bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing temperature-dependent competition between two invasive mosquito species
Authors: Evans Michelle V , Drake John M , Jones Lindsey , Murdock Courtney C
Published: June 2020

Invasive mosquitoes are expanding their ranges into new geographic areas and interacting with resident mosquito species. Understanding how novel interactions can affect mosquito population dynamics is necessary to predict transmission risk at invasion fronts. Mosquito life-history traits are extremely sensitive to temperature and this can lead to temperature-dependent competition between competing invasive mosquito species.

We explored temperature-dependent competition betweenAedes aegyptiandAnopheles stephensi, two invasive mosquito species whose distributions overlap in India, the Middle East, and North Africa. We followed mosquito cohorts raised at different intraspecific and interspecific densities across five temperatures (16°C - 32°C) to measure traits relevant for population growth and to estimate species' per capita growth rates. We then used these growth rates to derive each species competitive ability at each temperature.

We find strong evidence for asymmetric competition at all temperatures, withAe. aegyptiemerging as the dominant competitor. This was primarily due to differences in larval survival and development times across all temperatures that resulted in a higher estimated intrinsic growth rate and competitive tolerance estimate forAe. aegypticompared toAn. stephensi.

Synthesis and applications:The spread ofAn. stephensiinto the African continent could lead to urban transmission of malaria, an otherwise rural disease, increasing the human population at risk and complicating malaria elimination efforts. Competition has resulted in habitat segregation of other invasive mosquito species, and our results suggest that it may play a role in determining the distribution ofAn. stephensiacross its invasive range.
Stressful times in a climate crisis: how will aphids respond to more frequent drought?
Authors: Leybourne Daniel Joseph , Preedy Katharine F , Valentine Tracy A , Bos Jorunn IB , Karley Alison J
Published: June 2020

Aim

Aphids are abundant in natural and managed vegetation, supporting a diverse community of organisms and causing damage to agricultural crops. Using a meta-analysis approach, we aimed to advance understanding of how increased drought incidence will affect this ecologically and economically important insect group, and to characterise the underlying mechanisms.

Location

Global.

Time period

1958–2020.

Major taxa studied

Aphids.

Methods

We used qualitative and quantitative synthesis techniques to determine whether drought stress has a negative, positive, or null effect on aphid fitness. We examined these effects in relation to 1) aphid biology, 2) the aphid-plant. species combination. We compiled two datasets: 1) a “global” dataset (n = 55 from 55 published studies) comprising one pooled effect size per study, and 2) an “expanded” dataset (n = 93) containing multiple datapoints per study, separated into different measures of aphid fitness but pooled across aphid-plant combinations. Where reported, we extracted data on the effect of drought on plant vigour, and plant tissue concentrations of nutrients and defensive compounds, to capture the potential causes of aphid responses.

Results

Across all studies (“global” dataset), drought stress had a negative effect on aphid fitness: Hedges’ g = −0.57; 95% confidence interval (CI95) = ±0.31. The “expanded” dataset indicated that, on average, drought stress reduced aphid fecundity (g = − 0.98; CI95 = ±0.50) and increased development time (g = 1.13; CI95 = ±1.02). Furthermore, drought stress had a negative impact on plant vigour (g = −7.06; CI95 = ±2.86) and increased plant concentrations of defensive chemicals (g = 3.14; CI95 = ±3.14).

Main conclusions

Aphid fitness is typically reduced under drought, associated with reduced plant vigour and increased chemical defence in drought-stressed plants. We propose a conceptual model to predict drought effects on aphid fitness in relation to plant vigour and defence.
Neural Flip-Flops II: The Role of Cascaded Oscillators in Short-Term Memory, EEGs, and Epilepsy
Authors: Yoder Lane
Published: June 2020

By enabling many brain structures’ state changes, the explicit cascaded oscillators proposed here can generate the rhythmic neural activity found in EEGs. The function of such synchronization in information processing systems is timing error avoidance. The narrow requirement for the oscillator input pulse duration suggests a possible relationship to the abnormal electrical activity characteristic of epileptic seizures. Together, flip-flops and synchronization by oscillators suggest a resolution to the longstanding controversy of whether short-term memory depends on neurons firing persistently or in brief, coordinated bursts.

