bluuebunny/crossref_metadata_2025 huggingface dataset:
BLM-dependent Break-Induced Replication handles DSBs in transcribed chromatin upon impaired RNA:DNA hybrids dissolution
Authors: Cohen S , Guenolé A , Marnef A , Clouaire T , Puget N , Rocher V , Arnould C , Aguirrebengoa M , Genais M , Vernekar D , Mourad R , Borde V , Legube G
Published: May 2020

Transcriptionally active loci are particularly prone to breakage and mounting evidence suggest that DNA Double-Strand Breaks arising in genes are handled by a dedicated repair pathway, Transcription-Coupled DSB Repair (TC-DSBR), that entails R-loops accumulation and dissolution. Here, we uncovered a critical function of the Bloom RecQ DNA helicase (BLM) in TC-DSBR in human cells. BLM is recruited in a transcription dependent-manner at DSBs where it fosters resection, RAD51 binding and accurate Homologous Recombination repair. However, in a R-loop dissolution-deficient background BLM switches from promoting Homologous Recombination to promoting Break-Induced Replication (BIR), which strongly impairs cell viability. Altogether our work unveils a role for BLM in BIR at DSBs in active chromatin, and highlights the toxic potential of RNA:DNA hybrids that accumulate at these transcription-associated DSBs.
Purification of recombinant α-Synuclein: a comparison of commonly used protocols
Authors: Stephens Amberley D. , Matak-Vinkovic Dijana , Schierle Gabriele S. Kaminski
Published: May 2020

The insoluble aggregated form of the protein alpha-synuclein (aSyn) is associated with synucleinopathies, such as Parkinson’s Disease, therefore great effort is put into understanding why and how this initially soluble protein misfolds. The initial state of aSyn, e.g. presence of contaminants, adducts, oligomers or degradation products, can greatly influence the outcome of an assay, such as determining its aggregation kinetics. Here, we compare four commonly used protocols for the isolation of recombinant aSyn fromE. coliby boiling, acid precipitation, ammonium sulphate precipitation and periplasmic lysis followed by ion exchange chromatography and gel filtration. We identified, using non-denaturing electrospray ionisation mass spectrometry of the differently extracted aSyn samples, that aSyn isolated by acid precipitation and periplasmic lysis yielded the highest percentage of monomer, 100% and 96.5% respectively. aSyn purity was again highest in samples isolated by acid precipitation and periplasmic lysis, yet aggregation assays displayed differences in the aggregation rate of aSyn isolated by all four methods.

Highlights

A rapid protocol; expression day one, two step purification day two.

The periplasmic lysis-based protocol yielded 95% pure aSyn.

Acid precipitation and periplasmic lysis-based protocols yielded the highest proportion of monomeric aSyn at 100% and 96.5%, respectively.
A kinetic model of the central carbon metabolism for acrylic acid production inEscherichia coli
Authors: Oliveira Alexandre , Rodrigues Joana , Ferreira Eugénio , Rodrigues Lígia , Dias Oscar
Published: May 2020

Acrylic acid is a value-added chemical used in industry to produce diapers, coatings, paints, and adhesives, among many others. Due to its economic importance, there is currently a need for new and sustainable ways to synthesise it. Recently, the focus has been laid in the use ofEscherichia colito express the full bio-based pathway using 3-hydroxypropionate as an intermediary through three distinct pathways (glycerol, malonyl-CoA, andβ-alanine). Hence, the goals of this work were to use COPASI software to assess which of the three pathways has a higher potential for industrial-scale production, from either glucose or glycerol, and identify potential targets to improve the biosynthetic pathways yields.

When compared to the available literature, the models developed during this work successfully predict the production of 3-hydroxypropionate, using glycerol as carbon source in the glycerol pathway, and using glucose as a carbon source in the malonyl-CoA andβ-alanine pathways. Finally, this work allowed to identify four potential over-expression targets (glycerol-3-phosphate dehydrogenase (G3pD), acetyl-CoA carboxylase (AccC), aspartate aminotransferase (AspAT), and aspartate carboxylase (AspC)) that should, theoretically, result in higher AA yields.

Author summary

Acrylic acid is an economically important chemical compound due to its high market value. Nevertheless, the majority of acrylic acid consumed worldwide its produced from petroleum derivatives by a purely chemical process, which is not only expensive, but it also contributes towards environment deterioration. Hence, justifying the current need for sustainable novel production methods that allow higher profit margins. Ideally, to minimise production cust, the pathway should consist in the direct bio-based production from microbial feedstocks, such as Escherichia coli, but the current yields achieved are still to low to compete with conventional method. In this work, even though the glycerol pathway presented higher yields, we identified the malonyl-CoA route, when using glucose as carbon source, as having the most potential for industrial-scale production, since it is cheaper to implement. Furthermore, we also identified potential optimisation targets for all the tested pathways, that can help the bio-based method to compete with the conventional process.
Analyzing the neutral and adaptive background of butterfly voltinism reveals structural variation in a core circadian gene
Authors: Lindestad Olle , Nylin Sören , Wheat Christopher W. , Gotthard Karl
Published: May 2020

