan O. , Klipp Edda , Arif M. Asif , Frank Wolfgang
Published: October 2019

Chloroplast perturbations activate retrograde signalling pathways causing dynamic changes of gene expression. Besides transcriptional control of gene expression different classes of small non-coding RNAs (sRNAs) act in gene expression control, but comprehensive analyses regarding their role in retrograde signalling is lacking. We performed sRNA profiling in response to norflurazon (NF) that provokes retrograde signals inA. thalianawild type and the two retrograde signalling mutantsgun1andgun5. The RNA samples were also used for mRNA and long non-coding RNA (lncRNA) profiling to link altered sRNA levels to changes of their cognate target RNAs. We identified 122 sRNAs from all known sRNA classes that were responsive to NF in wild type. Strikingly, 140 and 213 sRNAs were found to be differentially regulated in both mutants indicating a retrograde control of these sRNAs. Concomitant with the changes in sRNA expression we detected about 1500 differentially expressed mRNAs in the NF treated wild type and around 900 and 1400 mRNAs that were differentially regulated in thegun1andgun5mutant with a high proportion (~30%) of genes encoding plastid proteins. Furthermore, around 20% of predicted miRNA targets code for plastid localised proteins. The analyses of sRNA-target pairs identified pairs with an anticorrelated expression as well pairs showing other expressional relations pointing to a role of sRNAs in balancing transcriptional changes upon retrograde signals. Based on the comprehensive changes in sRNA expression we assume a considerable impact of sRNAs in retrograde-dependent transcriptional changes to adjust plastidic and nuclear gene expression.

Significance statement

Perturbations of plastid functions trigger retrograde signalling to adjust plastidic and nuclear gene expression, however, the role of small non-coding RNAs acting as regulators in these pathways is not well understood. We analysed small non-coding RNA expression in response to retrograde signals inA. thalianawild type and two retrograde signalling mutants and identified members of all known small non-coding RNA classes pointing to a functional role of these RNA classes in retrograde pathways.
Substrate-mediated regulation of the arginine transporter ofToxoplasma gondii
Authors: Rajendran Esther , Clark Morgan , Goulart Cibelly , Steinhöfel Birte , Tjhin Erick T. , Smith Nicholas C. , Kirk Kiaran , van Dooren Giel G.
Published: October 2019

Intracellular parasites, such as the apicomplexanToxoplasma gondii, are adept at scavenging nutrients from their host. However, there is little understanding of how parasites sense and respond to the changing nutrient environments they encounter during an infection.TgApiAT1, a member of the apicomplexan ApiAT family of amino acid transporters, is the major uptake route for the essential amino acid L-arginine (Arg) inT. gondii. Here, we show that the abundance ofTgApiAT1, and hence the rate of uptake of Arg, is regulated by the availability of Arg in the parasite’s external environment, increasing in response to decreased [Arg]. Using a luciferase-based ‘biosensor’ strain ofT. gondii, we demonstrate that parasites vary the expression ofTgApiAT1 in different organs within their host, indicating that parasites are able to modulateTgApiAT1-dependent uptake of Arg as they encounter different nutrient environmentsin vivo. Finally, we show that Arg-dependent regulation ofTgApiAT1 expression is post-transcriptional, mediated by an upstream open reading frame (uORF) in theTgApiAT1 transcript, and we provide evidence that the peptide encoded by this uORF is critical for mediating regulation. Together, our data reveal the mechanism by which an apicomplexan parasite responds to changes in the availability of a key nutrient.
Trade-offs between host tolerances to different pathogens in plant-virus interactions
Authors: Montes Nuria , Vijayan Viji , Pagán Israel
Published: October 2019