The proposed cascade of oscillators consists of a ring oscillator and four toggle flip-flops connected in sequence. The novel oscillator and toggle are composed of three and six neurons, respectively. Their operation depends only on minimal properties of excitatory and inhibitory inputs.

The hypothesis that cascaded oscillators produce EEG phenomena implies that the distribution of EEG frequencies is determined by just two parameters, the mean (μd) and standard deviation (σd) of the delay times of neurons that make up the initial oscillators in the cascades. For example, if μdand σdare measured in milliseconds, the boundary separating the alpha and beta frequency bands is

With 4 and 1.5 ms being the best available estimates for μdand σd, respectively, this predicted boundary value is 14.9 Hz, which is within the range of commonly cited estimates obtained empirically from EEGs. Four and 1.5 ms also accurately predict the peaks and other boundaries of the five major EEG frequency bands.

Significance statement

The neuronal model proposed here implies several major aspects of electroencephalography. The matched periods of neural activity found in EEGs, and their wide distribution across the brain and across the frequency spectrum, follow from selective pressure for a biologically useful function: timing error avoidance for diverse brain functions in the trade-off between speed and accuracy. This activity can be achieved with a simple organization of synaptic connections and minimal neuron capabilities of excitation and inhibition. The multimodal distribution of EEG frequencies is an explicit function of the mean and variance of neuron delay times. The model suggests a relationship to epileptic seizures and a resolution to a short-term memory controversy. Two EEG characteristics make other models implausible.
Toll like Receptor signalling byPrevotella histicolaactivates alternative NF-κB signalling in Cystic Fibrosis bronchial epithelial cells compared toP.aeruginosa
Authors: Bertelsen A. , Elborn J.S. , Schock B.C.
Published: June 2020

Cystic Fibrosis (CF), caused by mutations affecting theCFTRgene, is characterised by viscid secretions in multiple organ systems. CF airways contain thick mucus, creating a gradient of hypoxia, which promotes the establishment of polymicrobial infection. Such inflammation predisposes to further infection, a self-perpetuating cycle in mediated by NF-κB. Anaerobic Gram-negativePrevotellaspp. are found in sputum from healthy volunteers and CF patients and in CF lungs correlate with reduced levels of inflammation.Prevotella histicola (P.histicola)can suppress murine lung inflammation, however, no studies have examined the role ofP.histicolain modulating infection and inflammation in the CF airways. We investigated innate immune signalling and NF-kB activation in CF epithelial cells CFBE41o-in response to clinical stains ofP.histicolaandPseudomonas aeruginosa(P.aeruginosa). Toll-Like Receptor (TLR) expressing HEK-293 cells and siRNA assays for TLRs and IKKa were used to confirm signalling pathways.

We show thatP.histicolainfection activated the alternative NF-kB signalling pathway in CF bronchial epithelial cells inducing HIF-1α protein. TLR5 signalling was responsible for the induction of the alternative NF-kB pathway through phosphorylation of IKKα. The induction of transcription factor HIF-1α was inversely associated with the induction of the alternative NF-kB pathway and knockdown of IKKα partially restored canonical NF-kB activation in response toP.histicola.

This study demonstrates that different bacterial species in the respiratory microbiome can contribute differently to inflammation, either by activating inflammatory cascades (P.aeruginosa) or by muting the inflammatory response by modulating similar or related pathways (P.histicola). Further work is required to assess the complex interactions of the lung microbiome in response to mixed bacterial infections and their effects in people with CF.
Shared and unique brain network features predict cognition, personality and mental health in childhood
Authors: Chen Jianzhong , Tam Angela , Kebets Valeria , Orban Csaba , Ooi Leon Qi Rong , Marek Scott , Dosenbach Nico , Eickhoff Simon , Bzdok Danilo , Holmes Avram J , Thomas Yeo B.T.
Published: June 2020

