bluuebunny/crossref_metadata_2025 huggingface dataset:
Biologging of emperor penguins – attachment techniques and associated deployment performance
Authors: Houstin Aymeric , Zitterbart Daniel P. , Winterl Alexander , Richter Sebastian , Planas-Bielsa Víctor , Chevallier Damien , Ancel André , Fournier Jérôme , Fabry Ben , Le Bohec Céline
Published: June 2021

An increasing number of marine animals are equipped with biologgers, to study their physiology, behaviour and ecology, often for conservation purposes. To minimise the impacts of biologgers on the animals’ welfare, theRefinementprinciple from the Three Rs framework (Replacement, Reduction, Refinement) urges to continuously test and evaluate new and updated biologging protocols.

Here, we propose alternative and promising techniques for emperor penguin (Aptenodytes forsteri) capture and on-site logger deployment that aim to mitigate the potential negative impacts of logger deployment on these birds. We equipped adult emperor penguins for short-term (GPS, Time-Depth Recorder (TDR)) and long-term (i.e. planned for one year) deployments (ARGOS platforms, TDR), as well as juvenile emperor penguins for long-term deployments (ARGOS platforms) in the Weddell Sea area where they had not yet been studied.

We describe and qualitatively evaluate our protocols for the attachment of biologgers on-site at the colony, the capture of the animals and the recovery of the devices after deployment. We report unprecedented recaptures of long-term equipped adult emperor penguins (50% of equipped individuals recaptured after 290 days). Our data demonstrate that the traditional technique of long-term attachment by gluing the biologgers directly to the back feathers is detrimental to the birds. It causes excessive feather breakage and the loss of the devices at an early stage. We therefore propose an alternative method of attachment for back-mounted devices. This technique led to successful year-round deployments on 37.5% of the equipped juveniles. Finally, we also disclose the first deployments of leg-bracelet mounted TDRs on emperor penguins.

Our findings highlight the importance of monitoring potential impacts of biologger deployments on the animals and the need to remain critical towards established and new protocols.
The interactome of site-specifically acetylated linker histone H1
Authors: Höllmüller Eva , Greiner Katharina , Kienle Simon M. , Scheffner Martin , Marx Andreas , Stengel Florian
Published: June 2021

Linker histone H1 plays a key role in chromatin organization and maintenance, yet our knowledge of the regulation of H1 functions by posttranslational modifications (PTMs) is rather limited. In this study, we report on the generation of site-specifically mono- and di-acetylated linker histone H1.2 by genetic code expansion. We used these modified histones to identify and characterize the acetylation-dependent cellular interactome of H1.2 by affinity purification-mass spectrometry (AP-MS) and show that site-specific acetylation results in overlapping, but distinct groups of interacting partners. Among these, we find multiple translational initiation factors and transcriptional regulators such as the NAD+-dependent deacetylase SIRT1, which we demonstrate to act on acetylated H1.2. Taken together our data suggests that site-specific acetylation of H1.2 plays a role in modulating protein-protein interactions.
Cuticular Wax Composition is Essential for Plant Recovery Following Drought with Little Effect under Optimal Conditions
Authors: Negin Boaz , Hen-Avivi Shelly , Almekias-Siegl Efrat , Shachar Lior , Aharoni Asaph
Published: June 2021

Despite decades of extensive study, the role of cuticular lipids in sustaining plant fitness is far from being understood. To answer this fundamental question, we employed genome editing in tree tobacco (Nicotiana glauca) plants and generated mutations in 16 different cuticular lipids-related genes. We chose tree tobacco due to the abundant, yet simply composed epicuticular waxes deposited on its surface. Five out of 9 different mutants that displayed a cuticular lipids-related phenotype were selected for in depth analysis. They had either reduced total wax load or complete deficiency in certain wax components. This led to substantial modification in surface wax crystal structure and to elevated cuticular water loss. Remarkably, under non-stressed conditions, mutant plants with altered wax composition did not display elevated transpiration or reduced growth. However, once exposed to drought, plants lacking alkanes were not able to strongly reduce their transpiration, leading to leaf death and impaired recovery upon resuscitation, and even to stem cracking, a phenomenon typically found in trees experiencing drought stress. In contrast, plants deficient in fatty alcohols exhibited an opposite response, having reduced cuticular water loss and rapid recovery following drought. This differential response was part of a larger trend, of no common phenotype connecting plants with a glossy appearance. We conclude that alkanes are essential under drought response and much less under normal non-stressed conditions, enabling plants to seal their cuticle upon stomatal closure, reducing leaf death and facilitating a speedy recovery.
Modelling interference between vectors of non-persistently transmitted plant viruses to identify effective control strategies
Authors: Zaffaroni Marta , Rimbaud Loup , Mailleret Ludovic , Cunniffe Nik J. , Bevacqua Daniele
Published: June 2021

Aphids are the primary vector of plant viruses. Transient aphids, which probe several plants per day, are considered to be the principal vectors of non-persistently transmitted (NPT) viruses. However, resident aphids, which can complete their life cycle on a single host and are affected by agronomic practices, can transmit NPT viruses as well. Moreover, they can interfere both directly and indirectly with transient aphids, eventually shaping plant disease dynamics. By mean of an epidemiological model, originally accounting for ecological principles and agronomic practices, we explore the consequences of fertilization and irrigation, pesticide deployment and roguing of infected plants on the spread of viral diseases in crops. Our results indicate that the spread of NPT viruses can be i) both reduced or increased by fertilization and irrigation, depending on whether the interference is direct or indirect; ii) counter-intuitively increased by pesticide application and iii) reduced by roguing infected plants. We show that a better understanding of vectors’ interactions would enhance our understanding of disease transmission, supporting the development of disease management strategies.