Many insects exhibit geographic variation in voltinism, the number of generations produced per year. This includes high-latitude species in previously glaciated areas, implying divergent selection on life cycle traits during or shortly after recent colonization. Here, we use a whole-genome approach to genetically characterize a set of populations of the butterflyPararge aegeriathat differ in voltinism. We construct a high-quality de novo genome forP. aegeria, and assess genome-wide genetic diversity and differentiation between populations. We then use the inferred phylogeographic relationships as the basis for a scan for loci showing signs of divergent selection associated with voltinism differences. The genic outliers detected include population-specific mutations of circadian loci, most notably a locally fixed 97-amino acid deletion in the circadian gene timeless. Variation in timeless has previously been implicated as underlying variation in life cycle regulation in wild populations in our study species, as well as in other insects. These results add to a growing body of research framing circadian gene variation as a mechanism for generating local adaptation of life cycles.
Upscaling ofIn VivoHR-pQCT Images Enables Accurate Simulations of Human Microstructural Bone Adaptation
Authors: Ohs Nicholas , Tourolle né Betts Duncan C. , Atkins Penny R. , Sebastian Stephanie , van Rietbergen Bert , Blauth Michael , Christen Patrik , Müller Ralph
Published: May 2020

In silicotrials of treatments in a virtual physiological human (VPH) would revolutionize research in the biomedical field. Hallmarks of bone disease and treatments can already be simulated in pre-clinical models and inex vivodata of humans using microstructural bone adaptation simulations. The increasing availability ofin vivohigh resolution peripheral quantitative computed tomography (HR-pQCT) images provides novel opportunities to validate and ultimately utilize microstructural bone adaptation simulations to improve our understanding of bone diseases and move towardsin silicoVPH decision support systems for clinicians.

In the present study, we investigated if microstructural bone adaptation simulations ofin vivohuman HR-pQCT images yielded accurate results. Since high-resolution ground truth images cannot be obtainedin vivo, we applied anex vivoapproach to study resolution dependence and the effect of upscaling on morphometric accuracy. To address simulation initialisation issues, we developed an input regularisation approach to reduce initialisation shocks observed in microstructural bone adaptation simulations and evaluated upscaling as a way to improve the accuracy of model inputs. Finally, we compared ourex vivoresults to simulations run onin vivoimages to investigate whetherin vivoimage artefacts further affect simulation outcomes.
An autoregulatory switch in sex-specificphf7transcription causes loss of sexual identity and tumors in theDrosophilafemale germline
Authors: Smolko Anne E. , Shapiro-Kulnane Laura , Salz Helen K.
Published: May 2020

Maintenance of germ cell sexual identity is essential for reproduction. Entry into the spermatogenesis or oogenesis pathway requires that the appropriate gene network is activated and the antagonist network is silenced. For example, inDrosophilafemale germ cells, forced expression of the testis-specific PHD finger protein 7 (PHF7) disrupts oogenesis leading to either an agametic or germ cell tumor phenotype. Here we show that PHF7 expressing ovarian germ cells inappropriately express hundreds of genes, many of which are male germline genes. We find that the majority of genes under PHF7 control in female germ cells are not under PHF7 control in male germ cells, suggesting that PHF7 is acting in a tissue-specific manner. Remarkably, transcriptional reprogramming includes a positive autoregulatory feedback mechanism in which ectopic PHF7 overcomes its own transcriptional repression through promoter switching. Furthermore, we find that tumorigenic capacity is dependent on the dosage ofphf7. This study reveals that high levels of ectopic PHF7 in female germ cells leads to a loss of sexual identity and promotion of a regulatory circuit beneficial for tumor initiation and progression.
ToxoplasmaTgATG9 is critical for autophagy and long-term persistence in tissue cysts
Authors: Smith David , Kannan Geetha , Coppens Isabelle , Wang Fengrong , Nguyen Hoa Mai , Cerutti Aude , Schultz Tracey L. , Rimple Patrick A. , Di Cristina Manlio , Besteiro Sébastien , Carruthers Vern B.
Published: May 2020

Many of the world’s warm-blooded species are chronically infected withToxoplasma gondiitissue cysts, including up to an estimated one third of the global human population. The cellular processes that permit long-term parasite persistence within the cyst are largely unknown, not only forT. gondiibut also for related coccidian parasites that impact human and animal health. A previous study revealed an accumulation of autophagic material in the lysosome-like Vacuolar Compartment (VAC) of chronic stage bradyzoites lacking functional cathepsin L protease (TgCPL) activity. Furthermore, it was shown that TgCPL knockout bradyzoites have compromised viability, indicating the turnover of autophagic material could be necessary for bradyzoite survival. However, the extent to which autophagy itself contributes to bradyzoite development and fitness remained unknown. Herein we show that genetic ablation ofTgATG9substantially reduces canonical autophagy and compromises bradyzoite viability. Transmission electron microscopy revealed structural abnormalities occurring in Δatg9bradyzoites, including disorganization of the inner membrane complex and plasma membrane, the occurrence of multiple nuclei within a single bradyzoite cell, as well as various anomalies associated with the VAC. TgATG9-deficient bradyzoites accumulated significantly less undigested material in the VAC upon inhibition of TgCPL activity, suggesting that autophagy contributes material to the VAC for degradation. Intriguingly, abnormal mitochondria networks were observed in TgATG9-deficient bradyzoites. They were thin and elongated and often adopted a horseshoe conformation. Some abnormal mitochondrial structures were found to contain numerous different cytoplasmic components and organelles. Bradyzoite fitness was found to be drastically compromised, bothin vitroand in mice, with very few brain cysts identified in mice 5 weeks post-infection. Taken together, our data suggests that TgATG9, and by extension autophagy, is critical for cellular homeostasis in bradyzoites and is necessary for long-term persistence within the cyst of this coccidian parasite.
Compact and contactless reflectance confocal microscope for neurosurgery
Authors: Cui Jiahe , Turcotte Raphaël , Hampson Karen M. , Wincott Matthew , Schmidt Carla C. , Emptage Nigel J. , Charalampaki Patra , Booth Martin J.
Published: May 2020

