bluuebunny/crossref_metadata_2025 huggingface dataset:
Divergent evolution of genetic sex determination mechanisms along environmental gradients
Authors: Schenkel Martijn A. , Billeter Jean-Christophe , Beukeboom Leo W. , Pen Ido
Published: May 2022

Sex determination (SD) is a crucial developmental process, but its molecular underpinnings are very diverse, both between and within species. SD mechanisms have traditionally been categorized as either genetic (GSD) or environmental (ESD), depending on the type of cue that triggers sexual differentiation. However, mixed systems, with both genetic and environmental components, are more prevalent than previously thought. Here, we show theoretically that environmental effects on expression levels of genes within SD regulatory mechanisms can easily trigger within-species evolutionary divergence of SD mechanisms. This may lead to the stable coexistence of multiple SD mechanisms and to spatial variation in the occurrence of different SD mechanisms along environmental gradients. We applied the model to the SD system of the housefly, a global species with world-wide latitudinal clines in the frequencies of different SD systems, and found that it correctly predicted these clines if specific genes in the housefly SD system were assumed to have temperature-dependent expression levels. We conclude that environmental sensitivity of gene regulatory networks may play an important role in diversification of SD mechanisms.
Influence of culturing media components on the growth and microbial induced calcium carbonate precipitation (MICP) activity of Lysinibacillus sphaericus
Authors: Rahmaninezhad Seyed Ali , Farnam Yaghoob A. , Schauer Caroline L. , Raeisi Najafi Ahmad , Sales Christopher M.
Published: May 2022

In order to identify appropriate environmental conditions and media components that are either essential or that enhance its growth and Microbial induced calcium carbonate precipitation (MICP) activity, in this study, a series of experiments were conducted to investigate the effects of media components and oxygen conditions on the growth rate and MICP activity of Lysinibacillus sphaericus strain MB 284. From these experiments, it was observed that aerobic conditions could lead to increased calcium carbonate production and up to three times faster growth rates by strain MB284 when compared to anoxic conditions. It was also determined that considering the measured growth rate, final biomass concentration, ureolysis activity, amount of calcium carbonate precipitation, and cost of media components for designing undefined culture media for industrial applications, yeast extract is the most economically appropriate option. In our attempts to grow strain MB284 in urea, sucrose, and ammonium acetate as its sole carbon source in minimal media, it was observed it is auxotrophic and that casamino acids and casein are essential for its growth. Even though our experiments agree with the literature that the addition of urea enhances the growth and MICP activity of L. sphaericus, it was discovered that when the initial urea concentration was greater than 3 g/l, the growth rate of strain MB284 can be temporarily inhibited until enough cells and urease are produced. These results reveal that the growth and MICP activity of strain MB284 during its application for bio-self healing can be highly dependent on environmental and nutrient conditions.

Importance

Aerobic conditions increase calcium carbonate production by strain MB284

yeast extract is the most economically appropriate option for industrial applications of MICP

Lysinibacillus sphaericus strain MB 284 is auxotroph and casamino acids and casein are essential for its growth

the growth rate of strain MB284 can be temporarily inhibited with urea
Systematic approach to outcome assessment from coded electronic healthcare records in the DaRe2THINK NHS-embedded randomised trial
Authors: Wang Xiaoxia , Mobley Alastair R , Tica Otilia , Okoth Kelvin , Ghosh Rebecca E , Myles Puja , Williams Tim , Haynes Sandra , Nirantharakumar Krishnarajah , Shukla David , Kotecha Dipak
Published: May 2022

Background

Improving the efficiency of clinical trials is key to their continued importance in directing evidence-based patient care. Digital innovations, in particular the use of electronic healthcare records (EHR), allow for large-scale screening and follow-up of participants. However, it is critical these developments are accompanied by robust and transparent methods that can support high quality and high clinical value research.

Methods

The DaRe2THINK trial includes a series of novel processes, including nationwide pseudonymised pre-screening of the primary care EHR across England, digital enrolment, remote e-consent, and ‘no-visit’ follow-up by linking all primary and secondary care health data with patient-reported outcomes.

Findings

DaRe2THINK is a pragmatic, healthcare-embedded randomised trial testing whether earlier use of direct oral anticoagulants in patients with prior or current atrial fibrillation can prevent thromboembolic events and cognitive decline (www.birmingham.ac.uk/dare2think). This paper outlines the systematic approach and methodology employed to define patient information and outcome events. This includes transparency on all medical code lists and phenotypes used in the trial across a variety of national data sources, including Clinical Practice Research Datalink Aurum (primary care), Hospital Episode Statistics (secondary care) and the Office for National Statistics (mortality).

Interpretation

Co-designed by a patient and public involvement team, DaRe2THINK presents an opportunity to transform the approach to randomised trials in the setting of routine healthcare, providing high-quality evidence generation in populations representative of the community at-risk.
A multivariate genetic analysis of environmental sensitivity, anxiety sensitivity and reported life events in adolescents
Authors: Peel Alicia J. , Oginni Olakunle , Assary Elham , Krebs Georgina , Lockhart Celestine , McGregor Thomas , Palaiologou Elisavet , Ronald Angelia , Danese Andrea , Eley Thalia C.
Published: May 2022

Background

Despite being considered a measure of environmental risk, reported life events are partly heritable. One mechanism that may contribute to their heritability is genetic influences on sensitivity. These sensitivity biases can relate to how individuals process the contextual aspects of their environment (environmental sensitivity) or how they interpret their own physical and emotional responses (anxiety sensitivity). The aim of this study was to explore the genetic and environmental overlap between self-reported life events and measures of sensitivity.