Author summary

A range of both experimental and theoretical studies show that the behaviour and population dynamics of insects depend strongly upon interactions with other insect species. These interactions have the potential to greatly affect the dynamics of insect-vectored plant disease, as transmission of viruses is intimately dependent on the local density of vectors, as well as how they select and move between potential host plants. Surprisingly, the effects of interaction between vector species on epidemics remains little studied and even worse understood, probably because experimentation is costly and difficult. Here, we present a model which permits to investigate the effect of interaction between a virus, two vector species, and the host plant on the spread of viral disease in crops. In this study, our model is used to explore the consequences of common agronomic practices on epidemics. Our study highlights the importance of exploring vectors’ interactions to enhance the understanding of disease transmission, supporting the development of disease management strategies.
The rapid developmental rise of somatic inhibition disengages hippocampal dynamics from self-motion
Authors: Dard Robin F. , Leprince Erwan , Denis Julien , Rao-Balappa Shrisha , Suchkov Dmitrii , Boyce Richard , Lopez Catherine , Giorgi-Kurz Marie , Szwagier Tom , Dumont Theo , Rouault Hervé , Minlebaev Marat , Baude Agnes , Cossart Rosa , Picardo Michel A.
Published: June 2021

Early electrophysiological brain oscillations recorded in preterm babies and newborn rodents are initially mostly ignited by bottom-up sensorimotor activity and only later can detach from external inputs. This is a hallmark of most developing brain areas including the hippocampus, which in the adult brain, functions in integrating external inputs onto internal dynamics. Such developmental disengagement from external inputs is likely a fundamental step for the proper development of cognitive internal models. Despite its importance, the developmental timeline and circuit basis for this disengagement remain unknown. To address this issue, we have investigated the daily evolution of CA1 dynamics and underlying circuits during the first two postnatal weeks of mouse development using two-photon calcium imaging in non-anesthetized pups. We show that the first postnatal week ends with an abrupt shift in the representation of self-motion in CA1. Indeed, most CA1 pyramidal cells switch from activated to inhibited by self-generated movements at the end of the first postnatal week whereas the majority of GABAergic neurons remain positively modulated throughout this period. This rapid switch occurs within two days and follows the rapid anatomical and functional surge of local somatic GABAergic innervation. The observed change in dynamics is consistent with a two-population model undergoing a strengthening of inhibition. We propose that this abrupt developmental transition inaugurates the emergence of internal cognitive models.
Distinguishing between models of mammalian gene expression: telegraph-like models versus mechanistic models
Authors: Braichenko Svitlana , Holehouse James , Grima Ramon
Published: June 2021

Two-state models (telegraph-like models) have a successful history of predicting distributions of cellular and nascent mRNA numbers that can well fit experimental data. These models exclude key rate limiting steps, and hence it is unclear why they are able to accurately predict the number distributions. To answer this question, here we compare these models to a novel stochastic mechanistic model of transcription in mammalian cells that presents a unified description of transcriptional factor, polymerase and mature mRNA dynamics. We show that there is a large region of parameter space where the first, second and third moments of the distributions of the waiting times between two consecutively produced transcripts (nascent or mature) of two-state and mechanistic models exactly match. In this region, (i) one can uniquely express the two-state model parameters in terms of those of the mechanistic model, (ii) the models are practically indistinguishable by comparison of their transcript numbers distributions, and (iii) they are distinguishable from the shape of their waiting time distributions. Our results clarify the relationship between different gene expression models and identify a means to select between them from experimental data.
Deep learning-based brain transcriptomic signatures associated with the neuropathological and clinical severity of Alzheimer’s disease
Authors: Wang Qi , Chen Kewei , Su Yi , Reiman Eric M. , Dudley Joel T. , Readhead Benjamin
Published: June 2021