The manner through which individual differences in brain network organization track population-level behavioral variability is a fundamental question in systems neuroscience. Recent work suggests that resting-state and task-state functional connectivity can predict specific traits at the individual level. However, the focus of most studies on single behavioral traits has come at the expense of capturing broader relationships across behaviors. Here, we utilized a large-scale dataset of 1858 typically developing children to estimate whole-brain functional network organization that is predictive of individual differences in cognition, impulsivity-related personality, and mental health during rest and task states. Predictive network features were distinct across the broad behavioral domains: cognition, personality and mental health. On the other hand, traits within each behavioral domain were predicted by highly similar network features. This is surprising given decades of research emphasizing that distinct brain networks support different mental processes. Although tasks are known to modulate the functional connectome, we found that predictive network features were similar between resting and task states. Overall, our findings reveal shared brain network features that account for individual variation within broad domains of behavior in childhood, yet are unique to different behavioral domains.
Hippocampal-Prefrontal Interactions during Spatial Decision-Making
Authors: Tavares Lucas CS , Tort Adriano BL
Published: June 2020

The hippocampus has been linked to memory encoding and spatial navigation, while the prefrontal cortex is associated with cognitive functions such as decision-making. These regions are hypothesized to communicate in tasks that demand both spatial navigation and decision-making processes. However, the electrophysiological signatures underlying this communication remain to be better elucidated. To investigate the dynamics of the hippocampal-prefrontal interactions, we have analyzed their local field potentials and spiking activity recorded from rats performing an odor-cued spatial alternation task in an 8-shaped maze. We found that the phase coherence of theta peaked around the choice point area of the maze. Moreover, Granger causality revealed a hippocampus->prefrontal cortex directionality of information flow at theta frequency, peaking at starting areas of the maze, and on the reverse direction at delta frequency, peaking near the turn onset. Additionally, the patterns of phase-amplitude cross-frequency coupling within and between the regions also showed spatial selectivity, and a new method revealed that hippocampal theta and prefrontal delta modulated not only gamma amplitude but also inter-regional gamma synchrony. Lastly, we found that the theta rhythm dynamically modulated neurons in both regions, with the highest modulation at the choice area; interestingly, prefrontal cortex neurons were more strongly modulated by the hippocampal theta rhythm than by their local field rhythm. In all, our results reveal maximum electrophysiological interactions between the hippocampus and the prefrontal cortex near the decision-making period of the spatial alternation task. These results corroborate the hypothesis that a dynamic interplay between these regions takes place during spatial decisions.
Evaluation of origin of driving force for loop formation in a chromatin fiber
Authors: Yokota Hiroshi , Tachikawa Masashi
Published: June 2020

Chromosome condensation results from the formation of consecutive chromatin loops in which excluded volume interactions lead to chromosome stiffness. Formation of chromatin loops requires energy, but the source of such energy remains controversial. Here, we quantified the energy balance during chromatin loop formation by calculating the free energies of unlooped and looped chromatins using a lattice model of polymer chains. We tested two hypothetical energy sources: thermal fluctuation and ATP hydrolysis. We evaluated the free energy difference of the chain loop model without accounting for excluded volume interactions (phantom loop model), and integrated those interactions by employing the mean-field theory (interacting loop model), where we introduced the parameter of excluded volume interaction within a single loopvex. Using our strategy, we confirmed that loop-growth efficiency calculated by the phantom loop model is too high to explain the experimental data. Comparing loop-growth efficiencies for each energy source, and using the interacting loop model, we found that excluded volume interaction is essential for chromatin’s resistance to looping, regardless of the energy source. We predict that the quantitative measurement ofvexdetermines which energy source is more plausible.

Author summary

Before mitosis, the chromatin fibers of eukaryotic cells fold into consecutive loop structures and condense into rod-like chromosomes. Chromosome stiffness results from the interaction of the excluded volume between chromatin loops. The driving force of loop formation and growth is still controversial, despite the many efforts undertaken to clarify it. Two possible origins can be considered: the energy provided by thermal fluctuations or the energy gained from ATP hydrolysis. To discuss the validity of each, we constructed a theoretical model of chromatin loop formation that includes excluded volume interactions. Using this model, we calculated the free energy difference before and after chromatin loop formation, which corresponds to the energy that fuels chromatin looping. By comparing the results for each energy source, we conclude that the spatial distribution of chromatin loops should be relatively wide, given the large excluded volume interaction within a single loop, irrespective of which energy source is valid. Moreover, our results imply that intra-loop interactions are key to determine the driving force of chromatin loop formation.
Transgenerational fitness effects of lifespan extension by dietary restriction inCaenorhabditis elegans
Authors: Ivimey-Cook Edward R. , Sales Kris , Carlsson Hanne , Immler Simone , Chapman Tracey , Maklakov Alexei A.
Published: June 2020