Visual guidance at the cellular level during neurosurgical procedures is essential for complete tumour resection. We present a compact reflectance confocal microscope with a 20 mm working distance that provided <1.2 µm spatial resolution over a 600 µm × 600 µm field of view in the near-infrared region. A physical footprint of 200 mm × 550 mm was achieved using only standard off-the-shelf components. Theoretical performance of the optical design was first evaluated via commercial Zemax software. Then three specimens from rodents: fixed brain, frozen calvaria and live hippocampal slices, were used to experimentally assess system capability and robustness. Results show great potential for the proposed system to be translated into use as a next generation label-free and contactless neurosurgical microscope.
Establishing a transcriptome-based drug discovery paradigm for neurodevelopmental disorders
Authors: Dhindsa Ryan S. , Zoghbi Anthony W. , Krizay Daniel K. , Vasavda Chirag , Goldstein David B.
Published: May 2020

Advances in genetic discoveries have created substantial opportunities for precision medicine in neurodevelopmental disorders. Many of the genes implicated in these diseases encode proteins that regulate gene expression, such as chromatin associated proteins, transcription factors, and RNA-binding proteins. The identification of targeted therapeutics for individuals carrying mutations in these genes remains a challenge, as the encoded proteins can theoretically regulate thousands of downstream targets in a considerable number of cell types. Here, we propose the application of a drug discovery approach called “transcriptome reversal” for these disorders. This approach, originally developed for cancer, attempts to identify compounds that reverse gene-expression signatures associated with disease states.
Depth relationships and measures of tissue thickness in dorsal midbrain
Authors: Truong Paulina , Kim Jung Hwan , Savjani Ricky , Sitek Kevin R. , Hagberg Gisela E. , Scheffler Klaus , Ress David
Published: May 2020

Dorsal human midbrain contains two nuclei with clear laminar organization, the superior and inferior colliculi. These nuclei extend in depth between the superficial dorsal surface of midbrain and a deep midbrain nucleus, the periaqueductal gray matter (PAG). The PAG, in turn, surrounds the cerebral aqueduct (CA). This study examined the use of two depth metrics to characterize depth and thickness relationships within dorsal midbrain using the superficial surface of midbrain and CA as references. The first utilized nearest-neighbor Euclidean distance from one reference surface, while the second used a level-set approach that combines signed distance from both reference surfaces. Both depth methods provided similar functional depth profiles generated by saccadic eye movements in a functional MRI task, confirming their efficacy for superficial functional activity. Next, the boundaries of the PAG were estimated using Euclidean distance together with elliptical fitting, indicating that the PAG can be readily characterized by a smooth surface surrounding PAG. Finally, we used the level-set approach to measure tissue depth between the superficial surface and the PAG, thus characterizing the variable thickness of the colliculi. Overall, this study demonstrates depth-mapping schemes for human midbrain that enables accurate segmentation of the PAG and consistent depth and thickness estimates of the superior and inferior colliculi.
A druggable oxidative folding pathway in the endoplasmic reticulum of human malaria parasites
Authors: Cobb David W. , Kudyba Heather M. , Villegas Alejandra , Hoopmann Michael R. , Baptista Rodrigo , Bruton Baylee , Krakowiak Michelle , Moritz Robert L. , Muralidharan Vasant
Published: May 2020

Malaria remains a major global health problem, and there exists a constant need to identify druggable weaknesses inP. falciparumbiology. The endoplasmic reticulum (ER) has many essential roles in the asexual lifecycle and may offer new drug targets, but it remains critically understudied. We generated conditional mutants of the putative redox-active, ER chaperonePfJ2, and show that it is essential for parasite survival. Using a redox-active cysteine crosslinker, we identify its substrates to be other mediators of oxidative folding,PfPDI8 andPfPDI11, suggesting a redox-regulatory role forPfJ2. Knockdown of these protein disulfide isomerases inPfJ2 conditional mutants show thatPfPDI11 is not essential, whilePfPDI8 is essential for asexual growth and may work in a complex with PfJ2 and other ER chaperones. Finally, we show that these redox interactions in the parasite ER are sensitive to small molecule inhibition. Together these data build a model for how oxidative folding occurs in theP. falciparumER and demonstrate its suitability for antimalarial drug development.
High-Resolution Linkage Map and QTL Analyses for Machine Harvest Traits in Autotetraploid Blueberry
Authors: Cappai Francesco , Amadeu Rodrigo R. , Benevenuto Juliana , Cullen Ryan , Garcia Alexandria , Grossman Adina , Ferrão Luís Felipe V. , Munoz Patricio
Published: May 2020