Brain tissue gene expression from donors with and without Alzheimer’s disease (AD) have been used to help inform the molecular changes associated with the development and potential treatment of this disorder. Here, we use a deep learning method to analyze RNA-seq data from 1,114 brain donors from the AMP-AD consortium to characterize post-mortem brain transcriptome signatures associated with amyloid-β plaque, tau neurofibrillary tangles, and clinical severity in multiple AD dementia populations. Starting from the cross-sectional data in the ROSMAP cohort (n = 634), a deep learning framework was built to obtain a trajectory that mirrors AD progression. A severity index (SI) was defined to quantitatively measure the progression based on the trajectory. Network analysis was then carried out to identify key gene (index gene) modules present in the model underlying the progression. Within this dataset, SIs were found to be very closely correlated with all AD neuropathology biomarkers (R ∼ 0.5, p < 1e-11) and global cognitive function (R = -0.68, p < 2.2e-16). We then applied the model to additional transcriptomic datasets from different brain regions (MAYO, n = 266; MSBB, n = 214), and observed that the model remained significantly predictive (p < 1e-3) of neuropathology and clinical severity. The index genes that significantly contributed to the model were integrated with AD co-expression regulatory networks, resolving four discrete gene modules that are implicated in vascular and metabolic dysfunction in different cell types respectively. Our work demonstrates the generalizability of this signature to frontal and temporal cortex measurements and additional brain donors with AD, other age-related neurological disorders and controls; and revealed the transcriptomic network modules contribute to neuropathological and clinical disease severity. This study illustrates the promise of using deep learning methods to analyze heterogeneous omics data and discover potentially targetable molecular networks that can inform the development, treatment and prevention of neurodegenerative diseases like AD.
Sequential delay and probability discounting tasks in mice reveal anchoring effects partially attributable to decision noise
Authors: Rojas Gerardo R. , Curry-Pochy Lisa S. , Chen Cathy S. , Heller Abigail T. , Grissom Nicola M.
Published: June 2021

Delay discounting and probability discounting decision making tasks in rodent models have high translational potential. However, it is unclear whether the discounted value of the large reward option is the main contributor to variability in animals’ choices in either task, which may limit translatability to human discounting data. Male and female mice underwent sessions of delay and probability discounting in sequence to assess how choice behavior adapts over experience with each task. To control for “anchoring” (persistent choices based on the initial delay or probability), mice experienced “Worsening” schedules where the large reward was offered under initially favorable delay or probability conditions that became less favorable during testing, followed by “Improving” schedules where the large reward was offered under initially unfavorable conditions that improved over a session. During delay discounting, both male and female mice showed elimination of anchoring effects over training. In probability discounting, both sexes of mice continued to show some anchoring even after months of training. One possibility is that noisy action selection could contribute to these anchoring effects, rather than persistent fluctuations in value discounting. We fit choice behavior in individual animals using models that included both a value-based discounting parameter and a decision noise parameter that captured variability in choices deviating from value maximization. Changes in anchoring behavior over time were tracked by changes in our decision noise parameter, not the value parameter. Thus, changes in discounting behavior in mice can result from changes in exploration of the environment rather than changes in reward valuation.
Escaping through the predator’s gill cleft: A defensive tactic of juvenile eels after capture by predatory fish
Authors: Hasegawa Yuha , Yokouchi Kazuki , Kawabata Yuuki
Published: June 2021

Some prey animals can actively escape from predators even after being captured, but knowledge of such behaviors is still limited, especially in vertebrates. Here, we report the unique active escape behavior of Japanese eel Anguilla japonica juveniles through the gill cleft of the predatory fish Odontobutis obscura. Of the 54 A. japonica juveniles captured by the predator, 28 escaped via the predator’s gill, and most escaped individuals survived afterwards. In all escaped individuals, their tails emerged first from the gill cleft of the predator, and then their whole bodies slipped out in a backward direction from the cleft. These findings indicate that A. japonica juveniles have the specialized antipredator tactic, which provides the basis for further investigation from behavioral, ecological, and evolutionary perspectives.
Identification of the CoA-ester intermediates and genes involved in the cleavage and degradation of the steroidal C-ring by Comamonas testosteroni TA441
Authors: Horinouchi Masae , Hayashi Toshiaki
Published: June 2021

Comamonas testosteroni TA441 degrades steroids aerobically via aromatization of the A-ring accompanied by B-ring cleavage, followed by D- and C-ring cleavage. We previously revealed major enzymes and intermediate compounds in A,B-ring cleavage, β-oxidation cycle of the cleaved B-ring, and partial C,D-ring cleavage process. Here, we elucidated the C-ring cleavage and the β-oxidation cycle that follows. ScdL1L2, a 3-ketoacid Coenzyme A (CoA) transferase which belongs to the SugarP_isomerase superfamily, was thought to cleave the C-ring of 9-oxo-1,2,3,4,5,6,10,19-octanor-13,17-secoandrost-8(14)-ene-7,17-dioic acid-CoA ester, the key intermediate compound in the degradation of 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oic acid (3aα-H-4α [3′-propionic acid]-7aβ-methylhexahydro-1,5-indanedione; HIP)-CoA ester in the previous study; however, this study suggested that ScdL1L2 is the isomerase of the derivative with a hydroxyl group at C-14 which cleaves C ring. The subsequent ring-cleaved product was indicated to be converted to 4-methyl-5-oxo-octane-1,8-dioic acid-CoA ester mainly by ORF33-encoded CoA-transferase (named ScdJ), followed by dehydrogenation by ORF21 and 22-encoded acyl-CoA dehydrogenase (named ScdM1M2). Then a water molecule is added by ScdN for further degradation by β-oxidation. ScdN is considered to catalyze the last reaction in C,D-ring degradation by the enzymes encoded in the steroid degradation gene cluster tesB to tesR.

