bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering compromised speech-in-noise intelligibility in older listeners: the role of cochlear synaptopathy
Authors: Garrett Markus , Vasilkov Viacheslav , Mauermann Manfred , Devolder Pauline , Wilson John L. , Gonzales Leslie , Henry Kenneth S. , Verhulst Sarah
Published: June 2020

Speech intelligibility declines with age and sensorineural hearing damage (SNHL). However, it remains unclear whether cochlear synaptopathy (CS), a recently discovered form of SNHL, significantly contributes to this issue. CS refers to damaged auditory-nerve synapses that innervate the inner hair cells and there is currently no go-to diagnostic test available. Furthermore, age-related hearing damage can comprise various aspects (e.g., hair cell damage, CS) that each can play a role in impaired sound perception. To explore the link between cochlear damage and speech intelligibility deficits, this study examines the role of CS for word recognition among older listeners. We first validated an envelope-following response (EFR) marker for CS using a Budgerigar model. We then applied this marker in human experiments, while restricting the speech material’s frequency content to ensure that both the EFR and the behavioral tasks engaged similar cochlear frequency regions. Following this approach, we identified the relative contribution of hearing sensitivity and CS to speech intelligibility in two age-matched (65-year-old) groups with clinically normal (n=15, 8 females) or impaired audio-grams (n=13, 8 females). Compared to a young normal-hearing control group (n = 13, 7 females), the older groups demonstrated lower EFR responses and impaired speech reception thresholds. We conclude that age-related CS reduces supra-threshold temporal envelope coding with subsequent speech coding deficits in noise that cannot be explained based on hearing sensitivity alone.

Significance Statement

Temporal bone histology reveals that cochlear synaptopathy (CS), characterized by damage to inner hair cell auditory nerve fiber synapses, precedes sensory cell damage and hearing sensitivity decline. Despite this, clinical practice primarily evaluates hearing status based on audiometric thresholds, potentially overlooking a prevalent aspect of sensorineural hearing damage due to aging, noise exposure, or ototoxic drugs—all of which can lead to CS. To address this gap, we employ a novel and sensitive EEG-based marker of CS to investigate its relationship with speech intelligibility. This study addresses a crucial unresolved issue in hearing science: whether CS significantly contributes to degraded speech intelligibility as individuals age. Our study-outcomes are pivotal for identifying the appropriate target for treatments aimed at improving impaired speech perception.
Histone deacetylase inhibition by gut microbe-generated short chain fatty acids entrains intestinal epithelial circadian rhythms
Authors: Luzader Deborah H. , Fawad Jibraan A. , Moutinho Thomas J. , Mitchell Paul G. , Brown-Steinke Kathleen , Zhao Jesse Y. , Rosselot Andrew E. , McKinney Craig A. , Hong Christian I. , Chou C. James , Papin Jason A. , Moore Sean R.
Published: June 2020

Background and aims

The circadian clock orchestrates ~24-hour oscillations of gastrointestinal (GI) epithelial structure and function that drive diurnal rhythms in the composition, localization, and metabolism of gut microbiota. Here, we use experimental and computational approaches in enteroids to reveal reciprocal effects of microbial metabolites on intestinal epithelial timekeeping by an epigenetic mechanism.

Methods

We cultured 3D PER2∷LUCIFERASE andBmal1-ELuciferasejejunal enteroids in media supplemented with sterile supernatants from the altered Schaedler Flora (ASF), a defined murine microbiota. Circadian oscillations of bioluminescent PER2 andBmal1were measured in enteroids cultured in the presence or absence of individual ASF supernatants. Separately, we applied machine learning to ASF metabolic profiles to identify phase-shifting metabolites.

Results

Filtrates from 3 of 7 ASF species (ASF360Lactobacillus intestinalis, ASF361Ligilactobacillus murinus, ASF502Clostridiumspp.) induced minimal alterations in circadian rhythms, whereas 4 ASF species (ASF356Clostridiumspp., ASF492Eubacterium plexicaudatum, ASF500Pseudoflavonifactorspp., ASF519Parabacteroides goldsteinii) induced profound, concentration-dependent phase delays. Random forest classification identified short chain fatty acids (SCFA: butyrate, propionate, acetate, and isovalerate) production as a discriminating feature of “shifters”, i.e., ASF taxa whose metabolites induce phase delay. Experiments with SCFAs confirmed machine learning predictions, with a median phase delay of 6.2 hours. Pharmacological or botanical HDAC inhibitors generated similar phase delays. Further, mithramycin A, an inhibitor of HDAC inhibition, abrogated SCFA-induced phase delays by 20% (P<0.05). Key findings were reproducible in humanBmal1-luciferaseenteroids.