Dietary restriction increases lifespan in a broad variety of organisms and improves health in humans. However, long-term transgenerational consequences of dietary interventions are poorly understood. Here we investigated the effect of dietary restriction by temporary fasting (TF) on mortality risk, age-specific reproduction and fitness across three generations of descendants inC. elegans. We show that while TF robustly reduces mortality risk and improves late-life reproduction in the parental generation (P0), it has a wide range of both positive and deleterious effects on future generations (F1-F3). Remarkably, great-grandparental exposure to TF in early-life reduces fitness and increases mortality risk of F3descendants to such an extent that TF no longer promotes a lifespan extension. These findings reveal that transgenerational trade-offs accompany the instant benefits of dietary restriction underscoring the need to consider fitness of future generations in pursuit of healthy ageing.
Consistent marine biogeographic boundaries across the tree of life despite centuries of human impacts
Authors: Holman Luke E. , de Bruyn Mark , Creer Simon , Carvalho Gary , Robidart Julie , Rius Marc
Published: June 2020

Over millennia, ecological and evolutionary mechanisms have shaped macroecological distributions across the tree of life. Research describing patterns of regional and global biogeography has traditionally focussed on the study of conspicuous species. Consequently, there is limited understanding of cross-phyla biogeographic structuring, and an escalating need to understand the macroecology of both microscopic and macroscopic organisms. Here we used environmental DNA (eDNA) metabarcoding to explore the biodiversity of marine metazoans, micro-eukaryotes and prokaryotes along an extensive and highly heterogeneous coastline. Our results showed remarkably consistent biogeographic structure across the kingdoms of life, which were underpinned by environmental and anthropogenic influence. Additionally, metazoan communities displayed biographic patterns that suggest regional biotic homogenisation of conspicuous species. Against the backdrop of global pervasive anthropogenic environmental change, our work highlights the importance of considering multiple domains of life to understand the maintenance and drivers of marine biodiversity across broad taxonomic, ecological and geographical scales.
Wolbachia-conferredantiviral protection is determined by developmental temperature
Authors: Chrostek Ewa , Martins Nelson , Marialva Marta S , Teixeira Luis
Published: June 2020

Wolbachiais a maternally transmitted bacterium widespread in arthropods and filarial nematodes, and confers strong antiviral protection inDrosophila melanogasterand other insects.Wolbachia-transinfectedAedes aegyptiare currently being deployed to fight transmission of dengue and Zika viruses. However, the mechanism of antiviral protection and factors influencing it are still not fully understood. Here we show that temperature modulatesWolbachia-conferred protection inDrosophila melanogaster. Temperature after infection directly impactsDrosophilaC virus replication and modulatesWolbachiaprotection. At higher temperatures virus proliferates more and is more lethal, whileWolbachiaconfers lower protection. Strikingly, host developmental temperature is a determinant ofWolbachia-conferred antiviral protection. While there is a strong protection when flies are raised from egg to adult at 25°C, the protection is highly reduced or completely abolished when flies develop at 18°C. However,Wolbachia-induced changes during development are not sufficient to limit virus-induced mortality, asWolbachiais still required to be present in adults at the time of infection. This developmental effect is general, since it was present in different host genotypes,Wolbachiavariants and upon infection with different viruses. Overall, we show thatWolbachia-conferred antiviral protection is temperature dependent, being present or absent depending on the environmental conditions. This interaction likely impactsWolbachia-host interactions in nature and, as a result, frequencies of host and symbionts in different climates. Dependence ofWolbachia-mediated pathogen blocking on developmental temperature could be used to dissect the mechanistic bases of protection and should be considered by programmes deployingWolbachiaas an antiviral agent in the field.