IMPORTANCE

Studies on bacterial steroid degradation were initiated more than 50 years ago primarily to obtain materials for steroid drugs. Steroid-degrading bacteria are globally distributed, and the role of bacterial steroid degradation in the environment as well as in human is attracting attention. The overall degradation of steroidal four rings is proposed, however there are still much to be revealed to understand the complete degradation pathway. This study aims to uncover the whole steroid degradation process in C. testosteroni, which is one of the most studied representative steroid degrading bacteria and is suitable for exploring the degradation pathway because the involvement of degradation-related genes can be determined by gene disruption.
Single Cell Raman-Deuterium Isotope Probing for Drug Resistance of Elizabethkingia spp
Authors: Yuan Shuying , Chen Yanwen , Song Yizhi , Zou Lin , Lin Kaicheng , Lu Xinrong , Liu Ruijie , Zhang Shaoxing , Shen Danfeng , Song Zhenju , Tong Chaoyang , Chen Li , Sun Guiqin
Published: June 2021

Nosocomial infection associated with Elizabethkingia spp. is an emerging clinical concern characterized by multi-drug resistance and severe clinical consequences particularly in immunocompromised individuals and infants. Efficient control of this infection demands quick and reliable methods to determine the right drugs for the treatment. In this study, E. meningoseptica ATCC 13253 and four clinical isolates of Elizabethkingia spp. obtained from China, were subjected to single cell Raman spectroscopy analysis coupling with deuterium probing (single cell Raman-DIP). The results demonstrated that single cell Raman-DIP could generate an antimicrobial susceptibility testing result for Elizabethkingia spp. colonies within 4 hours based on their metabolisms variations at single cell level, and the drug resistant spectra of Elizabethkingia spp. determined by single cell Raman-DIP were consistent with the classical MIC method. Meanwhile single cell Raman spectroscopy (single cell RS) was applied to analyze Raman spectra of Elizabethkingia spp., which were revealed that their ratios of nucleic acid/protein were lower than other gram-negative pathogens and isolates from different origins could be distinguished by their Raman fingerprint. The in vitro results confirmed that minocycline and levofloxacin are first-line antimicrobials for Elizabethkingia spp. infection.
Single-cell RNA sequencing uncovers the excitatory/inhibitory synaptic unbalance in the retrosplenial cortex after peripheral nerve injury
Authors: Wang Jing-Hua , Wu Cheng , Lian Yan-Na , Wang Zi-Yue , Dong Jia-jun , Wu Qin , Liu Li , Sun Li , Chen Wei , Chen Wenjuan , Zhang Zhi , Zhuo Min , LI Xiang-Yao
Published: June 2021

Nerve injury in the somatosensory pathway may induce maladaptive changes at the transcriptional or protein level, contributing to the development and maintenance of neuropathic pain. In contrast to the retrosplenial cortex (RSC), which processes nociceptive information and exhibits structural and molecular changes after nerve injury, detailed transcriptional changes in the RSC are not yet known. Here we confirm the involvement of the RSC in regulating pain sensation and observe that the same peripheral stimulation activates more retrosplenial neurons after nerve injury; reducing the activities of CaMKIIα+ splenial cells relieves peripheral pain hypersensitivity after nerve injury. Using a single-cell RNA sequencing (scRNA-seq) approach, we identified cell-type-specific gene expression changes after nerve injury, and the gene set enrichment analysis results revealed suppressed ion homeostasis in CaMKIIα+ neurons. Furthermore, examination of the expression of genes encoding ligand-gated ion channels showed a decrease in Gabar1a but an increase in Gria1 in CaMKIIα+ neurons; consistently, we confirmed the unbalanced excitatory/inhibitory synaptic transmission by using the electrophysiological recording approach. Moreover, micro-infusion of 1-Naphthyl acetyl spermine in the RSC to reduce excitatory synaptic transmission alleviated peripheral pain hypersensitivity. Our data confirm the involvement of the RSC in pain regulation and provide information on cell type-dependent transcriptomic changes after nerve injury, which will contribute to the understanding of the mechanisms mediating neuropathic pain.
Comprehensive profiling of liver x receptor splicing in triple negative breast cancer reveals existence of novel splice variants that are prognostic for survival
Authors: Lianto Priscilia , Moore J. Bernadette , Hughes Thomas A. , Thorne James L.
Published: June 2021

The liver x receptors (LXR) alpha and beta are ligand-responsive transcription factors that link homeostatic control of lipid metabolism with cancer pathophysiology and prognosis. LXR activity is elevated in triple negative breast cancer relative to other breast cancer subtypes, driving gene signatures associated with drug resistance and metastasis. The loci encoding LXRα and LXRβ produce multiple alternatively spliced proteins, but the true range of variants and their relevance to cancer remain poorly defined. Seven splice variants of LXRα or LXRβ were detected. Three have not been recorded previously and five were prognostic. High expression of full length LXRα was associated with shorter disease-free survival but splice variants harbouring truncations of the ligand binding domain were prognostic for improved survival. All LXRβ variants were associated with longer disease-free survival. Mechanistically, while full length LXRα positively correlated with target gene expression in primary samples, LXRβ was inversely correlated. We conclude that canonical LXRα function is an oncogenic driver of triple negative tumour pathophysiology that can be countered by high expression of truncated splice variants and/or full length LXRβ.