Conclusions

Gut microbe-generated SCFAs entrain intestinal epithelial circadian rhythms, in part, by an HDACi-dependent mechanism, with critical implications for understanding microbial and circadian network regulation of intestinal epithelial homeostasis.
Idiosyncratic Perception: A Link Between Acuity, Perceived Position, and Apparent Size
Authors: Wang Zixuan , Murai Yuki , Whitney David
Published: June 2020

Perceiving the positions of objects is a prerequisite for most other visual and visuomotor functions, but human perception of object position varies from one individual to the next. The source of these individual differences in perceived position and their perceptual consequences are unknown. Here, we tested whether idiosyncratic biases in the underlying representation of visual space propagate across different levels of visual processing. In Experiment 1, using a position matching task, we found stable, observer-specific compressions and expansions within local regions throughout the visual field. We then measured Vernier acuity (Experiment 2) and perceived size of objects (Experiment 3) across the visual field and found that individualized spatial distortions were closely associated with variations in both visual acuity and apparent object size. Our results reveal idiosyncratic biases in perceived position and size, originating from a heterogeneous spatial resolution that carries across the visual hierarchy.
Mendelian randomization identifies folliculin expression as a mediator of diabetic retinopathy
Authors: Skol Andrew D. , Jung Segun C. , Sokovic Ana Marija , Chen Siquan , Fazal Sarah , Sosina Olukayode , Borkar Poulami , Lin Amy , Sverdlov Maria , Cao Dingcai , Swaroop Anand , Bebu Ionut ,   DCCT/ EDIC Study group, Stranger Barbara E. , Grassi Michael A.
Published: June 2020

The goal of the study was to identify genes whose aberrant expression can contribute to diabetic retinopathy. We determined differential gene expression in response to high glucose in lymphoblastoid cell lines derived from matched individuals with type 1 diabetes (T1D) with and without retinopathy. Those genes exhibiting the largest difference in glucose response between individuals with diabetes with and without retinopathy were assessed for association to diabetic retinopathy utilizing genotype data from a genome-wide association study meta-analysis. All genetic variants associated with gene expression (expression Quantitative Trait Loci, eQTLs) of the glucose response genes were tested for association with diabetic retinopathy. We detected an enrichment of the eQTLs from the glucose response genes among small association p-values and identified folliculin (FLCN) as a susceptibility gene for diabetic retinopathy. We show that expression ofFLCNin response to glucose was greater in individuals with diabetic retinopathy compared to individuals with diabetes without retinopathy. Three large, independent cohorts of individuals with diabetes revealed an association ofFLCNeQTLs to diabetic retinopathy. Mendelian randomization further confirmed a direct positive effect of increasedFLCNexpression on retinopathy in individuals with diabetes. Together, our studies integrating genetic association and gene expression implicateFLCNas a disease gene for diabetic retinopathy.
Development of genetic tools for the thermophilic filamentous fungus Thermoascus aurantiacus
Authors: Gabriel Raphael , Prinz Julia , Jecmenica Marina , Romero-Vazquez Carlos , Chou Pallas , Harth Simon , Floerl Lena , Curran Laure , Oostlander Anne , Matz Linda , Fritsche Susanne , Gorman Jennifer , Schuerg Timo , Fleißner André , Singer Steven W.
Published: June 2020

Background

Fungal enzymes are vital for industrial biotechnology, including the conversion of plant biomass to biofuels and bio-based chemicals. In recent years, there is increasing interest in using enzymes from thermophilic fungi, which often have higher reaction rates and thermal tolerance compared to currently used fungal enzymes. The thermophilic filamentous fungus Thermoascus aurantiacus produces large amounts of highly thermostable plant cell wall degrading enzymes. However, no genetic tools have yet been developed for this fungus, which prevents strain engineering efforts. The goal of this study was to develop strain engineering tools such as a transformation system, a CRISPR/Cas9 gene editing system and a sexual crossing protocol to improve enzyme production.

Results

Here we report Agrobacterium tumefaciens-mediated transformation (ATMT) of T. aurantiacus using the hph marker gene, conferring resistance to hygromycin B. The newly developed transformation protocol was optimized and used to integrate an expression cassette of the transcriptional xylanase regulator xlnR, which led to up to 500% increased xylanase activity. Furthermore, a CRISPR/Cas9 gene editing system was established in this fungus, and two different gRNAs were tested to delete the pyrG orthologue with 10% and 35% deletion efficiency, respectively. Lastly, a sexual crossing protocol was established using a hygromycin B- and a 5-fluororotic acid-resistant parent strain. Crossing and isolation of progeny on selective media was completed in a week.

Conclusion

The genetic tools developed for T. aurantiacus can now be used individually or in combination to further improve thermostable enzyme production by this fungus.
Signalome-wide assessment of erythrocyte response toPlasmodiumreveals novel targets for host-directed antimalarial intervention
Authors: Adderley Jack D. , von Freyend Simona John , Jackson Sarah A. , Bird Megan J. , Burns Amy L. , Anar Burcu , Metcalf Tom , Semblat Jean-Philippe , Billker Oliver , Wilson Danny W. , Doerig Christian
Published: June 2020

Intracellular pathogens are known to mobilise host signaling pathways to manipulate gene expression in their host cell to promote their own survival. Surprisingly, evidence is emerging that specific signal transduction elements are activated in a-nucleated erythrocytes in response to infection with malaria parasites, but the extent of this phenomenon remains unknown. Here, we fill this knowledge gap by providing a comprehensive and dynamic assessment of host erythrocyte signaling during the course of infection withPlasmodium falciparum. We used an antibody microarray that comprises 878 antibodies directed against human signaling proteins, >600 of which are phospho-specific, to interrogate the status of host erythrocyte signaling pathways at three stages of parasite development during the asexual cycle. This confirmed the pre-existing fragmentary data on the activation of a PAK-MEK pathway, and revealed the modulation of a large number of additional signaling elements during infection.