Blueberry (Vaccinium corymbosumand hybrids) is an autotetraploid crop whose commercial relevance has been growing steadily during the last twenty years. However, the ever-increasing cost of labor for hand-picking blueberry is one main constraint in competitive marketing of the fruit. Machine harvestability is, therefore, a key trait for the blueberry industry. Understanding the genetic architecture of traits through quantitative trait locus (QTL) mapping is the first step towards implementation of molecular breeding for faster genetic gains. Despite recent advances in software development for autotetraploid genetic mapping, a high-resolution map is still not available for blueberry. In this study, we crafted a map for autotetraploid low-chill highbush blueberry containing 11,292 SNP markers and a total size of 1,953.97 cM (average density of 5.78 markers/cM). This map was subsequently used to perform QTL analyses for traits relevant to machine harvesting: firmness, firmness retention, and fruit detachment force. Significant QTL peaks were identified for all the traits. The QTL intervals were further explored for putative candidate genes. Genes related to cell wall remodeling were highlighted in the firmness and firmness retention intervals. For fruit detachment force, transcription factors involved in fruit abscission were detected. Altogether, our findings provide the basis for future fine-mapping and molecular breeding efforts for machine harvesting in blueberry.
Phages - bacteria interactions network of the healthy human gut
Authors: Marbouty Martial , Thierry Agnès , Koszul Romain
Published: May 2020

With an estimated 1031particles on earth, bacteriophages are the most abundant genomic entities across all habitats and important drivers of microbial communities. Growing evidence suggest that they play roles in intestinal human microbiota homeostasis, and recent metagenomics studies on the viral fraction of this ecosystem have provided crucial information about their diversity and specificity. However, the bacterial hosts of this viral fraction, a necessary information to characterize further the balance of these ecosystems, remain poorly characterized. Here we unveil, using an enhanced metagenomic Hi-C approach, a large network of 6,651 host-phage relationships in the healthy human gut allowing to studyin situphage-host ratio. We notably found that half of these contigs appear to be sleeping prophages whereas ¼ exhibit a higher coverage than their associated MAG representing potentially active phages impacting the ecosystem. We also detect different candidate members of the crAss-like phage family as well as their bacterial hosts showing that these elusive phages infect different genus of Bacteroidetes. This work opens the door to single sample analysis and concomitant study of phages and bacteria in complex communities.
Distinct large-scale networks are associated with motor and nonmotor symptoms in Parkinson’s disease
Authors: Tinaz Sule , Kamel Serageldin , Aravala Sai S. , Sezgin Mine , Elfil Mohamed , Sinha Rajita
Published: May 2020

Parkinson’s disease (PD) is characterized clinically by various motor and nonmotor symptoms. The underlying neuroanatomical correlates of nonmotor symptoms in PD remain poorly understood. We investigated the differences and commonalities in the neuroanatomical correlates 1) between highly prevalent nonmotor features including fatigue, anxiety, depression, and apathy, and 2) between these nonmotor features and motor severity in nondemented subjects with mild PD (Hoehn & Yahr disease stage 2) using structural and functional magnetic resonance imaging. Compared to matched controls, the PD group showed atrophy in the basal ganglia and superior frontal cortex. Motor severity correlated with cortical thinning in frontotemporal regions, as well as with reduced functional connectivity between the frontostriatal and cerebellar networks. The composite nonmotor symptom severity did not show any correlation with the structural brain data, but correlated with reduced functional connectivity in a large-scale network consisting of frontostriatal, parietotemporal, and cerebellar nodes. The individual components of the nonmotor symptoms also mapped onto specific neural networks. Our study shows that motor and nonmotor features in PD are associated with distinct large-scale networks. The basal ganglia and cerebellum are core regions in all of these networks. The abnormal functional connectivity in the nonmotor network seems to be related to cognitive and emotional dysregulation and may have implications for future cognitive decline in PD.
The alveolar gas equation: do lessons from WW2 research into high flying pilots provide insights into the adaptation to high altitude flight in birds?
Authors: Seear Michael
Published: May 2020

Dalton’s law of partial pressures applies equally to birds and mammals so, as gas moves from the nostrils to the smallest gas-diffusion airways, the sequential addition of water vapour and CO2, steadily reduce the partial pressure of O2 (PO2) within the gas mixture. The PO2, at the point of gas exchange, at sea level, will be about 60 mm Hg less than the original PO2 within atmospheric air. As a result, the inspired PO2 is an inaccurate starting point for any model of oxygen transport. In humans, the interactions of gases at the point of diffusion, is described and quantified by the Alveolar Gas Equation (AGE). Its development during WW2, provided valuable insights into human gas exchange and also into the responses to high altitude flight in pilots but, except for an early study of hypoxia in pigeons, the AGE is not mentioned in the avian literature. Even detailed models of oxygen transport in birds omit the effect of CO2 clearance on pulmonary oxygen transfer. This paper develops two related arguments concerning the application of the AGE to birds. The first is that avian blood gas predictions, based on the theory of multicapillary serial arterialization (MSA), are inaccurate because they do not account for the added partial pressure of diffused CO2. The second is that the primary adaptation to hypobaric hypoxia is the same for both classes and consists of defending PaO2 by reducing PaCO2 through increasing hyperventilation. Support for the first is demonstrated by comparing PaO2 predictions made using the AGE, with published values from avian studies and also against values predicted by the theory of MSA. The second is illustrated by comparing the results of high altitude studies of both birds and humans. The application of the AGE to avian respiratory physiology would improve the predictive accuracy of models of the O2 cascade and would also provide better insights into the primary adaptation to high altitude flight.
Psi promotesDrosophilawing growth through transcriptional repression of key developmental networks
Authors: Zaytseva Olga , Mitchell Naomi C. , Delandre Caroline , Nie Zuqin , Evers Maurits , Werner Janis K. , Lis John T. , Hannan Ross D. , Levens David L. , Marshall Owen J. , Quinn Leonie M.
Published: May 2020