Highlights

Expression of full length LXRα is associated with shorter disease-free survival of triple negative breast cancer patients

A systematic evaluation of cell lines and primary tumour samples indicates LXR splicing is extensive in breast cancer

Confirmation of three new LXR splice variants at transcript and protein level

Expression of full length LXRβ or LXRα splice variants that harbour truncated ligand binding domains are associated with better prognosis

Expression of LXR target genes is positively correlated with LXRα in relapsed patients and inversely correlated with LXRβ in survivors.
Placental polyamines regulate acetyl-coA and histone acetylation in a sex-specific manner
Authors: Aye Irving LMH , Gong Sungsam , Avellino Giulia , Barbagallo Roberta , Gaccioli Francesca , Jenkins Benjamin J , Koulman Albert , Murray Andrew J , Charnock-Jones D Stephen , Smith Gordon CS
Published: June 2021

Fetal sex differences play an important role in the pathophysiology of several placenta-related pregnancy complications. We previously reported that the maternal circulating level of a polyamine metabolite was altered in a fetal sex-specific manner, and was associated with pre-eclampsia and fetal growth restriction. Here we show that placental polyamine metabolism is altered in these disorders and that polyamines influence widespread changes in gene expression by regulating the availability of acetyl-CoA which is necessary for histone acetylation. Sex differences in polyamine metabolism are associated with escape from X chromosome inactivation of the gene encoding the enzyme spermine synthase in female placentas, as evidenced by biallelic expression of the gene in female trophoblasts. Polyamine depletion in primary human trophoblasts impairs glycolysis and mitochondrial metabolism resulting in decreased availability of acetyl-CoA and global histone hypoacetylation, in a sex-dependent manner. Chromatin-immunoprecipitation sequencing and RNA–sequencing identifies downregulation of progesterone biosynthetic pathways as a key target and polyamine depletion reduced progesterone release in male trophoblasts. Collectively, these findings suggest that polyamines regulate placental endocrine function through metabolic regulation of gene expression, and that sex differences in polyamine metabolism due to XCI escape may buffer the effects of placental dysfunction in pregnancy disorders.
NanoSpring: reference-free lossless compression of nanopore sequencing reads using an approximate assembly approach
Authors: Meng Qingxi , Chandak Shubham , Zhu Yifan , Weissman Tsachy
Published: June 2021

The amount of data produced by genome sequencing experiments has been growing rapidly over the past several years, making compression important for efficient storage, transfer and analysis of the data. In recent years, nanopore sequencing technologies have seen increasing adoption since they are portable, real-time and provide long reads. However, there has been limited progress on compression of nanopore sequencing reads obtained in FASTQ files since most existing tools are either general-purpose or specialized for short read data.

We present NanoSpring, a reference-free compressor for nanopore sequencing reads, relying on an approximate assembly approach. We evaluate NanoSpring on a variety of datasets including bacterial, metagenomic, plant, animal, and human whole genome data. For recently basecalled high quality nanopore datasets, NanoSpring, which focuses only on the base sequences in the FASTQ file, uses just 0.35-0.65 bits per base which is 3-6x lower than general purpose compressors like gzip. NanoSpring is competitive in compression ratio and compression resource usage with the state-of-the-art tool CoLoRd while being significantly faster at decompression. NanoSpring is available on GitHub athttps://github.com/qm2/NanoSpring.
Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor
Authors: Wang Yue , Guo Shimeng , Zhuang Youwen , Yun Ying , Xu Peiyu , He Xinheng , Guo Jia , Yin Wanchao , Xu H. Eric , Xie Xin , Jiang Yi
Published: June 2021

Ghrelin, also called “the hunger hormone”, is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward cognition, learning and memory. One unique feature of ghrelin is its acylation, primarily with an octanoic acid, which is essential for its binding and activation of the ghrelin receptor, a G protein-coupled receptor. The multifaceted roles of ghrelin make ghrelin receptor a highly attractive drug target for growth retardation, obesity, and metabolic disorders. Here we present two cryo-electron microscopy structures of Gq-coupled ghrelin receptor bound to ghrelin and a synthetic agonist, GHRP-6. Analysis of these two structures reveals a unique binding pocket for the octanoyl group, which guides the correct positioning of the peptide to initiate the receptor activation. Together with mutational and functional data, our structures define the rules for recognition of the acylated peptide hormone and activation of ghrelin receptor, and provide structural templates to facilitate drug design targeting ghrelin receptor.
Beyond tracking climate: niche shifts during native range expansion and their implications for novel invasions
Authors: Lustenhouwer Nicky , Parker Ingrid M.
Published: June 2021

Aim

Although ecological niche models have been instrumental in understanding the widespread species distribution shifts under global change, rapid niche shifts limit model transferability to novel locations or time periods. Niche shifts during range expansion have been studied extensively in invasive species, but may also occur in native populations tracking climate change. We compared niche shifts during both types of range expansion in a Mediterranean annual plant to ask (i) whether the species’ native range expansion tracked climate change, (ii) whether further range expansion was promoted by niche expansion, and (iii) how these results changed forecasts of two ongoing invasions in Australia and California.