Methods

At age 17, individuals (N = 2,939) from the Twins Early Development Study (TEDS) completed measures of environmental sensitivity (Highly Sensitive Child Scale) and anxiety sensitivity (Children’s Anxiety Sensitivity Index), as well as reporting on their experience of 20 recent life events. Using multivariate Cholesky decomposition models, we investigated the shared genetic and environmental influences on the associations between these measures of sensitivity and the number of reported life events, as well as both negative and positive ratings of life events.

Results

The majority of the associations between anxiety sensitivity, environmental sensitivity and reported life events were explained by shared genetic influences (59%-75%), with the remainder explained by non-shared environmental influences (25%-41%). Environmental sensitivity showed comparable genetic correlations with both negative and positive ratings of life events (rA= .21 and .15), anxiety sensitivity only showed a significant genetic correlation with negative ratings of life events (rA= .33). Approximately 10% of the genetic influences on reported life events were accounted for by genetic influences shared with anxiety sensitivity and environmental sensitivity.

Conclusions

A proportion of the heritable component of reported life events is captured by measures of sensitivity. Differences in how individuals process the contextual aspects of the environment or interpret their own physical and emotional response to environmental stimuli may be one mechanism through which genetic liability influences the subjective experience of life events.
Episodic memory formation in unrestricted viewing
Authors: Nikolaev Andrey R. , Bramão Inês , Johansson Roger , Johansson Mikael
Published: May 2022

The brain systems of episodic memory and oculomotor control are tightly linked, suggesting a crucial role of eye movements in memory. But little is known about the neural mechanisms of memory formation across eye movements in unrestricted viewing behavior. Here, we leverage simultaneous eye tracking and EEG recording to examine episodic memory formation in free viewing. Participants memorized multi-element events while their EEG and eye movements were concurrently recorded. Each event comprised elements from three categories (face, object, place), with two exemplars from each category, in different locations on the screen. A subsequent associative memory test assessed participants’ memory for the between-category associations that specified each event. We used a deconvolution approach to overcome the problem of overlapping EEG responses to sequential saccades in free viewing. Brain activity was time-locked to the fixation onsets, and we examined EEG power in the theta and alpha frequency bands, the putative oscillatory correlates of episodic encoding mechanisms. Three modulations of fixation-related EEG predicted high subsequent memory performance: 1) theta increase at fixations afterbetween-categorygaze transitions, 2) theta and alpha increase at fixations afterwithin-elementgaze transitions, 3) alpha decrease at fixations afterbetween-exemplargaze transitions. Thus, event encoding with unrestricted viewing behavior was characterized by three neural mechanisms, manifested in fixation-locked theta and alpha EEG activity that rapidly turned on and off during the unfolding eye movement sequences. These three distinct neural mechanisms may be the essential building blocks that subserve the buildup of coherent episodic memories during unrestricted viewing behavior.
Design and off-target prediction for antisense oligomers targeting bacterial mRNAs with the MASON webserver
Authors: Jung Jakob , Popella Linda , Do Phuong Thao , Pfau Patrick , Vogel Jörg , Barquist Lars
Published: May 2022

Antisense oligomers (ASOs) such as peptide nucleic acids (PNAs), designed to inhibit the translation of essential bacterial genes, have emerged as attractive sequence- and species-specific programmable RNA antibiotics. Yet, potential drawbacks include unwanted side effects caused by their binding to transcripts other than the intended target. To facilitate the design of PNAs with minimal off-target effects, we developed MASON (MakeAntiSenseOligomersNow), a webserver for the design of PNAs that target bacterial mRNAs. MASON generates PNA sequences complementary to the translational start site of a bacterial gene of interest and reports critical sequence attributes and potential off-target sites. We based MASON’s off-target predictions on experiments in which we treatedSalmonella entericaserovar Typhimurium with a series of 10mer PNAs derived from a PNA targeting the essential geneacpPbut carrying two serial mismatches. Growth inhibition and RNA-sequencing (RNA-seq) data revealed that PNAs with terminal mismatches are still able to targetacpP, suggesting wider off-target effects than anticipated. Comparison of these results to an RNA-seq dataset from uropathogenicEscherichia coli(UPEC) treated with eleven different PNAs confirmed our findings are not unique toSalmonella. We believe that MASON’s off-target assessment will improve the design of specific PNAs and other ASOs.
Compound specific stable isotope analysis of amino acid nitrogen reveals detrital support of microphytobenthos in the Dutch Wadden Sea benthic food web
Authors: Riekenberg Philip M. , van der Heide Tjisse , Holthuijsen Sander J. , van der Veer Henk W. , van der Meer Marcel T.J.
Published: May 2022