Psi, the sole FUSE Binding Protein (FUBP) family single stranded DNA/RNA binding protein inDrosophila, is essential for proper cell and tissue growth, however its mechanism of function remains unclear. Here we use Targeted DamID combined with RNA-sequencing to generate the first genome-wide binding and expression profiles for Psi. Surprisingly, we demonstrate Psi drives growth in theDrosophilawing through transcriptional repression of key developmental pathways (e.g. Wnt, Notch and TGFβ). Thus, Psi patterns tissue growth by directly repressing transcription of developmental growth suppressors. Analysis of direct Psi targets identified novel growth inhibitors, includingTolkin(Zinc metallopeptidase implicated in TGFβ signalling),Ephexin(Rho-GEF) andemp(CD36 scavenger receptor-related protein). Their depletion not only suppressed impaired growth associated with Psi knockdown, but alone was sufficient to drive wing overgrowth. Thus, Psi drives wing growth twofold, through direct activation ofMycand through transcriptional repression of growth inhibitors comprising core developmental pathways.
Patient DNA cross-reactivity of the CDC SARS-CoV-2 extraction control leads to an inherent potential for false negative results
Authors: Rosebrock Adam P.
Published: May 2020

Testing for RNA viruses such as SARS-CoV-2 requires careful handling of inherently labile RNA during sample collection, clinical processing, and molecular analysis. Tests must include fail-safe controls that affirmatively report the presence of intact RNA and demonstrate success of all steps of the assay. A result of “no virus signal” is insufficient for clinical interpretation: controls must also say “The reaction worked as intended and would have found virus if present.” Unfortunately, a widely used test specified by the US Centers for Disease Control and Prevention (CDC) incorporates a control that does not perform as intended and claimed. Detecting SARS-CoV-2 with this assay requires both intact RNA and successful reverse transcription. The CDC-specified control does not require either of these, due to its inability to differentiate human genomic DNA from reverse-transcribed RNA. Patient DNA is copurified from nasopharyngeal swabs during clinically-approved RNA extraction and is sufficient to return an “extraction control success” signal using the CDC design. As such, this assay fails-unsafe: truly positive patient samples return a false-negative result of “no virus detected, control succeeded” following any of several readily-encountered mishaps. This problem affects tens-of-millions of patients worth of shipped assays, but many of these flawed reagents have not yet been used. There is an opportunity to improve this important diagnostic tool. As demonstrated here, a re-designed transcript-specific control correctly monitors sample collection, extraction, reverse transcription, and qPCR detection. This approach can be rapidly implemented and will help reduce truly positive patients from being incorrectly given the all-clear.

One Sentence Summary

A widely-used COVID-19 diagnostic is mis-designed and generates false-negative results, dangerously confusing “No” with “Don’t know” – but it’s fixable
Using singleton densities to detect recent selection inBos taurus
Authors: Hartfield Matthew , Poulsen Nina Aagaard , Guldbrandtsen Bernt , Bataillon Thomas
Published: May 2020

Many quantitative traits are subject to polygenic selection, where several genomic regions undergo small, simultaneous changes in allele frequency that collectively alter a phenotype. The widespread availability of genome data, along with novel statistical techniques, has made it easier to detect these changes. We apply one such method, the ‘Singleton Density Score’, to the Holstein breed ofBos taurusto detect recent selection (arising up to around 740 years ago). We identify several genes as candidates for targets of recent selection, including some relating to cell regulation, catabolic processes, neural-cell adhesion and immunity. We do not find strong evidence that three traits that are important to humans – milk protein content, milk fat content, and stature – have been subject to directional selection. Simulations demonstrate that sinceB. taurusrecently experienced a population bottleneck, singletons are depleted so the power of SDS methods are reduced. These results inform on which genes underlie recent genetic change inB. taurus, while providing information on how polygenic selection can be best investigated in future studies.