We focussed on the receptor tyrosine kinase c-MET, also known as the hepatocyte growth factor receptor, and the MAP kinase pathway component B-Raf that is reported to lie downstream of c-MET in a number of cell types. Array data validated by Western blotting revealed that activation sites of c-MET are phosphorylated in trophozoite-infected erythrocytes, and we show that treatment of parasite cultures with c-MET or B-Raf selective inhibitors have nanomolar potency againstin vitroproliferation ofP. falciparumand the phylogenetically distant speciesP. knowlesi. Furthermore, we demonstrate that a c-MET inhibitor impairsin vivoproliferation of the rodent malaria parasiteP. bergheiin mice.

Overall, we provide a comprehensive dataset on the modulation of host erythrocyte signaling during infection with malaria parasites, as well as a proof of concept that human signaling kinases identified as activated by malaria infection represent attractive targets for antimalarial intervention.
Zinc deficiency decreases bone mineral density of rat by calmodulin-induced change in calcium metabolism
Authors: Yu Qingli , Zhao Jiali , Chen Yanfeng , Li Zixiang , Sun Yongzhi , Fan Lina , Wang Maoqing , Peng Chenghai
Published: June 2020

(1)

Background

Zinc deficiency decreases bone mineral density (BMD), but it is not known whether decreased BMD is a result of altered calcium absorption, excretion, and/or tissue distribution. To identified the associations between zinc deficiency, calcium metabolism and decreased BMD.

(2)

Methods

we performed two zinc deficiency experiments. In the first experiment, male rats (5-week-old) were fed a low zinc diet for four weeks. We measured serum zinc, alkaline phosphatase, Ca2+, osteocalcin, calcitonin, parathyroid hormone (PTH), calcium concentrations in feces and urine, BMD, and femur bone length and weight. In the second experiment, male rats (3-week-old) were fed a low zinc diet for five weeks. In addition to the aforesaid indicators, we measured the concentrations of zinc, total calcium, and calmodulin in multiple tissues.

(3)

Results

In both experiments, serum zinc, alkaline phosphatase, fecal and urine calcium, BMD, and bone weight of the low zinc diet group (LZG) were reduced compared with the normal zinc diet group (NZG)and pair-fed group (PZG); PTH increased significantly. Serum Ca2+, osteocalcin, and calcitonin concentrations were unchanged and not associated with decreased BMD. In the second experiment, zinc concentrations were reduced in serum, skeletal muscle, feces, and urine of LZG animals compared with NZG and PZG. Calmodulin in serum and skeletal muscle of the LZG group was decreased. Zinc deficiency increased total calcium concentrations in serum and skeletal muscle by promoting a decrease in calmodulin. To maintain blood Ca2+ balance, elevated PTH increased calcium reabsorption, reduced calcium excretion, stimulated bone resorption, mobilized bone calcium, and decreased BMD. (4) Conclusions: Decreased calmodulin and increased PTH induced by zinc deficiency altered calcium tissue distribution and decreased BMD of rat.
Bayesian investigation of SARS-CoV-2-related mortality in France
Authors: Duchemin Louis , Veber Philippe , Boussau Bastien
Published: June 2020

The SARS-CoV-2 epidemic in France has focused a lot of attention as it has had one of the largest death tolls in Europe. It provides an opportunity to examine the effect of the lockdown and of other events on the dynamics of the epidemic. In particular, it has been suggested that municipal elections held just before lockdown was ordered may have helped spread the virus. In this manuscript we use Bayesian models of the number of deaths through time to study the epidemic in 13 regions of France. We found that the models accurately predict the number of deaths 2 to 3 weeks in advance, and recover estimates that are in agreement with recent models that rely on a different structure and different input data. In particular, the lockdown reduced the viral reproduction number by ≈ 80%. However, using a mixture model, we found that the lockdown had had different effectiveness depending on the region, and that it had been slightly more effective in decreasing the reproduction number in denser regions. The mixture model predicts that 2.08 (95% CI: 1.85-2.47) million people had been infected by May 11, and that there were 2567 (95% CI: 1781-5182) new infections on May 10. We found no evidence that the reproduction numbers differ between week-ends and week days, and no evidence that the reproduction numbers increased on the election day. Finally, we evaluated counterfactual scenarios showing that ordering the lockdown 1 to 7 days sooner would have resulted in 19% to 76% fewer deaths, but that ordering it 1 to 7 days later would have resulted in 21% to 266% more deaths. Overall, the predictions of the model indicate that holding the elections on March 15 did not have a detectable impact on the total number of deaths, unless it motivated a delay in imposing the lockdown.
AP-2γ is Required for Maintenance of Pluripotent Mammary Stem Cells
Authors: Gu Vivian W. , Cho Edward , Thompson Dakota T. , Cassady Victoria C. , Borcherding Nicholas , Koch Kelsey E. , Wu Vincent T. , Lorenzen Allison W. , Kulak Mikhail V. , Williams Trevor , Zhang Weizhou , Weigel Ronald J.
Published: June 2020

Mammary gland ductal morphogenesis depends on the differentiation of mammary stem cells (MaSCs) into basal and luminal lineages. The AP-2γ transcription factor, encoded byTfap2c, has a central role in mammary gland development but its effect in mammary lineages and specifically MaSCs is largely unknown. Herein, we utilized an inducible, conditional knockout ofTfap2cto elucidate the role of AP-2γ in maintenance and differentiation of MaSCs. Loss of AP-2γ in the basal epithelium profoundly altered the transcriptomes and decreased the number of cells within several clusters of mammary epithelial cells, including adult MaSCs and luminal progenitors.