The Wadden Sea is the world’s largest intertidal ecosystem and provides vital food resources for a large number of migratory bird and fish species during seasonal stopovers. Previous work using bulk stable isotope analysis of carbon found that microphytobenthos was the dominant resource use fueling the food web with particulate organic matter making up the remainder. However, this work was unable to account for the trophic structure of the food web or the considerable increase in δ15N values of bulk tissue throughout the benthic food web occurring in the Eastern regions of the Dutch Wadden Sea. Here, we combine compound specific and bulk analytical stable isotope techniques to further resolve the trophic structure and resource use throughout the benthic food web in the Wadden Sea. Analysis of δ15N for trophic and source amino acids allowed for better identification of trophic relationships due to the integration of underlying variation in the nitrogen resources supporting the food web. Baseline integrated trophic position estimates using glutamic acid (Glu) and phenylalanine (Phe) allow for disentanglement of baseline variations in underlying δ15N sources supporting the ecosystem and trophic shifts resulting from changes in ecological relationships. Through this application we further confirmed dominant ecosystem support by microphytobenthos derived resources, although to a lesser extent than previously estimated. In addition to phytoplankton derived particulate organic matter and microphytobenthos supported from nutrients from the overlying water column there appears to be an additional resource supporting the benthic community. From the stable isotope mixing models, a subset of species appears to focus on microphytobenthos supported off recycled (porewater) N and/or detrital organic matter mainly driven by increased phenylalanine δ15N values. This additional resource within microphytobenthos may play a role in subsidizing the exceptional benthic productivity observed within the Wadden Sea ecosystem and reflect division in microphytobenthos support along green (herbivory) and brown (recycled/detrital) food web pathways.
Human skeletal muscle ageing atlas
Authors: Kedlian Veronika R. , Wang Yaning , Liu Tianliang , Chen Xiaoping , Bolt Liam , Shen Zhuojian , Fasouli Eirini S. , Prigmore Elena , Kleshchevnikov Vitalii , Li Tong , Lawrence John E , Huang Ni , Guo Qin , Yang Lu , Polański Krzysztof , Dabrowska Monika , Tudor Catherine , Li Xiaobo , Bayraktar Omer , Patel Minal , Meyer Kerstin B. , Kumasaka Natsuhiko , Mahbubani Krishnaa T. , Xiang Andy Peng , Saeb-Parsy Kourosh , Teichmann Sarah A , Zhang Hongbo
Published: May 2022

Skeletal muscle ageing increases the incidence of age-associated frailty and sarcopenia in the elderly worldwide, leading to increased morbidity and mortality. However, our understanding of the cellular and molecular mechanisms of muscle ageing is still far from complete. Here, we generate a single-cell and single-nucleus transcriptomic atlas of skeletal muscle ageing from 15 donors across the adult human lifespan, accompanied by myofiber typing using imaging. Our atlas reveals ageing mechanisms acting across different compartments of the muscle, including muscle stem cells (MuSCs), myofibers and the muscle microenvironment. Firstly, we uncover two mechanisms driving MuSC ageing, namely a decrease in ribosome biogenesis and an increase in inflammation. Secondly, we identify a set of nuclei populations explaining the preferential degeneration of the fast-twitch myofibers and suggest two mechanisms acting to compensate for their loss. Importantly, we identify a neuromuscular junction accessory population, which helps myofiber to compensate for aged-related denervation. Thirdly, we reveal multiple microenvironment cell types contributing to the inflammatory milieu of ageing muscle by producing cytokines and chemokines to attract immune cells. Finally, we provide a comparable mouse muscle ageing atlas and further investigate conserved and specific ageing hallmarks across species. In summary, we present a comprehensive human skeletal muscle ageing resource by combining different data modalities, which significantly expands our understanding of muscle biology and ageing.
Sympathetic neurons secrete retrogradely transported TrkA on extracellular vesicles
Authors: Mason Ashley J , Keeler Austin B , Kabir Farah , Winckler Bettina , Deppmann Christopher
Published: May 2022

Neuronal derived extracellular vesicles (EVs) have been well described in the central nervous system; however, studies in the peripheral nervous system have largely focused on EVs derived from supporting cell types such as endothelial cells or glia. Here we isolate EVs derived from sympathetic neurons and characterize them using immunoblot assays, nanoparticle tracking analysis and cryo-electron microscopy. Sizing of sympathetic EVs reveal a predominant peak between 45-75 nm as well as a range of larger sizes (90 nm to >350 nm), possibly due to multiple biogenic origins. We identified TrkA, a receptor for nerve growth factor (NGF), as a cargo for sympathetic EVs. Furthermore, TrkA on EVs was phosphorylated, indicating activated TrkA receptor. TrkA binds NGF at the axonal tip and is endocytosed and transported to the soma in signaling endosomes. We therefore examined if TrkA originating in the axon tip was subsequently able to be packaged into EVs and secreted by the somatodendritic domain of neurons. Using a compartmentalized culture system, we found that TrkA derived from endosomes originating in the distal axon can be detected on EVs secreted from the somatodendritic domain. In addition, inhibition of classic TrkA downstream pathways, specifically in somatodendritic compartments greatly decreases TrkA packaging into EVs. Our results suggest a novel trafficking route for TrkA: it can travel long distances to the cell body, be packaged into EVs and secreted. Secretion of TrkA via EVs appears to be regulated by its own downstream effector cascades, raising intriguing future questions about novel functionalities associated with TrkApositiveEVs.
Context-dependent 3D genome regulation by cohesin and related factors
Authors: Nakato Ryuichiro , Sakata Toyonori , Wang Jiankang , Nagai Luis Augusto Eijy , Oba Gina Miku , Bando Masashige , Shirahige Katsuhiko
Published: May 2022