Although accumulating evidence indicates that tolerance is a plant defence strategy against pathogens as widespread as resistance, how plants evolve tolerance is poorly understood. Theory predicts that hosts will evolve to maximize tolerance or resistance, but not both. Remarkably, most experimental works failed in finding this trade-off. We tested the hypothesis that the evolution of tolerance to one virus is traded-off against tolerance to others, rather than against resistance, and identified the associated mechanisms. To do so, we challenged eighteen Arabidopsis thaliana genotypes with Turnip mosaic virus (TuMV) and Cucumber mosaic virus (CMV). We characterized plant life-history trait modifications associated with reduced effects of TuMV and CMV on plant seed production (fecundity tolerance) and life period (mortality tolerance), both measured as a norm of reaction across viral loads (range tolerance). Also, we analysed resistance-tolerance and tolerance-tolerance trade-offs. Results indicate that tolerance to TuMV is associated with changes in the length of the pre-reproductive and reproductive periods, and tolerance to CMV with resource reallocation from growth to reproduction; and that tolerance to TuMV is traded-off against tolerance to CMV in a virulence-dependent manner. Thus, this work provides novel insights on the mechanisms of plant tolerance and highlights the importance of considering the combined effect of different pathogens to understand how plant defences evolve.
StoatyDive: Evaluation and Classification of Peak Profiles for Sequencing Data
Authors: Heyl Florian , Backofen Rolf
Published: October 2019

The prediction of binding sites (peak calling) is a common task in the data analysis of methods such as crosslinking or chromatin immunoprecipitation in combination with high-throughput sequencing (CLIP-Seq, ChIP-Seq). The predicted binding sites are often further analyzed to predict sequence motifs or structure patterns as an example. However, the obtained peak set can vary in their profile shapes because of the used peakcaller method, different binding domains of the protein, protocol biases, or other factors. Thus, a tool is missing that evaluates and classifies the predicted peaks based on their shapes. We hereby present StoatyDive, a tool that can be used to filter for specific peak profile shapes of sequencing data such as CLIP and ChIP. StoatyDive therefore fine tunes downstream analysis steps such as structure or sequence motif predictions and acts as a quality control.

With StoatyDive we were able to classify distinct peak profile shapes from CLIP-seq data of the histone stem-loop-binding protein (SLBP). We show the potential of StoatyDive, as a quality control tool and as a filter to pick different shapes based on biological or methodical questions.

StoatyDive is open source and freely available under GLP-3 athttps://github.com/BackofenLab/StoatyDiveand at biocondahttps://anaconda.org/bioconda/stoatydive.
Imprecise neural computations as source of human adaptive behavior in volatile environments
Authors: Findling Charles , Chopin Nicolas , Koechlin Etienne
Published: October 2019

Everyday life features uncertain and ever-changing situations. In such environments, optimal adaptive behavior requires higher-order inferential capabilities to grasp the volatility of external contingencies. These capabilities however involve complex and rapidly intractable computations, so that we poorly understand how humans develop efficient adaptive behaviors in such environments. Here we demonstrate this counterintuitive result: simple, low-level inferential processes involving imprecise computations conforming to the psychophysical Weber Law actually lead to near-optimal adaptive behavior, regardless of the environment volatility. Using volatile experimental settings, we further show that such imprecise, low-level inferential processes accounted for observed human adaptive performances, unlike optimal adaptive models involving higher-order inferential capabilities, their biologically more plausible, algorithmic approximations and non-inferential adaptive models like reinforcement learning. Thus, minimal inferential capabilities may have evolved along with imprecise neural computations as contributing to near-optimal adaptive behavior in real-life environments, while leading humans to make suboptimal choices in canonical decision-making tasks.
An assessment of digital literacy skills and knowledge-based competencies among librarians working in university libraries in Africa
Authors: Baro Ebikabowei Emmanuel , Obaro Onyedikachi G. , Aduba Emetarom Doris
Published: October 2019

Purpose

The purpose of this paper is to assess digital literacy skills possessed by library and information professionals working in university libraries in Africa.

Design/methodology/approach

Online questionnaire was developed to collect data from 214 librarians working in various university libraries in English-speaking countries in Africa.

Findings

The study found that librarians working in university libraries in Africa rated their database search skills, uploading documents to online platforms, skills in using different social media, sending and receiving e-mails skill, digital library development skills, skills in applying new technologies into library services, ability to create different file formats and ability to use open source software as very high. While, metadata development skills, and library website development skills were rated to be moderate and low. Overall, the librarians rated their level of digital literacy skills possessed to be moderate, and differences emerged between librarians in Nigeria and South Africa with regard to digital literacy skills possessed.