AP-2γ regulated the expression of genes known to be required for mammary development includingC/EBPβ, IκBα, andRspo1. As a result, AP-2γ-deficient mice exhibited repressed mammary gland ductal outgrowth and inhibition of regenerative capacity. The findings demonstrate that AP-2γ is required for maintenance of pluripotent MaSCs and their ability to develop mammary gland structures.

Highlights

AP-2γ-deficient mice exhibited repressed ductal outgrowth and regenerative capacity

Loss of AP-2γ reduced the number of mammary stem and luminal progenitor cells

AP-2γ target genes, includingC/EBPβ, IκBα, andRspo1, regulate mammary development

AP-2γ is required for maintenance of pluripotent mammary stem cells

eTOC blurb

Gu, Cho and colleagues utilized a conditional knockout ofTfap2cto examine transcriptional effects of AP-2γ on mammary stem cells. Single cell analysis demonstrated that AP-2γ-deficient mice have decreased numbers of mammary stem cells and alteration of genes required for mammary development includingC/EBPβ, IκBα, andRspo1. They demonstrate that AP-2γ is necessary for maintenance of pluripotent mammary stem cells.
Synaptic accumulation of FUS triggers age-dependent misregulation of inhibitory synapses in ALS-FUS mice
Authors: Sahadevan Sonu , Hembach Katharina M. , Tantardini Elena , Pérez-Berlanga Manuela , Hruska-Plochan Marian , Weber Julien , Schwarz Petra , Dupuis Luc , Robinson Mark D. , De Rossi Pierre , Polymenidou Magdalini
Published: June 2020

FUS is a primarily nuclear RNA-binding protein with important roles in RNA processing and transport. FUS mutations disrupting its nuclear localization characterize a subset of amyotrophic lateral sclerosis (ALS-FUS) patients, through an unidentified pathological mechanism. FUS regulates nuclear RNAs, but its role at the synapse is poorly understood. Here, we used super-resolution imaging to determine the physiological localization of extranuclear, neuronal FUS and found it predominantly near the vesicle reserve pool of presynaptic sites. Using CLIP-seq on synaptoneurosome preparations, we identified synaptic RNA targets of FUS that are associated with synapse organization and plasticity. Synaptic FUS was significantly increased in a knock-in mouse model of ALS-FUS, at presymptomatic stages, accompanied by alterations in density and size of GABAergic synapses. RNA-seq of synaptoneurosomes highlighted age-dependent dysregulation of glutamatergic and GABAergic synapses. Our study indicates that FUS accumulation at the synapse in early stages of ALS-FUS results in synaptic impairment, potentially representing an initial trigger of neurodegeneration.
Group and Individual Level Variations between Symmetric and Asymmetric DLPFC Montages for tDCS over Large Scale Brain Network Nodes
Authors: Soleimani Ghazaleh , Saviz Mehrdad , Bikson Marom , Towhidkhah Farzad , Kuplicki Rayus , Paulus Martin P. , Ekhtiari Hamed
Published: June 2020

Two challenges to optimizing transcranial direct current stimulation (tDCS) are selecting between, often similar, electrode montages and accounting for inter-individual differences in response. These two factors are related by how tDCS montage determines current flow through the brain considered across or within individuals. MRI-based computational head models (CHMs) predict how brain anatomy determine electric field (EF) patterns for a given tDCS montage. Because conventional tDCS produces diffuse brain current flow, stimulation outcomes may be understood as modulation of global networks. Therefore, we developed network-led, rather than region-led, approach. We specifically considered two common frontal tDCS montages that nominally target the dorsolateral prefrontal cortex; asymmetric unilateral (anode/cathode: F4/Fp1) and symmetric bilateral (F4/F3) electrode montages. CHMs of 66 participants were constructed. We showed that cathode location significantly affects EFs in the limbic network. Furthermore, using a finer parcellation of large-scale networks, we found significant differences in some of main nodes within a network, even if there is no difference at the network level. This study generally demonstrates a methodology for considering the components of large-scale networks in CHMs instead of targeting a single region and specifically provides insight into how symmetric vs asymmetric frontal tDCS may differentially modulate networks across a population.
Entraining corticocortical plasticity changes oscillatory activity in action control and inhibition
Authors: Sel Alejandra , Verhagen Lennart , Angerer Katharina , David Raluca , Klein-Flügge Miriam , Rushworth Matthew
Published: June 2020