Cohesin plays vital roles in chromatin folding and gene expression regulation, cooperating with such factors as cohesin loaders, unloaders, acetyltransferase, and the insulation factor CTCF. Although various models of regulation have been proposed (e.g., loop extrusion), how cohesin and related factors collectively or individually regulate the hierarchical chromatin structure and gene expression remains unclear. In this study, we have depleted cohesin and related factors and then conducted a comprehensive evaluation of the resulting 3D genome, transcriptome and epigenome data. We observed substantial variation in depletion effects among factors at topologically associating domain (TAD) boundaries and on interTAD interactions, which were partly related to epigenomic status. Gene expression changes were highly correlated with direct cohesin binding and gain of TAD boundaries than with the loss of boundaries. Our results suggested that cohesin positively regulates gene expression, whereas other mechanisms (e.g., cohesin turnover and acetylation) add to the diversity of this pattern of dysregulation. Moreover, cohesin was broadly enriched in active compartment A, but not in compartment B, which were retained even after CTCF depletion. Our rich dataset and the subsequent data-driven analysis support the context-specific regulation of chromatin folding by cohesin and related factors.
Estimation of site frequency spectra from low-coverage sequencing data using stochastic EM reduces overfitting, runtime, and memory usage
Authors: Rasmussen Malthe Sebro , Garcia-Erill Genís , Korneliussen Thorfinn Sand , Wiuf Carsten , Albrechtsen Anders
Published: May 2022

The site frequency spectrum (SFS) is an important summary statistic in population genetics used for inference on demographic history and selection. However, estimation of the SFS from called genotypes introduce bias when working with low-coverage sequencing data. Methods exist for addressing this issue, but sometimes suffer from two problems. First, they can have very high computational demands, to the point that it may not be possible to run estimation for genome-scale data. Second, existing methods are prone to overfitting, especially for multi-dimensional SFS estimation. In this article, we present a stochastic expectation-maximisation algorithm for inferring the SFS from NGS data that addresses these challenges. We show that this algorithm greatly reduces runtime and enables estimation with constant, trivial RAM usage. Further, the algorithm reduces overfitting and thereby improves downstream inference. An implementation is available at github.com/malthesr/winsfs.
Perceptual similarity judgments do not predict the distribution of errors in working memory
Authors: Tomić Ivan , Bays Paul M.
Published: May 2022

Population coding models provide a quantitative account of visual working memory (VWM) retrieval errors with a plausible link to the response characteristics of sensory neurons. Recent work has provided an important new perspective linking population coding to variables of signal detection, including d-prime, and put forward a new hypothesis: that the distribution of recall errors on, e.g., a color wheel, is a consequence of the psychological similarity between points in that stimulus space, such that the exponential-like psychophysical distance scaling function can fulfil the role of population tuning and obviate the need to fit a tuning width parameter to recall data. Using four different visual feature spaces, we measured psychophysical similarity and memory errors in the same participants. Our results revealed strong evidence for a common source of variability affecting similarity judgments and recall estimates, but did not support any consistent relationship between psychophysical similarity functions and VWM errors. At the group level, the responsiveness functions obtained from the psychophysical similarity task diverged strongly from those that provided the best fit to working memory errors. At the individual level, we found convincing evidence against an association between observed and best-fitting similarity functions. Finally, our results show that the newly proposed exponential-like responsiveness function has in general no advantage over the canonical von Mises (circular normal) function assumed by previous population coding models.
Impact of bioactive molecule inclusion in lyophilized silk scaffolds varies betweenin vivoandin vitroassessments
Authors: Jameson Julie F , Pacheco Marisa O , Bender Elizabeth C , Kotta Nisha M , Black Lauren D , Kaplan David L , Grasman Jonathan M , Stoppel Whitney L
Published: May 2022

Biomaterials can influence the coordinated efforts required to achieve tissue rehabilitation. Sponge-like silk fibroin scaffolds that include bioactive molecules have been shown to influence tissue repair. However, the mechanisms by which scaffold formulations elicit desiredin vivoresponses is unclear. Here, acellular silk scaffolds consisting of type I collagen, heparin, and/or vascular endothelial growth factor (VEGF) were used to investigate material fabrication and composition parameters that drive scaffold degradation, cell infiltration, and adipose tissue depositionin vivo. In subcutaneous implants, scaffold degradation was assessed, and results show that the percentage of cells infiltrating the scaffold increased when scaffold formulations contained bioactive molecules. To gain further insight, calculatedin vitroenzymatic degradation rates increased with higher enzyme concentrations and theoretical cleavage sites. However, the addition of type I collagen and heparin to the scaffold at relevant concentrations did not change degradation rates, compared to silk alone. Thesein vitroresults are contrary to observationsin vivo, where bioactive molecules influence local protein deposition, immune cell infiltration rates, and vascularization. Thus, quantitativein vitroandin vivoevaluations aid in determining the mechanisms by which biomaterials influence tissue repair and support intentional biomaterial design for clinical applications.