Impact statement

Many traits of ecological or economic importance (including height, disease propensity, climatic adaptation) are ‘polygenic’. That is, they are affected by a large number of genetic variants, with each one only making a small contribution to a trait, but collectively influence variation. As selection acts on all of these variants simultaneously, it only changes the frequency of each one by a small amount, making it hard to detect such selection from genome data. This situation has changed in recent years, with the proliferation of whole–genome data from many individuals, along with the development of methods to detect the subtle effects of polygenic selection. Here, we use data from 102 genomes from domesticated cattle (Bos taurus) that has experienced intense artificial selection since domestication, and test whether we can detect signatures of recent selection (arising up to 740 years ago). Domesticated species are appealing for this kind of study, as they are subject to extensive genome sequencing studies, and genetic variants can be related to traits under selection. We carried out our analysis in two parts. We first performed a genome–wide scan to find individual genetic regions that show signatures of recent selection. We identify some relating to cell regulation, catabolic processes, neural-cell adhesion and immunity. In the second part, we then analysed genetic regions associated with three key traits: milk protein content, milk fat content, and stature. We tested whether these regions collectively showed a signature of selection, but did not find a significant result in either case. Simulations suggest that the domestication history of cattle affected the power of these methods. We end with a discussion on how to best detect polygenic selection in future studies.
A colorimetric comparison of sunless with natural skin tan
Authors: Amano Kinjiro , Xiao Kaida , Wuerger Sophie , Meyer Georg
Published: May 2020

The main ingredient of sunless tanning products is dihydroxyacetone (DHA). DHA reacts with the protein and amino acid composition in the surface layers of the skin, producing melanoidins, which changes the skin colour, imitating natural skin tan caused by melanin. The purpose of this study was to characterise DHA-induced skin colour changes and to test whether we can predict the outcome of DHA application on skin tone changes.

To assess the DHA-induced skin colour shift quantitatively, colorimetric and spectral measurements of the inner forearm were obtained before, four hours and 24 hours after application of a 7.5% concentration DHA gel in the experimental group (n= 100). In a control group (n= 60), the same measurements were obtained on both the inner forearm (infrequently sun-exposed) and the outer forearm (frequently sun-exposed); the difference between these two areas was defined as the naturally occurring tan. Skin colour shifts caused by DHA tanning and by natural tanning were compared in terms of lightness (L*), redness (a*) and yellowness (b*) in the standard CIELAB colour space. Naturalness of the DHA-induced skin tan was evaluated by comparing the trajectory of the chromaticity distribution in (L*,b*) space with that of naturally occurring tan. Twenty-four hours after DHA application, approximately 20% of the skin colour samples became excessively yellow, with chromaticities outside the natural range in (L*,b*) space. A principal component analysis was used to characterise the tanning pathway. Skin colour shifts induced by DHA were predicted by a multiple regression on the chromaticities and the skin properties. The model explained up to 49% of variance in colorimetric components with a median error of less than 2 ΔE. We conclude that the control of both the magnitude and the direction of the colour shift is a critical factor to achieve a natural appearance.
Once delayed non-invasive remote ischemic preconditioning protects against early stroke by modulating neuroinflammatory responses in rats
Authors: Du Xiangnan , Yang Jian , Zhao Yanlong , Wang Xuemei , Geng Xiaokun
Published: May 2020

Once delayed non-invasive remote ischemic preconditioning (RIPC) has been proven to provide endogenous protection against injury induced by ischemia–reperfusion in the central nervous system. However, for thus ischemic preconditioning method, it is still unclear how long this protection can maintain and what the underlying mechanism is. In this study, we tested the hypothesis that once delayed non-invasive RIPC protects brain injury at short reperfusion time. The rat was stimulated by transient middle cerebral artery occlusion (MCAo) for 90 min, and subsequent reperfusion was performed at 6 h, 72 h and 7 days after MCAo. RIPC was conducted in both hind limbs 24 h before MCAo for 3 cycles (10 min ischemia/ 10 min reperfusion). The infarct size was measured by 2, 3, 5-triphenyl-2H-tetrazolium chloride (TTC) staining and Cresyl violet (CV) staining. The mRNA and protein levels of inflammatory cytokines in the brain were measured by real-time RT-PCR and ELISA. The results showed that once delayed non-invasive RIPC reduced the infarct size, improved neurological functions and behavioral performance at 6 and 72 h post-stroke. There was no change by reperfusion at 7 d after MCAo. RIPC reduced the levels of TNFα, IL-1β and IL-6 in the brain at 72 h post stroke. It also reduced the levels of TNFα and IL-1β when reperfusion at 6 h after MCAo. Our results strongly supported that once delayed non-invasive RIPC protects against stroke as a non-invasive neuroprotective strategy, which maintained for both short and middle term ischemic reperfusion time. The protective effect is mediated by the modulation of inflammatory response in the ischemic brain.
Dermomyotome-derived endothelial cells migrate to the dorsal aorta to support hematopoietic stem cell emergence
Authors: Sahai-Hernandez Pankaj , Pouget Claire , Svoboda Ondřej , Traver David
Published: May 2020