Significance Statement

Insects are often infected with beneficial intracellular bacteria. The bacteriumWolbachiacan protect insects from pathogenic viruses. This effect can be used to prevent transmission of dengue and Zika viruses byWolbachia-infected mosquitoes. To deployWolbachiain the field successfully and understand the biology of insects in the wild we need to discover which factors affectWolbachia-conferred antiviral protection. Here we show that the temperature in which insects develop from eggs to adults can determine presence or absence of antiviral protection. The environment, therefore, influences this insect-bacterium interaction. Our work may help to provide insights into the mechanism of viral blocking byWolbachiaand inform programs usingWolbachiain mosquito-borne disease control.
Comparative transcriptome analyses reveal genes associated with SARS-CoV-2 infection of human lung epithelial cells
Authors: Chandrashekar Darshan S. , Manne Upender , Varambally Sooryanarayana
Published: June 2020

Understanding the molecular mechanism of SARS-CoV-2 infection (the cause of COVID-19) is a scientific priority for 2020. Various research groups are working toward development of vaccines and drugs, and many have published genomic and transcriptomic data related to this viral infection. The power inherent in publicly available data can be demonstrated via comparative transcriptome analyses. In the current study, we collected high-throughput gene expression data related to human lung epithelial cells infected with SARS-CoV-2 or other respiratory viruses (SARS, H1N1, rhinovirus, avian influenza, and Dhori) and compared the effect of these viruses on the human transcriptome. The analyses identified fifteen genes specifically expressed in cells transfected with SARS-CoV-2; these includedCSF2(colony-stimulating factor 2) andS100A8andS100A9(calcium-binding proteins), all of which are involved in lung/respiratory disorders. The analyses showed that genes involved in the Type1 interferon signaling pathway and the apoptosis process are commonly altered by infection of SARS-CoV-2 and influenza viruses. Furthermore, results of protein-protein interaction analyses were consistent with a functional role of CSF2 in COVID-19 disease. In conclusion, our analysis has revealed cellular genes associated with SARS-CoV-2 infection of the human lung epithelium; these are potential therapeutic targets.
Synthesis of higher order feature codes through stimulus-specific supra-linear summation
Authors: Lyall Evan H. , Mossing Daniel P. , Pluta Scott R. , Dudai Amir , Adesnik Hillel
Published: June 2020

How cortical circuits build representations of complex objects is poorly understood. The massive dimensional expansion from the thalamus to the primary sensory cortex may enable sparse, comprehensive representations of higher order features to facilitate object identification. To generate such a code, cortical neurons must integrate broadly over space, yet simultaneously obtain sharp tuning to specific stimulus features. The logic of cortical integration that may synthesize such a sparse, high dimensional code for complex features is not known. To address this question, we probed the integration and population coding of higher order stimuli in the somatosensory and visual cortices of awake mice using two-photon calcium imaging across cortical layers. We found that somatosensory and visual cortical neurons sum highly specific combinations of sensory inputs supra-linearly, but integrate other inputs sub-linearly, leading to selective responses to higher order features. This integrative process generates a sparse, but comprehensive code for complex stimuli from the earliest stages of cortical processing. These results from multiple sensory modalities imply that input-specific supra-linear summation may represent a widespread cortical mechanism for the synthesis of higher order feature codes. This new mechanism may explain how the brain exploits the thalamocortical expansion of dimensionality to encode arbitrary complex features of sensory stimuli.
Intestinal receptor of SARS-CoV-2 in inflamed IBD tissue is downregulated by HNF4A in ileum and upregulated by interferon regulating factors in colon
Authors: Verstockt Bram , Verstockt Sare , Rahiman Saeed Abdu , Ke Bo-jun , Arnauts Kaline , Cleynen Isabelle , Sabino João , Ferrante Marc , Matteoli Gianluca , Vermeire Séverine
Published: June 2020

Patients with IBD are considered immunosuppressed, but do not seem more vulnerable for COVID-19. Nevertheless, intestinal inflammation has shown an important risk factor for SARS-CoV-2 infection and prognosis. Therefore, we investigated the effect of intestinal inflammation on the viral intestinal entry mechanisms, includingACE2, in IBD.