Location

Eurasian Holarctic, California and Australia

Taxon

Dittrichia graveolens (L.) Greuter (Asteraceae)

Methods

Niche shifts were quantified in both environmental and geographic space, using the framework of niche centroid shift, overlap, unfilling, and expansion (COUE) as well as Maximum Entropy modelling. We used the historic native distribution and climate data (1901-1930) to project the expected distribution in the present climate (1990-2019), and compared it to the observed current distribution of D. graveolens. Finally, we compared invasion forecasts based on the historic and present native niches.

Results

We found that D. graveolens expanded its native range well beyond what would be sufficient to track climate change, associated with a 5.5% niche expansion towards more temperate climates. In contrast, both invasions showed niche conservatism, and were (still) constrained to climatic areas matching the historic native niche.

Main conclusions

our results show that contrary to hypotheses in the literature, niche shifts are not necessarily more rapid in invasions than in native range expansions. We conclude that niche expansion during the process of climate tracking may cause further range expansion than expected based on climate change alone.
Neonicotinoid and pyrethroid combination: A tool to manage insecticide resistance in malaria vectors? Insights from experimental evolution
Authors: Zoh Marius Gonse , Bonneville Jean-Marc , Tutagana Jordan , Laporte Frederic , Fodjo Behi K. , Mouhamadou Chouaibou S. , Sadia Christabel , McBeath Justin , Schmitt Frederic , Horstmann Sebastian , Reynaud Stephane , David Jean-Philippe
Published: June 2021

Background

The introduction of neonicotinoids for managing insecticide resistance in mosquitoes is of high interest as they interact with a biochemical target not previously used in public health. In this concern, Bayer developed a combination of the neonicotinoid clothianidin and the pyrethroid deltamethrin (brand name Fludora® Fusion) as a new vector control tool. Although this combination proved to be efficient against pyrethroid-resistant mosquitoes, its ability to prevent the selection of pyrethroid and neonicotinoid resistance alleles was not investigated. In this context, the objective of this work was to study the dynamics and the molecular mechanisms of resistance ofAn. gambiaeto the separated or combined components of this combination. A field-derivedAn. gambiaeline carrying resistance alleles to multiple insecticides at low frequencies was used as a starting for 33 successive generations of controlled selection. Resistance levels to each insecticide and target site mutation frequencies were monitored throughout the selection process. Cross resistance to other public health insecticides were also investigated. RNA-seq was used to compare gene transcription variations and polymorphisms across all lines.

Results

This study confirmed the potential of this insecticide combination to impair the selection of resistance as compared to its two separated components. Deltamethrin selection led to the rapid enrichment of the kdr L1014F target-site mutation while clothianidin selection led to the over-transcription of multiple cytochrome P450s including some showing high homology with the ones conferring neonicotinoid resistance in other insects. A strong selection signature associated with clothianidin selection was observed on a cytochrome P450 gene cluster previously associated with resistance. Within this cluster, the geneCYP6M1showed the highest selection signature together with a transcription profile supporting a role in clothianidin resistance. Modelling the impact of point mutations selected by clothianidin on CYP6M1 protein structure suggested that the selection of variants affecting its active site can enhance clothianidin metabolism.

Conclusions

In the context of the recent deployment of neonicotinoids for mosquito control and their frequent usage in agriculture, the present study highlights the benefit of combining them with other insecticides for preventing the selection of resistance and sustaining vector control activities.
Thermodynamic genome-scale metabolic modeling of metallodrug resistance in colorectal cancer
Authors: Herrmann Helena A. , Rusz Mate , Baier Dina , Jakupec Michael A. , Keppler Bernhard K. , Berger Walter , Koellensperger Gunda , Zanghellini Jürgen
Published: June 2021

Background

Mass spectrometry-based metabolomics approaches provide an immense opportunity to enhance our understanding of the mechanisms that underpin the cellular reprogramming of cancers. Accurate comparative metabolic profiling of heterogeneous conditions, however, is still a challenge.

Methods

Measuring both intracellular and extracellular metabolite concentrations, we constrain four instances of a thermodynamic genome-scale metabolic model of the HCT116 colorectal carcinoma cell line to compare the metabolic flux profiles of cells that are either sensitive or resistant to ruthenium- or platinum-based treatments with BOLD-100/KP1339 and oxaliplatin, respectively.

Results

Normalizing according to growth rate and normalizing resistant cells according to their respective sensitive controls, we are able to dissect metabolic responses specific to the drug and to the resistance states. We find the normalization steps to be crucial in the interpretation of the metabolomics data and show that the metabolic reprogramming in resistant cells is limited to a select number of pathways.

Conclusions

Here we elucidate the key importance of normalization steps in the interpretation of metabolomics data, allowing us to uncover drug-specific metabolic reprogramming during acquired metal-drug resistance.
Integrative Epigenomic and High-Throughput Functional Enhancer Profiling Reveals Determinants of Enhancer Heterogeneity in Gastric Cancer
Authors: Sheng Taotao , Ho Shamaine Wei Ting , Ooi Wen Fong , Xu Chang , Xing Manjie , Padmanabhan Nisha , Huang Kie Kyon , Ma Lijia , Ray Mohana , Guo Yu Amanda , Leng Sim Ngak , Anene-Nzelu Chukwuemeka George , Chang Mei Mei , Razavi-Mohseni Milad , Beer Michael A. , Foo Roger Sik Yin , Tan Angie Lay Keng , Ong Xuewen , Skanderup Anders Jacobsen , White Kevin P. , Jha Sudhakar , Tan Patrick
Published: June 2021

Background

Enhancers are distal cis-regulatory elements required for cell-specific gene expression and cell fate determination. In cancer, enhancer variation has been proposed as a major cause of inter-patient heterogeneity – however, most predicted enhancer regions remain to be functionally tested.