Graphical Abstract

This work examines the role of scaffold fabrication and bioactive molecule inclusion on the enzymatic degradation of silk fibroin-based lyophilized sponges. Specifically, the roles of collagen I, heparin, and vascular endothelial growth factor are analyzed to determine the impact of formulation on rate of degradation. In addition, scaffolds are either pre-fabricated, where these bioactive molecules are included in the polymer solution prior to casting the scaffold or the bioactive molecules are introduced following scaffold formation through passive adsorption to the silk fibroin scaffold surface. Scaffolds are enzymatically degradedin vitro, and kinetic rate constants are calculated for the different formulations.In vivo, cellularity, adipose tissue accumulation, and scaffold area are assessed over time. Additionally, immunohistochemistry is used to visualize VEGF Receptor 2, CD 68, and α-smooth muscle actin over time.
Evolutionary trade-off and mutational bias could favor transcriptional over translational divergence within paralog pairs
Authors: Aubé Simon , Nielly-Thibault Lou , Landry Christian R.
Published: May 2022

How changes in the different steps of protein synthesis – transcription, translation and degradation – contribute to differences of protein abundance among genes is not fully understood. There is however accumulating evidence that transcriptional divergence might have a prominent role. Here, we show that yeast paralogous genes are more divergent in transcription than in translation. We explore two causal mechanisms for this predominance of transcriptional divergence: an evolutionary trade-off between the precision and economy of gene expression and a larger mutational target size for transcription. Performing simulations within a minimal model of post-duplication evolution, we find that both mechanisms are consistent with the observed divergence patterns. We also investigate how additional properties of the effects of mutations on gene expression, such as their asymmetry and correlation across levels of regulation, can shape the evolution of duplicates. Our results highlight the importance of fully characterizing the distributions of mutational effects on transcription and translation. They also show how general trade-offs in cellular processes and mutation bias can have far-reaching evolutionary impacts.
The Balance between Saturated and Unsaturated Fatty Acids Regulates Ovarian Cancer Cell Fate
Authors: Zhao Guangyuan , Tan Yuying , Cardenas Horacio , Vayngart David , Huang Hao , Wang Yinu , Keathley Russell , Wei Jian-Jun , Ferreira Christina R. , Cheng Ji-Xin , Matei Daniela
Published: May 2022

Fatty acids are an important source of energy and a key component of phospholipids in membranes and organelles. Saturated (SFAs) are converted into unsaturated fatty acids (UFAs) by stearoyl Co-A desaturase (SCD), an enzyme highly active in cancer. Here we studied how the balance between SFAs and UFAs maintained by SCD impacts cancer cell survival and tumor progression. SCD depletion or inhibition caused lower levels of UFAs vs. SFAs and altered fatty acyl chain plasticity, as demonstrated by lipidomics and stimulated Raman spectroscopy (SRS). Further, the loss of equilibrium between UFAs and SFAs resulting from SCD knock down triggered endoplasmic reticulum (ER) stress response with brisk activation of IRE1α/XBP1 and PERK/eIF2α/ATF4 axes. Stiff and disorganized ER membrane was visualized by electron microscopy and SRS imaging in cells in which SCD was knocked down. The induction of long-term mild ER stress or short-time severe ER stress by the increased levels of SFAs and loss of UFAs led to cell death. However, ER stress and apoptosis could be readily rescued by supplementation with UFAs and re-equilibration of SFA/UFA levels. The effects of SCD knockdown or inhibition observed in vitro, translated into suppression of intraperitoneal tumor growth in xenograft models. Furthermore, a combined intervention using an SCD inhibitor and an SFA enriched diet, initiated ER stress in tumors growing in vivo and potently blocked their dissemination. In all, our data support SCD as a key regulator of the cancer cell fate under metabolic stress and point to new treatment strategies targeting the lipid balance.

Significance Statement

We show that the balance between saturated and unsaturated fatty acids tightly regulated by the desaturase SCD impacts the survival of cancer cells; increased levels of unsaturation being protective against ER stress induced apoptosis. Decreasing fatty acid unsaturation, either through SCD depletion or through SCD inhibition coupled with a dietary intervention blocks tumor progression in vivo. Our findings support the concept of targeting the lipid balance as a new target in cancer.
Reward expectations direct learning and drive operant matching inDrosophila
Authors: Rajagopalan Adithya E. , Darshan Ran , Hibbard Karen L. , Fitzgerald James E. , Turner Glenn C.
Published: May 2022