Oscillatory activity may reflect interactions between brain areas[1]. Here we tested whether inducing corticocortical plasticity in a specific set of connections changes oscillatory activity and cortico-cortical interactions and, if this is the case, whether the changes manifest in a manner that is behaviour state-dependent. We either increased or decreased the influence of activity in human ventral premotor cortex (PMv) over activity in primary motor cortex (M1) using cortico-cortical paired associative stimulation (ccPAS)[2, 3]. Before and after stimulation participants performed a Go/No-Go task. While M1 TMS pulses revealed the excitatory state of the motor system at specific time points, the electroencephalogram (EEG) revealed the evolution of oscillatory activity dynamics in the motor system over several hundreds of milliseconds before, during, and after each movement. Augmenting cortical connectivity between PMv and M1, by evoking synchronous pre- and postsynaptic activity in the PMv-M1 pathways, led to a state-dependent modulation of the causal influence of PMv over M1, and at the same time, enhanced oscillatory beta and theta rhythms in Go and No-Go trials, respectively. No changes were observed in the alpha rhythm. The plasticity induction effect was dependent on PMv-M1 stimulation order; the opposite patterns of results were observed after an equal amount of stimulation of PMv and M1 but applied in a temporal pattern that did not augment PMv’s influence over M1. These results are consistent with Hebbian principles of synaptic plasticity[4] and show that artificial manipulation of cortico-cortical connectivity produces state-dependent functional changes in the spectral fingerprints of the motor circuit.
Disentangling principled and opportunistic motives for reacting to injustice: A genetically-informed exploration of justice sensitivity
Authors: Eftedal Nikolai Haahjem , Kleppestø Thomas Haarklau , Czajkowski Nikolai Olavi , Sheehy-Skeffington Jennifer , Røysamb Espen , Vassend Olav , Ystrom Eivind , Thomsen Lotte
Published: June 2020

Moral judgments may be driven by both principled and opportunistic motivations. Being morally principled is to consistently adhere to a single set of rules about morality and justice. Opportunistic morality rather involves selectively enforcing rules when they are beneficial to one’s interests. These two kinds of motivations sometimes pull in the same direction, other times not. Prior studies on moral motivations have mostly focused on principled morality. Opportunistic morality, along with its phenotypic and genetic correlates, remains largely unexamined. Here, utilizing a sample from the Norwegian Twin Registry, consisting of 312 monozygotic-and 298 dizygotic twin pairs (N = 1220), we measure people’s propensity to react to injustice as victims, observers, beneficiaries, and perpetrators of injustice, using the Justice Sensitivity scale. Our genetically informative sample allows a biometric modeling approach that provides increased stringency in inferring latent psychological traits. We find evidence for two substantially heritable traits explaining correlations between Justice Sensitivity facets, which we interpret as aprincipled justice sensitivity(h2= .45) leading to increased sensitivity to injustices of all categories, and anopportunistic justice sensitivity(h2= .69) associated with increased victim sensitivity and a decreased propensity to feel guilt from being a perpetrator. These heritable justice traits share a genetic substrate with broad strategies for cooperation (as measured by altruism and trust) and for selectively benefitting oneself over the adaptive interests of others (as measured by social dominance orientation and support for monopolizing territory and resources), and differ genetically and phenotypically from Big Five personality traits.
Eukarion-134 attenuates endoplasmic reticulum stress-induced mitochondrial dysfunction in human skeletal muscle cells
Authors: Thoma Anastasia , Lyon Max , Al-Shanti Nasser , Nye Gareth A , Cooper Robert G , Lightfoot Adam P
Published: June 2020

Maladaptive endoplasmic reticulum (ER) stress is associated with modified reactive oxygen species (ROS) generation, altered mitochondrial bioenergetics, and oxidative damage; and is postulated as a potential mechanism involved in the underlying muscle weakness experienced by patients with myositis, an acquired autoimmune neuromuscular disease. In this study, we investigate the impact of ROS generation in anin vitromodel of ER stress in skeletal muscle, using the ER stress inducer tunicamycin (24 hours) in presence or absence of a superoxide dismutase/catalase mimetic Eukarion (EUK)-134. ER stress activation, ROS generation, mitochondrial function, biogenesis, morphology and dynamics (fusion/fission) were examined. Tunicamycin induced maladaptive ER stress, validated by stimulation of GRP94, GRP78, CHOP, XBP-1, ERDJ4, and GADD34, which were mostly mitigated by EUK-134 at transcriptional level. ER stress triggered mitochondrial unfolded protein response and promoted mitochondrial dysfunction, described by substantial loss of mitochondrial membrane potential, as well as reduction of respiratory control ratio, reserve capacity, phosphorylating respiration, and coupling efficiency, which was ameliorated by EUK-134. ROS-mediated biogenesis and fusion of mitochondria was evident in presence of tunicamycin, which however, had high propensity of fragmentation, accompanied by upregulated mRNA levels of fission-related markers. Increased cellular ROS generation oxidative stress was observed in response to ER stress that was ameliorated in the presence of EUK-134, even though no changes in mitochondrial superoxide were noticeable. These findings suggest that targeting ROS generation using the superoxide dismutase/catalase mimetic EUK-134 can amend aspects of ER stress-induced changes in mitochondrial dynamics and function. Overall, this study suggests that in instances of chronic ER stress, such as in myositis, quenching ROS generation may be a promising therapy for muscle weakness and dysfunction.
Does the Freeze-all strategy improve the cumulative live birth rate and the time to become pregnant in IVF cycles?
Authors: Johnson S. , Vandromme J. , Larbuisson A. , Raick D. , Delvigne A.
Published: June 2020

Introduction

Freezing of all good quality embryos and their transfer in subsequent cycles, named the freeze-all strategy (FAS), is widely used for ovarian hyperstimulation syndrome (OHSS) prevention. Indeed, it increases live birth rates among high responders and prevents preterm birth and small for gestational age. Consequently, why shouldn’t we extend it to all?