Results

Analyzing 128 epigenomic histone modification profiles of primary GC samples, normal gastric tissues, and GC cell lines, we report a comprehensive catalog of 75,730 recurrent predicted enhancers, the majority of which are tumor-associated in vivo (>50,000) and associated with lower somatic mutation rates inferred by whole-genome sequencing. Applying Capture-based Self-Transcribing Active Regulatory Region sequencing (CapSTARR-seq) to the enhancer catalog, we observed significant correlations between CapSTARR-seq functional activity and H3K27ac/H3K4me1 levels. Super-enhancer regions exhibited increased CapSTARR-seq signals compared to regular enhancers even when decoupled from native chromatin contexture. We show that combining histone modification and CapSTARR-seq functional enhancer data improves the prediction of enhancer-promoter interactions and pinpointing of germline single nucleotide polymorphisms (SNPs), somatic copy number alterations (SCNAs), and trans-acting TFs involved in GC expression. Specifically, we identified cancer-relevant genes (e.g. ING1, ARL4C) whose expression between patients is influenced by enhancer differences in genomic copy number and germline SNPs, and HNF4α as a master trans-acting factor associated with GC enhancer heterogeneity.

Conclusions

Our study indicates that combining histone modification and functional assay data may provide a more accurate metric to assess enhancer activity than either platform individually, and provides insights into the relative contribution of genetic (cis) and regulatory (trans) mechanisms to GC enhancer functional heterogeneity.
Intrinsic and tumor-induced JAK/STAT signaling regulate developmental timing by the Drosophila prothoracic gland
Authors: Cao Xueya , Pastor-Pareja José Carlos
Published: June 2021

Development involves tightly paced, reproducible sequences of events, yet it must adjust to conditions external to it, such as resource availability and organismal damage. A major mediator of damage-induced immune responses in vertebrates and insects is JAK/STAT signaling. At the same time, JAK/STAT activation by the Drosophila Upd cytokines is pleiotropically involved in normal development of multiple organs. Whether inflammatory and developmental roles of JAK/STAT intersect is unknown. Here, we show that JAK/STAT is active during development of the prothoracic gland (PG), the organ that controls metamorphosis onset through ecdysone production. Reducing JAK/STAT signaling decreased PG size and slightly advanced metamorphosis. Conversely, JAK/STAT hyperactivation, achieved through overexpression of pathway components or SUMOylation loss, caused PG hypertrophy and metamorphosis delay. Interestingly, tissue damage and tumors, known to secrete Upd cytokines, also activated JAK/STAT in the PG and delayed metamorphosis. Finally, we show that expression of transcription factor Apontic, a JAK/STAT target in the PG, recapitulates PG hypertrophy and metamorphosis delay. JAK/STAT damage signaling, therefore, regulates metamorphosis onset at least in part by coopting its developmental role in the PG.

Summary statement

Damage signaling from tumors mediated by JAK/STAT-activating Upd cytokines delays the Drosophila larva-pupa transition through cooption of a JAK/STAT developmental role in the prothoracic gland.
Caveolae respond to acute oxidative stress through membrane lipid peroxidation, cytosolic release of CAVIN1, and downstream regulation of NRF2
Authors: Wu Yeping , Lim Ye-Wheen , Stroud David A. , Martel Nick , Hall Thomas E. , Lo Harriet P. , Ferguson Charles , Ryan Michael T. , McMahon Kerrie-Ann , Parton Robert G.
Published: June 2021

Caveolae have been linked to many biological functions, but their precise roles are unclear. Using quantitative whole cell proteomics of genome-edited cells, we show that the oxidative stress response is the major pathway dysregulated in cells lacking the key caveola structural protein, CAVIN1. CAVIN1 deletion compromised sensitivity to oxidative stress in cultured cells and in animals. Wound-induced accumulation of reactive oxygen species and apoptosis were suppressed in Cavin1-null zebrafish, negatively affecting regeneration. Oxidative stress triggered lipid peroxidation and induced caveolar disassembly. The resulting release of CAVIN1 from caveolae allowed direct interaction between CAVIN1 and NRF2, a key regulator of the antioxidant response, facilitating NRF2 degradation. CAVIN1-null cells with impaired negative regulation of NRF2 showed resistance to lipid peroxidation-induced ferroptosis. Thus, caveolae, via lipid peroxidation and CAVIN1 release, maintain cellular susceptibility to oxidative stress-induced cell death demonstrating a crucial role for this enigmatic organelle in cellular homeostasis and wound response.
Transcranial theta-burst stimulation of primary sensory cortex attenuates somatosensory threat memory in humans
Authors: Ojala Karita E. , Staib Matthias , Gerster Samuel , Ruff Christian C. , Bach Dominik R.
Published: June 2021