Foraging animals must use decision-making strategies that dynamically adapt to the changing availability of rewards in the environment. A wide diversity of animals do this by distributing their choices in proportion to the rewards received from each option, Herrnstein’s operant matching law. Theoretical work suggests an elegant mechanistic explanation for this ubiquitous behavior, as operant matching follows automatically from simple synaptic plasticity rules acting within behaviorally relevant neural circuits. However, no past work has mapped operant matching onto plasticity mechanisms in the brain, leaving the biological relevance of the theory unclear. Here we discovered operant matching inDrosophilaand showed that it requires synaptic plasticity that acts in the mushroom body and incorporates the expectation of reward. We began by developing a novel behavioral paradigm to measure choices from individual flies as they learn to associate odor cues with probabilistic rewards. We then built a model of the fly mushroom body to explain each fly’s sequential choice behavior using a family of biologically-realistic synaptic plasticity rules. As predicted by past theoretical work, we found that synaptic plasticity rules could explain fly matching behavior by incorporating stimulus expectations, reward expectations, or both. However, by optogenetically bypassing the representation of reward expectation, we abolished matching behavior and showed that the plasticity rule must specifically incorporate reward expectations. Altogether, these results reveal the first synaptic level mechanisms of operant matching and provide compelling evidence for the role of reward expectation signals in the fly brain.
Common facultative endosymbionts do not influence sensitivity of cereal aphids to pyrethroids
Authors: Leybourne D J , Melloh P , Martin E A
Published: May 2022

Cereal aphids, including the bird cherry-oat aphid, Rhopalosiphum padi, and the grain aphid, Sitobion avenae, can transmit viruses that significantly reduce crop yields. To mitigate against yield losses, insecticides are routinely used to manage aphid populations.

Aphids can form relationships with endosymbionts that confer fitness benefits or consequences to the aphid. Recent artificial inoculation experiments indicate that endosymbionts could increase aphid susceptibility to insecticides, but this has not been explored using aphid populations naturally infected with endosymbionts.

Here, we sampled aphids from an important cereal production region in Lower Saxony, Germany. We characterised the endosymbiont profile of these aphid populations and conducted pyrethroid dose-response assays to test the hypothesis that facultative endosymbionts increase aphid susceptibility to insecticides.

We find that the level of insecticide susceptibility is highly variable in S. avenae and we identify populations that are sensitive and tolerant to pyrethroids, including populations collected from the same field. For R. padi, we find evidence for decreased sensitivity to pyrethroids, representing the first report of reduced sensitivity to pyrethroids in R. padi sampled from Central Europe.

We detected high endosymbiont infection frequencies in the aphid populations. 84% of aphids carry one facultative endosymbiont and 9% of aphids carry two facultative endosymbionts. We detected associations with Regiella insecticola, Fukatsia symbiotica, and Hamiltonella defensa. However, we do not identify a link between endosymbiont infection and insecticide susceptibility, indicating that other factors may govern the development of insecticide resistance and the need for alternative management strategies.
Nitric oxide is not responsible for the initial sensory-induced neurovascular coupling response in mouse cortex
Authors: Lee L , Boorman L , Glendenning E , Shen C , Berwick J , Howarth C
Published: May 2022

Neurovascular coupling ensures that changes in neural activity are accompanied by localised changes in cerebral blood flow. While much is known about the involvement of excitatory neurons in neurovascular coupling, the role of inhibitory interneurons is unresolved. While nNOS-expressing interneurons have been shown to be capable of eliciting vasodilation, the role of nitric oxide in functional hyperemia remains a matter of debate. Therefore in the present study we applied a combination of optogenetic and pharmacological approaches, 2-dimensional optical imaging spectroscopy, and electrophysiology to investigate the role of nitric oxide in neurovascular coupling responses evoked by nNOS-expressing interneurons and whisker stimulation in mouse sensory cortex. The haemodynamic response evoked by nNOS-expressing interneurons was significantly altered in the presence of the NOS inhibitor LNAME, revealing a large initial 20-HETE-dependent vasoconstriction. In contrast, the haemodynamic response induced by sensory stimulation was largely unchanged by LNAME. Our results suggest that while nitric oxide plays a key role in neurovascular responses evoked by nNOS-expressing interneurons it does not mediate the initial sensory-induced neurovascular coupling response in mouse cortex. Thus, our results call into question the involvement of nNOS-expressing interneurons and nitric oxide in sensory-evoked functional hyperemia.
STX5’s flexibility in SNARE pairing supports Golgi functions
Authors: D’Souza Zinia , Pokrovskaya Irina , Lupashin Vladimir V.
Published: May 2022