Materials and methods

A retrospective and monocentric study was conducted between January 2008 and January 2018 comparing the cumulative live birth rates (CLBR) between patients having undergone FAS and a control group using fresh embryo transfer (FET) and having at least one frozen embryo available. Analyses were made for the entire cohort (population 1) and for different subgroups according to confounding factors selected by a logistic regression (population 3), and to the BELRAP (Belgian Register for Assisted Procreation) criteria (population 2).

Results

2216 patients were divided into two groups: Freeze all (FA), 233 patients and control (C), 1983 patients. The CLBR was 50.2% vs 58.1% P=0.021 for population 1 and 53.2% vs 63.3% P=0.023 for population 2, including 124 cases and 1241 controls. The CLBR stayed in favour of the C group: 70.1% vs 55.9% P=0.03 even when confounding variables were excluded (FA and C group respectively 109 and 770 patients). The median time to become pregnant was equally in favour of the C group with a median of 5 days against 61 days.

Conclusions

CLBR is significantly lower in the FA group compared to the C group with a longer time to become pregnant. Nevertheless, the CLBR in the FA group remains excellent and superior to that observed in previous studies with similar procedures and population. These results confirm the high efficiency of FAS but underline the necessity to restrict the strategy to selected cases.
Light-activated signaling in DNA-encoded sender-receiver architectures
Authors: Yang Shuo , Pieters Pascal A. , Joesaar Alex , Bögels Bas W.A. , Brouwers Rens , Myrgorodska Iuliia , Mann Stephen , de Greef Tom F.A.
Published: June 2020

Collective decision making by living cells is facilitated by exchange of diffusible signals where sender cells release a chemical signal that is interpreted by receiver cells. Biologists have started to unravel the underlying physicochemical determinants that control the effective communication distance using genetically modified cells. However, living systems are inherently challenging to manipulate and study systematically and quantitatively. Therefore, the development of generic and tunable abiotic mimics featuring compartmentalized signaling is highly desirable. Here, by adapting a previously reported artificial cell-cell communication system, we engineer DNA-encoded sender-receiver architectures, where protein-polymer microcapsules act as cell mimics and molecular communication occurs through diffusive DNA signals. We prepare spatial distributions of sender and receiver protocells using a microfluidic trapping array, and setup a signaling gradient from a single sender cell using light, which activates surrounding receivers through DNA strand displacement. Our systematic analysis reveals how the effective signal range of a single sender is determined by various factors including the density and permeability of receivers, extracellular signal degradation, signal consumption and catalytic regeneration. In addition, we construct a three-population configuration where two sender cells are embedded in a dense array of receivers that implement Boolean logic and investigate spatial integration of non-identical input cues. The results advance our understanding of diffusion-based sender-receiver topologies and present a strategy for constructing spatially controlled chemical communication systems that have the potential to reconstitute collective cellular behavior.
Direct energy transfer from photosystem II to photosystem I is the major regulator of winter sustainability of Scots pine
Authors: Bag Pushan , Chukhutsina Volha , Zhang Zishan , Paul Suman , Ivanov Alexander G. , Shutova Tatyana , Croce Roberta , Holzwarth Alfred R. , Jansson Stefan
Published: June 2020

Evergreen conifers in boreal forests can survive extremely cold (freezing) temperatures during the long dark winter and fully recover during the summer. A phenomenon called ‘sustained quenching’ putatively provides photoprotection and enables their survival, but its precise molecular and physiological mechanisms are not understood. To unveil them, we have analyzed the seasonal adaptation of the photosynthetic machinery of Scots pine (Pinus sylvestris) trees by monitoring multi-year changes in weather, chlorophyll fluorescence, chloroplast ultrastructure, and changes in pigment-protein composition. Recorded Photosystem II and Photosystem I performance parameters indicate that highly dynamic structural and functional seasonal rearrangements of the photosynthetic apparatus occur. Although several mechanisms might contribute to ‘sustained quenching’ of winter/early spring pine needles, time-resolved fluorescence analysis shows that extreme down-regulation of photosystem II activity along with direct energy transfer from photosystem II to photosystem I plays a major role. This mechanism is enabled by extensive thylakoid destacking allowing for mixing of PSII with PSI complexes. These two linked phenomena play crucial roles in winter acclimation and protection.