Practical implications

This study attempts to identify skills that are central to librarians working in university libraries. The study will be useful for trainers who want to arrange training for academic librarians in Africa and other developing countries. For some library schools, it may help them to review their curriculum in accordance with the required skills and competencies for academic librarians in the market.

Originality/value

Findings will be helpful to explore the skills and competencies needed by information professionals and to act as a guideline for competency development and curriculum update in library schools in developing countries.
Physical and cognitive demands of work in building construction
Authors: Rodriguez Franciscsa S. , Spilski Jan , Hekele Felix , Beese Nils Ove , Lachmann Thomas
Published: October 2019

Purpose

Investigating demands within an occupational context has always been an essential endeavor to guarantee worker well-being and performance efficiency. In blue-collar occupations, the physical demands of manual labor have always been the major focus, but recent technological changes may come with higher demands on the intellectual capacities of workers. For this reason, the purpose of this paper is to assess physical and cognitive demands that construction workers face.

Design/methodology/approach

The authors conducted a quantitative study using standardized research instruments. Construction workers of three German construction companies were asked to volunteer to participate in interviews (n=35) and a survey (n=30) that assessed the extent of physical demands and a variety of cognitive demands experienced by construction workers.

Findings

The results suggest that construction work is demanding in physical terms as well as in perceptual, psychomotor, social and cognitive terms. Using and updating specialized knowledge, giving advice and providing consultation, friendliness, assertiveness and reliability are important demands among construction workers.

Research limitations/implications

Construction workers face an undervalued level of demands in their everyday work environment. As high demands can affect well-being and mental health, construction companies would greatly benefit from investing efforts into evaluating the multi-component demands profile of their workers and the impact on their health, in particular through the strongly increasing cognitive demands due to the ongoing digitization of the sector.

Originality/value

The study identified essential demands in construction work that are relevant for the workers’ productivity and well-being.
Do academia-industry R&D collaborations necessarily facilitate industrial innovation in China?
Authors: Hou Bojun , Hong Jin , Chen Qiong , Shi Xing , Zhou Yu
Published: October 2019

Purpose

It is widely accepted that enterprises obtaining academic discoveries through R&D collaboration improve their innovation performance. However, it is not necessarily true in emerging economies, such as China and post-socialist countries in Europe. The purpose of this paper is to fill the gap by investigating how R&D collaboration between industry and academia (i.e. universities and research institutes) affects the industrial innovation performance; and whether and how intermediaries moderate their relationships.

Design/methodology/approach

This paper constructs the research model according to the knowledge production function, and the pooled ordinary least square regression is used to verify our hypotheses.

Findings

Evidence from a sample of Chinese industrial enterprises in thirty provinces spanning from 2009 to 2014 suggests that R&D collaboration with research institutes (CWR) is positively related to innovation output, while R&D collaboration with universities (CWU) exerts negative effect on innovation output measured by sales revenue of new product (NPSR). The significant moderating role of technology transfer institutions is confirmed in the negative relationship between CWU and NPSR.

Originality/value

This paper empirically examines the moderating role of intermediary organisations in academia–industry cooperation and industrial innovation, and has practical implications for the government to formulate policies to improve the quality and effectiveness of cooperation between academic and industrial sectors. These results vary in inland and coastal areas, which suggest the policy makers to formulate policies according to local conditions not only in China but also in other countries, like European countries.
Making secret sharing based cloud storage usable
Authors: Framner Erik , Fischer-Hübner Simone , Lorünser Thomas , Alaqra Ala Sarah , Pettersson John Sören
Published: October 2019

Purpose

The purpose of this paper is to develop a usable configuration management for Archistar, which utilizes secret sharing for redundantly storing data over multiple independent storage clouds in a secure and privacy-friendly manner. Selecting the optimal secret sharing parameters, cloud storage servers and other settings for securely storing the secret data shares, while meeting all of end user’s requirements and other restrictions, is a complex task. In particular, complex trade-offs between different protection goals and legal privacy requirements need to be made.

Design/methodology/approach

A human-centered design approach with structured interviews and cognitive walkthroughs of user interface mockups with system administrators and other technically skilled users was used.

Findings

Even technically skilled users have difficulties to adequately select secret sharing parameters and other configuration settings for adequately securing the data to be outsourced.