We collected (un)inflamed mucosal biopsies from CD (n=193) and UC (n=158) patients, and 51 matched non-IBD controls for RNA sequencing, differential gene expression and co-expression analysis. Organoids from UC patients were subjected to an inflammatory mix and processed for RNA sequencing. Transmural ileal biopsies were processed for single-cell (sc) sequencing. Publicly available colonic sc-RNA sequencing data, and microarrays from tissue pre/post anti-TNF therapy, were analyzed.

In inflamed CD ileum,ACE2was significantly decreased compared to control ileum (p=4.6E-07), whereas colonicACE2expression was higher in inflamed colon of CD/UC compared to control (p=8.3E-03; p=1.9E-03). Sc-RNA sequencing confirmed thisACE2dysregulation, and exclusive epithelialACE2expression. Network analyses highlightedHNF4Aas key regulator of ilealACE2, while pro-inflammatory cytokines and interferon regulating factors regulated colonicACE2.Inflammatory stimuli upregulatedACE2in UC organoids (p=1.7E-02), not in non-IBD controls (p=9.1E-01). Anti-TNF therapy restored colonicACE2dysregulation in responders.

Intestinal inflammation alters SARS-CoV-2 coreceptors in the intestine, with opposing effects in ileum and colon.HNF4A, an IBD susceptibility gene, is an important upstream regulator ofACE2in ileum, whereas interferon signaling dominates in colon. Our data support the importance of adequate control of IBD in order to reduce risk of (complicated) COVID-19.
CDK2 activity determines the timing of cell-cycle commitment and sequential DNA replication
Authors: Kim Sungsoo , Leong Alessandra , Nayar Chellam , Kim Minah , Yang Hee Won
Published: June 2020

To enter the cell cycle, mammalian cells must cross a point of no return (the commitment point), after which they proceed through the cell cycle regardless of changes in external signaling. This process is tightly regulated by the cyclin-dependent kinases (CDKs) and downstream molecules such as retinoblastoma (Rb). Here we show that CDK2 activity coordinates the timing of cell-cycle commitment and DNA replication. CDK4/6 activation initiates Rb phosphorylation and E2F activity, causing a gradual increase in CDK2 activity. Once CDK2 activity reaches a threshold level, CDK2 triggers the commitment point by maintaining Rb phosphorylation and subsequently initiates DNA replication. While the timing of the commitment point is tightly coupled with DNA replication, our experiments, which acutely increased CDK2 activity, suggest that the timing of the commitment point is before DNA replication. These findings highlight how cells utilize a safety mechanism to maintain genome stability by protecting against incomplete DNA replication.
Oxytocin excites BNST interneurons and inhibits BNST output neurons to the central amygdala
Authors: Francesconi Walter , Berton Fulvia , Olivera-Pasilio Valentina , Dabrowska Joanna
Published: June 2020

The dorsolateral bed nucleus of the stria terminalis (BNSTDL) has high expression of oxytocin (OT) receptors (OTR), which were shown to facilitate cued fear. However, the role of OTR in the modulation of BNSTDLactivity remains elusive. BNSTDLcontains GABA-ergic neurons classified based on intrinsic membrane properties into three types. Usingin vitropatch-clamp recordings in male rats, we demonstrate that OT selectively excites and increases spontaneous firing rate of Type I BNSTDLneurons. As a consequence, OT increases the frequency, but not amplitude, of spontaneous inhibitory post-synaptic currents (sIPSCs) selectively in Type II neurons, an effect abolished by OTR antagonist or tetrodotoxin, and reduces spontaneous firing rate in these neurons. These results suggest an indirect effect of OT in Type II neurons, which is mediated via OT-induced increase in firing of Type I interneurons. As Type II BNSTDLneurons were shown projecting to the central amygdala (CeA), we also recorded from retrogradelly labeled BNST→CeA neurons and we show that OT increases the frequency of sIPSC in these Type II BNST→CeA output neurons. In contrast, in Type III neurons, OT reduces the amplitude, but not frequency, of both sIPSCs and evoked IPSCs via a postsynaptic mechanism without changing their intrinsic excitability. We present a model of fine-tuned modulation of BNSTDLactivity by OT, which selectively excites BNSTDLinterneurons and inhibits Type II BNST→CeA output neurons. These results suggest that OTR in the BNST might facilitate cued fear by inhibiting the BNST→CeA neurons.