Graphical abstract
Annexin a2 as a target protein for chlorogenic acid in human lung cancer A549 cells
Authors: Wang Lei , Du Hongwu , Chen Peng
Published: June 2020

Chlorogenic acid, an important active component of coffee with anti-tumor activities, has been found for many years. However, the lack of understanding about its target proteins greatly limits the exploration of its anti-tumor molecular mechanism and clinical application. Here, in vitro and animal experiments showed that chlorogenic acid had a significant inhibitory effect on the proliferation of A549 cells. Using the spontaneous fluorescence characteristic of chlorogenic acid to screen the target proteins cleverly to avoid the problem of chemical modification increasing false positive, we identify and verify annexin A2 (ANXA2) as a covalent binding target of chlorogenic acid in A549 cells. Then, we discover that chlorogenic acid as an inhibitor of the binding of ANXA2 to p50 subunit inhibited the expression of downstream anti-apoptotic genes cIAP1 and cIAP2 of NF-κB signaling pathway in A549 cells in vitro and vivo. Moreover, we find chlorogenic acid hindered the binding of ANXA2 and actin maybe involved in the impediment of tumor cell cycle and migration. Thus, this work demonstrates that chlorogenic acid, as a binding ligand of ANXA2, decrease the expression of NF-κB downstream anti-apoptotic genes, inhibiting the proliferation of A549 cells in vivo and vitro.
Strain Level Microbial Detection and Quantification with Applications to Single Cell Metagenomics
Authors: Zhu Kaiyuan , Robinson Welles , Schäffer Alejandro A. , Xu Junyan , Ruppin Eytan , Ergun A. Funda , Ye Yuzhen , Sahinalp S. Cenk
Published: June 2020

The identification and quantification of microbial abundance at the species or strain level from sequencing data is crucial for our understanding of human health and disease. Existing approaches for microbial abundance estimation either use accurate but computationally expensive alignment-based approaches for species-level estimation or less accurate but computationally fast alignment-free approaches that fail to classify many reads accurately at the species or strain-level.

Here we introduceCAMMiQ, a novel combinatorial solution to the microbial identification and abundance estimation problem, which performs better than the best used tools on simulated and real datasets with respect to the number of correctly classified reads (i.e., specificity) by an order of magnitude and resolves possible mixtures of similar genomes.

As we demonstrate,CAMMiQcan better distinguish between single cells deliberately infected with distinctSalmonellastrains and sequenced using scRNA-seq reads than alternative approaches. We also demonstrate thatCAMMiQis also more accurate than the best used approaches on a variety of synthetic genomic read data involving some of the most challenging bacterial genomes derived from NCBI RefSeq database; it can distinguish not only distinct species but also closely related strains of bacteria.

The key methodological innovation ofCAMMiQis its use of arbitrary length, doubly-unique substrings, i.e. substrings that appear in (exactly) two genomes in the input database, instead of fixed-length, unique substrings. To resolve the ambiguity in the genomic origin of doubly-unique substrings,CAMMiQemploys a combinatorial optimization formulation, which can be solved surprisingly quickly.CAMMiQ’s index consists of a sparsified subset of the shortest unique and doubly-unique substrings of each genome in the database, within a user specified length range and as such it is fairly compact. In short,CAMMiQoffers more accurate genomic identification and abundance estimation than the best used alternatives while using similar computational resources.

Availability

https://github.com/algo-cancer/CAMMiQ
Extensive individual differences of category information in ventral temporal cortex in the congenitally blind
Authors: Rosenke M. , Van den Hurk J. , Margalit E. , Op de Beeck H. P. , Grill-Spector K. , Weiner K. S.
Published: June 2020

Human ventral temporal cortex (VTC) is a cortical expanse that performs different functions and computations, but is especially critical for visual categorization. Nevertheless, accumulating evidence shows that category-selective regions persist in VTC in the absence of visual experience – for example, in congenitally blind (CB) participants. Despite this evidence, a large body of previous work comparing functional representations in VTC between sighted and CB participants performed univariate analyses at the group level, which assume a homogeneous population – an assumption that has not been formally tested until the present study. Specifically, using fMRI in CB and sighted participants (male and female), we empirically show that at the group level, distributed category representations in VTC are more reliable in the sighted (when viewing visual stimuli) compared to the CB (when hearing auditorily-substituted visual stimuli). Despite these group differences, there is extensive heterogeneity in VTC category representations in the CB to the point that VTC category representations in a subset of CB participants (some who were born without eyes, but not all) are more similar to sighted individuals compared to other CB participants. Together, our findings support a novel idea that driving factors contributing to the formation of VTC category representations in the blind are subject-specific, which complements factors that may generalize across group members. More broadly, the present findings caution conclusions of homogeneity across subjects within a group when performing group neuroimaging analyses without explicitly quantifying individual differences.
Generating a skin-based meta-model for compliant parts in composite material: numerical and experimental results
Authors: Polini Wilma , Corrado Andrea
Published: June 2020

Purpose

The purpose of this paper is to present a skin-based approach able to generate the variability model for a component in composite material due to its manufacturing process. It generates a skin-based model of the manufactured part. The skin model discretizes the part surfaces by points to take into account the geometric deviations, those points are the nodes of finite element analysis used for tolerance analysis of compliant assemblies.

Design/methodology/approach

The paper presents a general and systematic simulation model for generating a variability meta-model for a component in composite material due to its manufacturing process. The model is constituted by three steps: definition and pre-processing of the nominal model, generation of the manufacturing process model and evaluation of the part variability.

Findings

The advantage of this approach is related to the fact that it is designed as a part of a digital process that establishes a continuous and unambiguous flow of variation information from the part design to manufacturing and assembly and that takes into account the manufacturing signature. This is its uniqueness compared to other simulation approaches focused only on manufacturing.

Research limitations/implications

Considering the variability around the nominal value of all the process parameters and parts with more complex geometries are not taken into account now, which will be modelled in practical applications.