The intracellular transport system is an evolutionally conserved, essential, and highly regulated network of organelles and transport vesicles that traffic protein and lipid cargoes within the cell. The events of vesicle formation, budding and fusion are orchestrated by the trafficking machinery – an elaborate set of proteins including small GTPases, vesicular coats, tethers, and SNAREs. The Golgi - the central organelle in this transport network, receives, modifies and sorts secretory and endocytic cargo. Glycosylation is one of the major modifications that occur within the Golgi, which houses enzymes and other components of glycosylation machinery. According to the current Golgi maturation model, Golgi resident proteins are constantly recycled from the late (trans) Golgi compartments to the early compartment (cis) by the evolutionary conserved vesicular trafficking machinery. The key modulator of vesicular trafficking and glycosylation at the Golgi is the Conserved Oligomeric Golgi (COG) complex – its interaction vesicular trafficking machinery particularly Golgi SNAREs (STX5, GS28 (GOSR1), GS15 (BET1L) and YKT6) that drive fusion of incoming vesicles. Since the COG complex functions upstream of SNARE-mediated vesicle fusion, we hypothesize that depletion of Golgi v-SNAREs would mirror defects observed in COG deficient cells. To test this, we created single and double knockouts (KO) of GS28 and GS15 in HEK293T cells and analyzed resulting mutants using a comprehensive set of biochemical, mass-spectrometry (MS) and microscopy approaches. Deletion of GS28 significantly affected GS15, but not the other two partners, STX5 and YKT6. Surprisingly, our analysis revealed that COG dysfunction is more deleterious for Golgi function than disrupting the canonical Golgi SNARE complex. Quantitative MS analysis of STX5-interacting SNAREs revealed unexpected flexibility of Golgi SNARE pairing in mammalian cells. We uncovered two novel non-canonical Golgi SNARE complexes – STX5/VTI1B/GS15/YKT6 and STX5/SNAP29/VAMP7 which were upregulated in GS28 KO cells. Analysis of cells co-depleted for GS28/SNAP29 or GS28/VTI1B SNAREs revealed escalated defects in Golgi glycosylation, indicating that upregulation of these complexes functionally substitutes deleted GS28. Our data points to the remarkable plasticity in the intra-Golgi membrane fusion machinery which is controlled by the COG complex.
A very long chain fatty acid responsive transcription factor, MYB93, regulates lateral root development in Arabidopsis
Authors: Uemura Yuta , Kimura Saori , Ohta Tomomichi , Suzuki Takamasa , Mase Kosuke , Kato Hiroyuki , Sakaoka Satomi , Komine Yuki , Hotta Kazuhiro , Shimizu Motoyuki , Morikami Atsushi , Tsukagoshi Hironaka
Published: May 2022

Lateral roots (LRs) are critical to rhizosphere development in plants. Although the molecular mechanisms by which auxin regulates LR development has been studied extensively, many additional regulatory systems are thought to be involved. Based on the expression analysis of LTPG1 and 2, we found that they were specifically expressed at the developing LR primordium (LRP), and the number of LRs were reduced in these mutants. Because LTPG is a protein that transports Very Long Chain Fatty Acids (VLCFAs), we hypothesized that VLCFAs regulated LR development. We revealed that late LRP development was stunted when VLCFA levels were reduced in the synthetic mutant, kcs1-5. In this study, we established a method to analyze the LRP development stages with high temporal resolution using a deep neural network. We identified a VLCFA responsible transcription factor, MYB93, from transcriptome analysis of kcs1-5. Interestingly, MYB93 showed a carbon chain length-specific expression response after treatment of VLCFA. Furthermore, myb93 transcriptome analysis suggested that MYB93 regulated the expression of cell wall organization genes. Our results indicated that VLCFA is a regulator of LRP development through transcription factor-mediated regulation of gene expression.
Structure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies
Authors: Ko Kuang-Ting , Lennartz Frank , Mekhaiel David , Guloglu Bora , Marini Arianna , Deuker Danielle J. , Long Carole A. , Jore Matthijs M. , Miura Kazutoyo , Biswas Sumi , Higgins Matthew K.
Published: May 2022

An effective malaria vaccine remains a global health priority and vaccine immunogens which prevent transmission of the parasite will have important roles in multi-component vaccines. One of the most promising candidates for inclusion in a transmission-blocking malaria vaccine is the gamete surface protein Pfs48/45, which is essential for development of the parasite in the mosquito midgut. Indeed, antibodies which bind Pfs48/45 can prevent transmission if ingested with the parasite as part of the mosquito bloodmeal. Here we present the first structure of full-length Pfs48/45, revealing its three domains to form a dynamic, planar, triangular arrangement. From this, we show where transmission-blocking and non-blocking antibodies bind on Pfs48/45. Finally, we demonstrate that antibodies which bind across this molecule can be transmission-blocking. These studies will guide the development of future Pfs48/45-based vaccine immunogens.
Parent-of-origin detection and chromosome-scale haplotyping using long-read DNA methylation sequencing and Strand-seq
Authors: Akbari Vahid , Hanlon Vincent C. T. , O’Neill Kieran , Lefebvre Louis , Schrader Kasmintan A. , Lansdorp Peter M. , Jones Steven J.M.
Published: May 2022

Hundreds of loci in human genomes have alleles that are methylated differentially according to their parent of origin. These imprinted loci generally show little variation across tissues, individuals, and populations. We show that such loci can be used to distinguish the maternal and paternal homologs for all autosomes, without the need for the parental DNA. We integrate methylation-detecting nanopore sequencing with the long-range phase information in Strand-seq data to determine the parent of origin of chromosome-length haplotypes for both DNA sequence and DNA methylation in five trios with diverse genetic backgrounds. The parent of origin was correctly inferred for all autosomes with an average mismatch error rate of 0.31% for SNVs and 1.89% for indels. Because our method can determine whether an inherited disease allele originated from the mother or the father, we predict that it will improve the diagnosis and management of many genetic diseases.
Lineage-Specific Differences and Regulatory Networks Governing Human Chondrocyte Development
Authors: Richard Daniel , Pregizer Steven , Venkatasubramanian Divya , Muthuirulan Pushpanathan , Liu Zun , Capellini Terence D. , Craft April M.
Published: May 2022