Development of the dorsal aorta is a key step in the establishment of the adult blood-forming system, since hematopoietic stem and progenitor cells (HSPCs) arise from ventral aortic endothelium in all vertebrate animals studied. Work in zebrafish has demonstrated that arterial and venous endothelial precursors arise from distinct subsets of lateral plate mesoderm. Earlier studies in the chick showed that paraxial mesoderm generates another subset of endothelial cells that incorporate into the dorsal aorta to replace HSPCs as they exit the aorta and enter circulation. Here we show that a similar process occurs in the zebrafish, where a population of endothelial precursors delaminates from the somitic dermomyotome to incorporate exclusively into the developing dorsal aorta. Whereas somite-derived endothelial cells (SDECs) lack hematopoietic potential, they act as local niche to support the emergence of HSPCs from neighboring hemogenic endothelium. Thus, at least three subsets of endothelial cells (ECs) contribute to the developing dorsal aorta: vascular ECs, hemogenic ECs, and SDECs. Taken together, our findings indicate that the distinct spatial origins of endothelial precursors dictate different cellular potentials within the developing dorsal aorta.
Delayed effect of drought on the xylem vulnerability to cavitation inFagus sylvaticaL
Authors: Herbette Stephane , Charrier Olivia , cochard Hervé , Barigah Têté Severien
Published: May 2020

Knowledge on variations of drought resistance traits is needed to predict the potential of trees to adapt to severe drought events expected to be more intense and frequent. Xylem vulnerability to cavitation is among the most important traits related to drought-induced mortality and exhibits a large variability between species. Acclimation of this trait to environmental conditions implies changes in the xylem structure and organization, leading previous studies to investigate its variations under conditions preserving growth. In European beech saplings, we assessed the effect of droughts of on the vulnerability to cavitation in branches that develop during recovery. The newly formed branches displayed lower vulnerability to cavitation in the plants that underwent the severest droughts leading to native embolism; the pressure that induces 50% loss of conductance being of −3.98 MPa in severely droughted plants whereas it was of −3.1 MPa in control plants, respectively. Although unexpected, these results argue for an acclimation, and not a weakening, of this trait to drought events.

Key message

severe water stress make the future developed shoots less vulnerable to xylem cavitation.
Structure-function properties in disordered condensates
Authors: Bhandari Kamal , Cotten Michael A. , Kim Jonggul , Rosen Michael K. , Schmit Jeremy D.
Published: May 2020

Biomolecular condensates appear throughout the cell serving a wide variety of functions. Many condensates appear to form by the assembly of multivalent molecules, which produce phase separated networks with liquid-like properties. These networks then recruit client molecules, with the total composition providing functionality. Here we use a model system of poly-SUMO and poly-SIM proteins to understand client-network interactions and find that the structure of the network plays a strong role in defining client recruitment, and thus functionality. The basic unit of assembly in this system is a zipper-like filament composed of alternating poly-SUMO and poly-SIM molecules. These filaments have defects of unsatisfied bonds that allow for both the formation of a 3D network and the recruitment of clients. The filamentous structure constrains the scaffold stoichiometries and the distribution of client recruitment sites that the network can accommodate. This results in a non-monotonic client binding response that can be tuned independently by the client valence and binding energy. These results show how the interactions within liquid states can be disordered yet still contain structural features that provide functionality to the condensate.
dms-view: Interactive visualization tool for deep mutational scanning data
Authors: Hilton Sarah K. , Huddleston John , Black Allison , North Khrystyna , Dingens Adam S. , Bedford Trevor , Bloom Jesse D.
Published: May 2020

Summary and Purpose

The high-throughput technique of deep mutational scanning (DMS) has recently made it possible to experimentally measure the effects of all amino-acid mutations to a protein (Fowler and Fields 2014). Over the past five years, this technique has been used to study dozens of different proteins (Esposito et al. 2019) and answer a variety of research questions. For example, DMS has been used for protein engineering (Wrenbeck, Faber, and Whitehead 2017), understanding the human immune response to viruses (Lee et al. 2019), and interpreting human variation in a clinical setting (Starita et al. 2017; Gelman et al. 2019). Accompanying this proliferation of DMS studies has been the development of software tools (Bloom 2015; Rubin et al. 2017) and databases (Esposito et al. 2019) for data analysis and sharing. However, for many purposes it is important to also integrate and visualize the DMS data in the context of other information, such as the 3-D protein structure or natural sequence-variation data.

Here we describedms-view(https://dms-view.github.io/), a flexible, web-based, interactive visualization tool for DMS data.dms-viewis written in JavaScript and D3, and links site-level and mutation-level DMS data to a 3-D protein structure. The user can interactively select sites of interest to examine the DMS measurements in the context of the protein structure.dms-viewtracks the input data and user selections in the URL, making it possible to save specific views of interactively generated visualizations to share with collaborators or to support a published study. Importantly,dms-viewtakes a flexible input data file so users can easily visualize their own DMS data in the context of protein structures of their choosing, and also incorporate additional information such amino-acid frequencies in natural alignments.
Crystal structures of a series of bis(acetylacetonato)oxovanadium(IV) complexes containing N-donor pyridyl ligands
Authors: Rood Jeffrey A. , Reehl Steven R. , Jacoby Kaitlyn A. , Oliver Allen
Published: May 2020