Practical implications

To properly manage uncertainty since conceptual design of complex product, next generation geometry assurance requires simulation models to realistically consider process signatures due to the manufacturing process. This work focusses on this next generation tool for geometry assurance.

Originality/value

The literature is focused on metal sheets joined by welding or riveting. There are other materials widely used and typically compliant: the composite materials that typically used mechanical fixing elements (bolting, riveting) and structural adhesives to joint parts. No software tools exist in the literature to deal with uncertainty from manufacturing to assembly processes in products made by composite. This is the reason of the present work.
Personality traits, teamwork competencies and academic performance among first-year engineering students
Authors: Tang Kuok Ho Daniel
Published: June 2020

Purpose

It is commonly believed that personality traits determine a person's ability to work in a team and academic performance. However, studies have shown inconsistent results with some personality traits better than the other in predicting students' performance in different academic majors. The purpose of this study is to examine the interrelation between personality traits, teamwork competencies and academic performance among first-year first semester engineering students in an Australian university located in the Sarawak state of Malaysia.

Design/methodology/approach

The Individual and Team Performance (ITP) metrics were administered among 189 students to gauge their personality traits as well as self-rated and peer-rated teamwork competencies. The correlations between personality traits and teamwork competencies as well as correlations of both the variables to academic performance were subsequently analyzed.

Findings

This study shows no significant difference between the self-rated and peer-rated teamwork competencies. Adventurous trait appears to negatively correlate with teamwork competencies. This study also reveals teamwork competencies as better predictors of academic performance than personality traits. Commitment and focus show relatively larger effect on academic performance. It can be concluded that commitment is the most significant factor to excel in first-year engineering in the university. Therefore, interventions that promote commitment is crucial to academic performance of the first-year first semester engineering students.

Practical implications

This study promulgates the development of team competencies which are more crucial to academic excellence than personalities. It is useful for the design of team learning activities which lead to the development of teamwork competencies while improving academic performance. It shows that team activities which reinforce commitment especially and focus secondarily, will have significant positive effect on academic performance of the first-year engineering students generally.

Originality/value

While most studies in this area examine the correlation between personality traits and academic performance, this study is among the very few that looks into the aspect of teamwork competencies. This study also finds its value in its regional significance as such correlational studies are not prevalent in Malaysia.
Mobile landscapes and transport tourism: the visual experience of mobility during cruises and coach tours
Authors: Rhoden Steven , Kaaristo Maarja
Published: June 2020

Purpose

This study aims to analyze the visual aspects of transport tourists’ experience of mobility focusing on British cruise and coach tourists’ international travel experiences.

Design/methodology/approach

The qualitative data was collected using semi-structured in-depth interviews with coach and cruise tourists and analyzed using thematic analysis.

Findings

The visual experience of mobility (demonstrated in the paper by the example of cruises and coach tours) is critical in the formation of transport tourism experiences. The mobile tourist landscapes emerge from the interplay of the subjective experiences of particular modes of mobility (vehicle or vessel) and routes, whereby the two key visual elements are the changing scenery and views of everyday local life as experienced whilst traveling.

Research limitations/implications

The present study focuses particularly on the visual elements of passive transport tourism experiences. It does not account for other tourist activities nor does it study the experiences associated with active transport tourism. Future research could perform a holistic analysis of tourists’ experiences of transport in all its forms.

Practical implications

The findings point to the centrality of the experience of mobility in transport tourism experience. The following two key aspects of the experience emerged: the importance of variation of the scenery that the tourist consumes during their tour and a desire to observe mundane, everyday life elements of the destination, which should be taken into account by the tour operators and service providers in the route design and marketing.

Originality/value

Coach and cruise tourism are rarely analyzed together; this study demonstrates considerable parallels between the two in considering them as transport tourism, a mode of recreational activity where mobility is the central part of the tourist experience and should, therefore, be considered a tourist attraction in and of itself.
Stakeholders’ perceptions of sustainable development of higher education institutions: an intellectual capital approach
Authors: Pedro Eugénia de Matos , Leitão João , Alves Helena
Published: June 2020

Purpose

This study aims to identify stakeholders’ perceptions of the effects associated with different components of intellectual capital (IC) on the sustainable development (SD) practices of higher education institutions (HEIs).

Design/methodology/approach

The empirical approach uses a structural equation model to provide new empirical findings in relation to 738 students and 587 lecturers/researchers at seven Portuguese state HEIs through quantitative research.

Findings

The results obtained are, firstly, important contributions to the literature on the IC and SD practices of HEIs, as a relationship between these two constructs is confirmed, especially through relational capital (RC) and structural capital (SC). Secondly, the stakeholders considered show different perceptions of the influence of the components of HEIs’ IC on these institutions’ SD practices, and thirdly, perception of the economic dimension is most influenced.

Practical implications

The empirical findings indicate the need to provide better information about HEIs’ policies and practices of SD and how the latter contribute to the SD of the institution and its region of influence.

Originality/value

No previous studies investigate students and teachers/researchers’ perceptions of the social, environmental, economic and organizational dimensions of SD in HEIs and at the same time how those perceptions can be influenced by the components of IC (e.g. human capital, SC, RC) in that institution.