To address large gaps in our understanding of the molecular regulation of articular and growth plate cartilage development in humans, we used our directed differentiation approach to generate these distinct cartilage tissues from human embryonic stem cells. The resulting transcriptomic profiles of hESC-derived articular and growth plate chondrocytes were similar to fetal epiphyseal and growth plate chondrocytes, with respect to genes both known and previously unknown to cartilage biology. With the goal to characterize the regulatory landscapes accompanying these respective transcriptomes, we mapped chromatin accessibility in hESC-derived chondrocyte lineages, and mouse embryonic chondrocytes, using ATAC-sequencing. Integration of the expression dataset with the differentially accessible genomic regions revealed lineage-specific gene regulatory networks. We validated functional interactions of two transcription factors (RUNX2 in growth plate chondrocytes and RELA in articular chondrocytes) with their predicted genomic targets. The maps we provide thus represent a framework for probing regulatory interactions governing chondrocyte differentiation. This work constitutes a substantial step towards comprehensive and comparative molecular characterizations of distinct chondrogenic lineages, and sheds new light on human cartilage development and biology.
Individual and organizational identity economics: the case of sustainability
Authors: Lamprinakis Lampros
Published: May 2022

Purpose

The purpose of this article is to introduce identity economics in the individual and organizational level, and highlight its impact on organizational performance, especially when dealing with foundational issues such as sustainability.

Design/methodology/approach

Identity, sustainability, and the role of personal values in organizational performance are well researched topics that have been typically addressed on different literature streams. The article draws from this diverse literature to introduce identity effects in individual and organizational levels, and further explore how such elements link to the rising popularity of the sustainability discourse and how they can affect operations in an organization.

Findings

The article highlights the importance of identity effects on organizational operations and performance, especially when dealing with foundational issues such as sustainability perceptions.

Originality/value

The article builds upon the recent developments in the field of identity economics to introduce identity in the sustainability discourse and explore how (mis)alignment between identity values on sustainability and organizational culture can affect organizational operations and individual performance.
Influence of Saudi Vision 2030 on housing-related macroeconomic variables
Authors: Hariri Mohammad
Published: May 2022

Purpose

This study aims to explore the effect of Saudi Vision 2030 and its government initiatives on macroeconomic variables related to housing.

Design/methodology/approach

This exploratory study used an empirical–analytical approach. Based on secondary data, a set of hypotheses was contrasted to verify whether there has been any change in the trends of macroeconomic variables related to housing after Saudi Vision 2030 entered into force.

Findings

The results show that the trend of percentage of housing ownership went from a continuous decrease to accelerated growth since the implementation of Saudi Vision 2030. However, the effect of these advances is not observed in non-oil gross domestic product (GDP) or in the economic activities of the construction, real estate and financial services sectors.

Research limitations/implications

This study notes that despite successful housing outcomes, it appears that Saudi Vision 2030 does not have a positive impact on non-oil GDP. Consequently, government entities should review the degree to which other economic activities contribute to non-oil GDP. A limitation of the study was that the GDP of housing construction and marketing and that of granting mortgage loans were not specifically available, nor were data on public and private investment made for implementing government initiatives.

Originality/value

To the best of the authors’ knowledge, this is the first study to explore the effect of Saudi Vision 2030 on housing and its contribution to the economy.
Embracing mobile shopping: what matters most in the midst of a pandemic?
Authors: Loh Xiu Ming , Lee Voon Hsien , Tan Garry Wei-Han , Ooi Keng-Boon , Fosso Wamba Samuel
Published: May 2022

Purpose

The COVID-19 pandemic has brought about significant changes to the lives of many people. One of which is the accelerated digitalization in the commerce sector. Hence, this study looks to determine the antecedents that affect users' mobile shopping actual use during a pandemic.

Design/methodology/approach

The research model was founded on the integration of the Protection Motivation Theory and Transactional Theory of Stress. This is in addition to further extending the integrated research model with other constructs to develop a multi-dimensional framework that accounted for the health, personal, technological and social dimensions. The data was collected from users of mobile shopping through an online survey which was then analyzed via Partial Least Squares–Structural Equation Modeling.

Findings

This study provides empirical support to establish the major role of COVID-19 pandemic in affecting the actual usage of mobile shopping. Furthermore, the determinants of actual usage of mobile shopping were found to be multi-dimensional. In particular, the Importance-Performance Map Analysis revealed that emphasis should be place on perceived vulnerability.

Originality/value

As other studies focused on users' intentions, this study looked into the factors that influence the actual usage of mobile shopping. Furthermore, this study emphasizes on the contextualization of time and situation in addition to a multi-dimensional approach toward the subject matter. Overall, this study offers practical insights to stakeholders to better tailor their mobile shopping services in times of a pandemic and advances the literature on actual usage of mobile shopping.