Highlights

Oxytocin directly excites and increases spontaneous firing of Type I BNST interneurons

Oxytocin indirectly inhibits Type II BNST neurons

Oxytocin inhibits Type II BNST output neurons to the central amygdala (BNST→CeA)

Oxytocin reduces GABA-ergic transmission in Type III BNST neurons

Oxytocin might facilitate cued fear by inhibiting the Type II BNST→CeA neurons

Graphical abstract
Vibrio campbelliichitoporin: thermostability study and implications for the development of therapeutic agents againstVibrioinfections
Authors: Aunkham Anuwat , Schulte Albert , Sim Wei Chung , Chumjan Watcharin , Suginta Wipa
Published: June 2020

Vibrio campbellii(formerlyVibrio harveyi) is a bacterial pathogen that causes vibriosis, which devastates fisheries and aquaculture worldwide.V. campbelliiexpresses chitinolytic enzymes and chitin binding/transport proteins, which serve as excellent targets for antimicrobial agent development. We previously characterizedVhChiP, a chitooligosaccharide-specific porin from the outer membrane ofV. campbelliiBAA-1116. This study employed far-UV circular dichroism and tryptophan fluorescence spectroscopy, together with single channel electrophysiology to demonstrate that the strong binding of chitoligosaccharides enhanced thermal stability ofVhChiP. The alanine substitution of Trp136at the center of the affinity sites caused a marked decrease in the binding affinity and decreased the thermal stability ofVhChiP. Tryptophan fluorescence titrations over a range of temperatures showed greater free-energy changes on ligand binding (ΔG°binding) with increasing chain length of the chitooligosaccharides. Our findings suggest the possibility of designing stable channel-blockers, using sugar-based analogs that serve as antimicrobial agents, active againstVibrioinfection.
Exofacial membrane composition and lipid metabolism regulates plasma membrane P4-ATPase substrate specificity
Authors: Roland Bartholomew P. , Jain Bhawik K. , Graham Todd R.
Published: June 2020

The plasma membrane of a cell is characterized by an asymmetric distribution of lipid species across the exofacial and cytofacial aspects of the bilayer. The regulation of membrane asymmetry is a fundamental characteristic of membrane biology, and is crucial for signal transduction, vesicle transport, and cell division. The type-IV family of P-ATPases, or P4-ATPases, establish membrane asymmetry by selection and transfer of a subset of membrane lipids from the lumenal or exofacial leaflet to the cytofacial aspect of the bilayer. It is still unclear how these enzymes sort through the spectrum of lipids within the membrane to identify their desired substrate(s) and how the membrane environment modulates this activity. Therefore, we tested how the yeast plasma membrane P4-ATPase, Dnf2, responds to changes in membrane composition induced by perturbation of endogenous lipid biosynthetic pathways or exogenous application of lipid. The primary substrates of Dnf2 are two chemically divergent lipids, glucosylceramide (GlcCer) and phosphatidylcholine ((PC) or their lyso-lipid derivatives), and we find that these substrates compete with each other for transport. Acutely inhibiting sphingolipid synthesis using myriocin attenuates transport of exogenously applied GlcCer without perturbing PC transport. Deletion of genes controlling later steps of glycosphingolipid production also perturb GlcCer transport to a greater extent than PC transport. Surprisingly, application of lipids that are poor transport substrates differentially affect PC and GlcCer transport by Dnf2, thus altering substrate preference. Our data indicate that Dnf2 exhibits exquisite sensitivity to the membrane composition; thus, providing feedback onto the function of the P4-ATPases.
Structural basis ofBlastomycesEndoglucanase-2 adjuvancy in anti-fungal and -viral immunity
Authors: Santos Dias Lucas Dos , Dobson Hannah E. , Bakke Brock Kingstad , Kujoth Greg C. , Huang Junfeng , Kohn Elaine M. , Taira Cleison Ledesma , Wang Huafeng , Supekar Nitin T. , Azadi Parastoo , Li Lingjun , Suresh M. , Klein Bruce S. , Wüthrich Marcel
Published: June 2020

The development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. Current vaccines against infectious diseases preferentially induce protective antibodies driven by adjuvants such as alum. However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy,Blastomycesendoglucanase-2 (Bl-Eng2). We also pinpoint the developmental steps of antigen-specific CD4+and CD8+T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit induced protective immunity against lethal influenza and fungal pulmonary challenge.