Sensory cortices are required for learning to discriminate complex stimuli that predict threat from those that predict safety in rodents. Yet, sensory cortices may not be needed to learn threat associations to simple stimuli. It is unknown whether these findings apply in humans. Here, we investigated the role of primary sensory cortex in discriminative threat conditioning with simple and complex somatosensory conditioned stimuli (CS) in healthy humans. Immediately before conditioning, participants received continuous theta-burst transcranial magnetic stimulation (cTBS) to primary somatosensory cortex either in the CS-contralateral or CS-ipsilateral hemisphere. After overnight consolidation, threat memory was attenuated in the contralateral compared to the ipsilateral group, as indicated by reduced startle eye-blink potentiation. There was no evidence for a difference between simple and complex stimuli, or that CS identification or conditioning was affected, suggesting a stronger effect of cTBS on consolidation than on initial stimulus processing. We propose that non-invasive stimulation of sensory cortex may provide a new avenue for interfering with threat memories in humans.
Fungal succession on the decomposition of three plant species from a Brazilian mangrove
Authors: Moitinho Marta A. , Chiaramonte Josiane B. , Bononi Laura , Gumiere Thiago , Melo Itamar S. , Taketani Rodrigo G.
Published: June 2021

Leaf decomposition is the primary process in release nutrients in the dynamic mangrove habitat, supporting the ecosystem food webs. On most environments, fungi are an essential part of this process. However, due to the peculiarities of mangrove forests, this group is currently neglected. Thus, this study tests the hypothesis that fungal community display an specific succession pattern in different mangrove species. A molecular approach was employed to investigate the dynamics of the fungal community during the decomposition of three common plant species (Rhizophora mangle, Laguncularia racemosa, and Avicennia schaueriana) from the mangrove habitat located at the southeast of Brazil. Plant material was the primary driver of fungi communities but time also was marginally significant for the process, and evident changes in the fungal community during the decomposition process were observed. The five most abundant classes common to all the three plant species were Saccharomycetes, Sordariomycetes, Tremellomycetes, Eurotiomycetes, and Dothideomycetes, all belonging to the Phylum Ascomycota. Microbotryomycetes class were shared only by A. schaueriana and L. racemosa, while Agaricomycetes class were shared by L. racemosa and R. mangle. The class Glomeromycetes were shared by A. schaueriana and R. mangle. The analysis of the core microbiome showed that Saccharomycetes was the most abundant class. In the variable community, Sordariomycetes was the most abundant one, mainly in the Laguncularia racemosa plant. The results presented in this work shows a specialization of the fungal community regarding plant material during mangrove litter decomposition.
Komagataeibacter tool kit (KTK): a modular cloning system for multigene constructs and programmed protein secretion from cellulose producing bacteria
Authors: Goosens Vivianne J , Walker Kenneth T , Aragon Silvia M , Singh Amritpal , Senthivel Vivek R , Dekker Linda , Caro-Astorga Joaquin , Buat Marianne L A , Song Wenzhe , Lee Koon-Yang , Ellis Tom
Published: June 2021

Bacteria proficient at producing cellulose are an attractive synthetic biology host for the emerging field of Engineered Living Materials (ELMs). Species from the Komagataeibacter genus produce high yields of pure cellulose materials in a short time with minimal resources, and pioneering work has shown that genetic engineering in these strains is possible and can be used to modify the material and its production. To accelerate synthetic biology progress in these bacteria, we introduce here the Komagataeibacter tool kit (KTK), a standardised modular cloning system based on Golden Gate DNA assembly that allows DNA parts to be combined to build complex multigene constructs expressed in bacteria from plasmids. Working in Komagataeibacter rhaeticus, we describe basic parts for this system, including promoters, fusion tags and reporter proteins, before showcasing how the assembly system enables more complex designs. Specifically, we use KTK cloning to reformat the Escherichia coli curli amyloid fibre system for functional expression in K. rhaeticus, and go on to modify it as a system for programming protein secretion from the cellulose producing bacteria. With this toolkit, we aim to accelerate modular synthetic biology in these bacteria, and enable more rapid progress in the emerging ELMs community.
Gotree/Goalign : Toolkit and Go API to facilitate the development of phylogenetic workflows
Authors: Lemoine Frédéric , Gascuel Olivier
Published: June 2021

Besides computer intensive steps, phylogenetic analysis workflows are usually composed of many small, reccuring, but important data manipulations steps. Among these, we can find file reformatting, sequence renaming, tree re-rooting, tree comparison, bootstrap support computation, etc. These are often performed by custom scripts or by several heterogeneous tools, which may be error prone, uneasy to maintain and produce results that are challenging to reproduce. For all these reasons, the development and reuse of phylogenetic workflows is often a complex task. We identified many operations that are part of most phylogenetic analyses, and implemented them in a toolkit called Gotree/Goalign. The Gotree/Goalign toolkit implements more than 120 user-friendly commands and an API dedicated to multiple sequence alignment and phylogenetic tree manipulations. It is developed in Go, which makes executables efficient, easily installable, integrable in workflow environments, and parallelizable when possible. This toolkit is freely available on most platforms (Linux, MacOS and Windows) and most architectures (amd64, i386). Sources and binaries are available on GitHub at https://github.com/evolbioinfo/gotree, Bioconda, and DockerHub.