Crystal structures for a series of bis(acetylacetonato)oxovanadium(IV) complexes containing N-donor pyridyl ligands are reported, namely, bis(acetylacetonato-κ2
O,O′)oxido(pyridine-κN)vanadium(IV), [V(C5H7O2)2O(C5H5N)], 1, bis(acetylacetonato-κ2
O,O′)oxido(pyridine-4-carbonitrile-κN)vanadium(IV), [V(C5H7O2)2O(C6H4N2)], 2, and bis(acetylacetonato-κ2
O,O′)(4-methoxypyridine-κN)oxidovanadium(IV), [V(C5H7O2)2O(C6H7NO)], 3, Compounds 1–3 have the formulae VO(C5H7O2)2
L, where L = pyridine (1), 4-cyano-pyridine (2), and 4-methoxypyridine (3). Compound 1 was previously reported [Meicheng et al. (1984). Kexue Tongbao, 29, 759–764 and DaSilva, Spiazzi, Bortolotto & Burrow (2007). Acta Crystallogr., E63, m2422] and redetermined here at cryogenic temperatures. Compounds 1 and 2 as pyridine and 4-cyanopyridine adducts, respectively, crystallize as distorted octahedral structures with the oxo and pyridyl ligands trans to one another. A crystallographic twofold axis runs through the O—V—N bonds. Compound 3 containing a 4-methoxypyridine ligand crystallizes as a distorted octahedral structure with the oxo and pyridyl ligands cis to one other, removing the twofold symmetry seen in the other complexes.
fac-Triaqua(1,10-phenanthroline-κ2N,N′)(sulfato-κO)cobalt(II): crystal structure, Hirshfeld surface analysis and computational study
Authors: Setifi Zouaoui , Kwong Huey Chong , Tiekink Edward R. T. , Maris Thierry , Setifi Fatima
Published: May 2020

The CoIIatom in the title complex, [Co(SO4)(C12H8N2)(H2O)3] (or C12H14CoN2O7S), is octahedrally coordinated within a cis-N2O4donor set defined by the chelating N-donors of the 1,10-phenanthroline ligand, sulfate-O and three aqua-O atoms, the latter occupying an octahedral face. In the crystal, supramolecular layers lying parallel to (110) are sustained by aqua-O—H...O(sulfate) hydrogen bonding. The layers stack along thec-axis direction with the closest directional interaction between them being a weak phenanthroline-C—H...O(sulfate) contact. There are four significant types of contact contributing to the calculated Hirshfeld surface: at 44.5%, the major contribution comes from O—H...O contacts followed by H...H (28.6%), H...C/C...H (19.5%) and C...C (5.7%) contacts. The dominance of the electrostatic potential force in the molecular packing is also evident in the calculated energy frameworks. The title complex is isostructural with its manganese, zinc and cadmium containing analogues and isomeric with itsmer-triaqua analogue.
The crystal structure of a new CdTe2O5polymorph, isotypic with ∊-CaTe2O5
Authors: Eder Felix , Weil Matthias
Published: May 2020

Single crystals of cadmium pentaoxidoditellurate(IV), CdTe2O5, were obtained as by-products in a hydrothermal reaction of Cd(NO3)2·4H2O, TeO2, H6TeO6and NH3(molar ratios 2:1:1:6) at 483 K for seven days. The crystals represent a different polymorph (henceforth referred to as theβ-form) than theα-CdTe2O5crystals grown from the melt, and are isotypic with hydrothermally grown∊-CaTe2O5. The asymmetric unit ofβ-CdTe2O5comprises one Cd, two Te and five O sites, all of which are located in general positions (Wyckoff position 4e). The cadmium(II) atom is coordinated by seven oxygen atoms, forming2∞[CdO6/2O1/1] (100) layers. Both tellurium sites are surrounded by four oxygen atoms with one of them being at a significantly longer distance than the other three. The resulting bisphenoidal [TeO4] units also form layers propagating parallel to (100) by sharing edges with each other. The stereochemically active 5s2lone pair of the TeIVatoms leads to the formation of large channels extending along [011] and smaller ones along [010]. A quantitative comparison between the crystal structures ofβ-CdTe2O5and ∊-CaTe2O5is made.
Tunisian National Innovation System futures: an actors’ analysis focus
Authors: Chaabouni Refaat , Bouzaiane Lotfi
Published: May 2020

Purpose

This paper aims to focus on the Tunisian National Innovation System (NIS) and the conditions that might foster its aptitude to support socio-economic transformation.

Design/methodology/approach

The paper adopts an original twofold foresight methodology combining the analysis of key players with the exploration of scenarios. While usually, a foresight exercise considers only one of these two futures studies approaches.

Findings

The “Dynamic Islands System” scenario reflects the present situation and current trends. It shows that all expected components of an efficient system are in place, but they are evolving more or less independently. “Connected System” is the most desirable option because it reflects the potential to improve strongly productivity, competitiveness and social inclusion. The “Dislocated System” is a third possible but risky scenario. Despite the interesting insights provided through futures imaging, the scenario approach is not sufficient in providing indications of how and which actors can make happen the changes needed to move towards the desired state. So, a second step of the adopted twofold foresight approach addresses the role of key players. The analysis aims to reveal which actors are in a position to implement the required changes and thereby support the transition from the present to the desired scenario.

Practical implications

The challenges ahead are then pointed out, namely, that the private sector and firms would have to take the lead in the future; and that the less influential players would have to work side by side to be able to direct the NIS to the “Connected scenario”.

Originality/value

The clue in this approach is to transform a sub-optimal reality to achieve a desired end-state by understanding the trend scenario. The actors’ analysis helps to clarify the respective attitudes and concerns of the players vis-à-vis the required changes. In this two-step foresight approach, the desired scenario is considered as a specific project.