Practical implications

Through these automatic settings, not only system administrators but also non-technical users will be able to easily derive suitable configurations.

Originality/value

The authors present novel human computer interaction (HCI) guidelines for a usable configuration management, which propose to automatically set configuration parameters and to solve trade-offs based on the type of data to be stored in the cloud. Through these automatic settings, not only system administrators but also non-technical users will be able to easily derive suitable configurations.
Lawyers and the “new extraction” in Africa
Authors: Dezalay Sara
Published: October 2019

Purpose

The purpose of this paper is to examine the ongoing “new extraction” on the African continent. Contrary to mainstream scholarship and policies that see in law an external variable to remedy the “resource curse,” this paper channels attention toward the role of law as an institution of extraction in the longue durée. Unpacking the close association of law with the conversion of economic surpluses and power into enduring social relationships can help trace the mechanisms by which the uneven and unequal connection between Africa and the world is being negotiated, justified and challenged over time.

Design/methodology/approach

To this end, this paper deploys an approach anchored in political sociology of law and focuses on the roles played specifically by lawyers to trace the “interconnectedness” between European colonialism on the continent and the consolidation of the contemporary international economic and legal political order. It illustrates this approach with the case study of the “Africa” Bar in Paris as a key site in which extractive deals between multinational corporations and Francophone African states are negotiated.

Findings

This micro focus helps to explain the dual position of the “Africa” Bar in Paris, as offshore yet connected as it is shaped by both imperial legacies and ongoing waves of globalization into the African continent.

Originality/value

This approach traces a more nuanced explanation of Africa’s unequal and uneven relationship with the global economy as one shaped by the path of imperial legacies and successive and interconnected waves of globalization across Africa.
Development prioritization through analytical hierarchy process (AHP) - decision making for port selection on the one belt one road
Authors: Bhatti Omar Khalid , Hanjra Ali Raza
Published: October 2019

Purpose

This paper aims to attempt to investigate if the now-existing upstream Sost Dry Port in Gilgit-Baltistan and the prospective midstream Havelian Dry Port in Khyber Pakhtunkhwa, both part of One Belt One Road (OBOR), are expected to compete against or complement each other in terms of port efficiency and location, and which of the two ports should first be developed in the wake of uninterrupted logistics flow of cargo on the Economic Corridor.

Design/methodology/approach

Analytic hierarchy process (AHP) has been used for multi-criteria decision making by the stakeholders. Five main criteria for transhipment port selection, ranging from port location, port efficiency, intermodal connectivity, port costs and cargo volume were used with three sub-criteria each.

Findings

This study demonstrates the results that favour physical infrastructural development initiatives prioritized for the Sost Dry Port in view of its strategic location as the upstream supply chain node on the Economic Corridor, imparting efficiency to the logistics flow.

Practical implications

Results of this study may assist policymakers in achieving goals like enhancing trade facilitation, reducing congestion and increasing cargo security on OBOR.

Originality/value

To the best of the authors’ knowledge, this is the first study of its kind that analyzes priority for immediate development intervention for either Sost or Havelian Dry Port, both located on CPEC – OBOR supply chain.
Work group support as an undervalued resource of small family businesses
Authors: Royer Susanne , Bradley Lisa
Published: October 2019

Purpose

The purpose of this paper is to propose advances for developing our understandings of valuable resources in small family firms. The focus is on group support behavior within firms. It is proposed that this behavior is unique and valuable within small family firms. Propositions are presented that are built upon previous work in psychology and family business research and is linked to the concept of familiness.

Design/methodology/approach

Two small family businesses are the two cases used to investigate the propositions. Semi-structured interviews were conducted with the owner/manager and several other staff within each firm.

Findings

The paper presents evidence for the propositions, showing that work group support is unique in family firms as it is based on factors beyond the workplace. These relationships have the potential to be strong, contributing positively to the firm’s competitive advantage.

Research limitations/implications

Two in-depth case studies of firms are included in this investigation. They are in a similar industry and location. As the findings are similar it lends weight to the evidence for the propositions; however, care should be taken with generalizing to other firms in other industries.

Originality/value

This research pulls together previous evidence and understandings and applies them to a specific aspect of small family firms that has not previously been examined in depth. The increased understanding can help family firms leverage their unique competitive advantage.