AUTHOR SUMMARY

Fungal disease remains a challenging clinical and public health problem in part because there is no commercial vaccine available. The lack of suitable adjuvants is a critical barrier to developing safe and effective vaccines against fungal pathogens. Current adjuvants such as alum preferentially induce antibody responses which may be limited in mediating protection against fungi. Clinical observations and animal studies implicate cellular immunity as the essential component for the resolution of fungal infections. We have recently discovered an adjuvant that augments cell mediated immune responses and vaccine induced protection against fungi. Here, we identified the structural and mechanistic requirements by which this newly discovered adjuvant induces cell mediated immunity against fungi. As a proof of principle we also demonstrate that the adjuvant drives cellular immune responses against viruses such as influenza. We anticipate that our adjuvant can be used for vaccination with safe subunit vaccines against many microbial pathogens including viruses, intracellular bacteria, fungi and parasites that require cell mediated immune responses.
Systems genetics analyses in Diversity Outbred mice inform human bone mineral density GWAS and identifyQsox1as a novel determinant of bone strength
Authors: Al-Barghouthi Basel M. , Mesner Larry D. , Calabrese Gina M. , Brooks Daniel , Tommasini Steven M. , Bouxsein Mary L. , Horowitz Mark C. , Rosen Clifford J. , Nguyen Kevin , Haddox Samuel , Farber Emily A. , Onengut-Gumuscu Suna , Pomp Daniel , Farber Charles R.
Published: June 2020

Genome-wide association studies (GWASs) for osteoporotic traits have identified over 1000 associations; however, their impact has been limited by the difficulties of causal gene identification and a strict focus on bone mineral density (BMD). Here, we used Diversity Outbred (DO) mice to directly address these limitations by performing the first systems genetics analysis of 55 complex skeletal phenotypes. We applied a network approach to cortical bone RNA-seq data to discover 72 genes likely to be causal for human BMD GWAS associations, including the novel genesSERTAD4andGLT8D2. We also performed GWAS in the DO for a wide-range of bone traits and identifiedQsox1as a novel gene influencing cortical bone accrual and bone strength. Our results provide a new perspective on the genetics of osteoporosis and highlight the ability of the mouse to inform human genetics.
Dopamine-related striatal neurophysiology is associated with specialization of frontostriatal reward circuitry through adolescence
Authors: Parr Ashley C. , Calabro Finnegan , Larsen Bart , Tervo-Clemmens Brenden , Foran Will , Olafsson Valur , Luna Beatriz
Published: June 2020

Characterizing developmental changes in frontostriatal circuitry is critical to our understanding of adolescent development and can clarify neurobiological mechanisms underlying increased reward sensitivity and sensation seeking, and the emergence of psychopathology during this period. However, the role of striatal neurobiology in the development of frontostriatal circuitry through human adolescence remains largely unknown. We combine longitudinal MR-based assessments of striatal tissue-iron as a correlate of dopamine-related neurobiology with functional magnetic resonance imaging indices of resting-state and reward-state connectivity to investigate the contribution of dopaminergic processes to developmental changes in frontostriatal circuitry. Connectivity between the nucleus accumbens and ventral anterior cingulate, subgenual cingulate, and orbitofrontal cortices decreased through adolescence into adulthood. Nucleus accumbens tissue-iron mediated age-related changes and was associated with variability in connectivity. Our results provide evidence that developmental changes in dopamine-related striatal properties contribute to specialization of frontostriatal circuitry, potentially underlying changes in sensation seeking and reward sensitivity into adulthood.
Impact Of Covid-19 Pandemic On Mental Health Of Medical Students: A Cross-Sectional Study Using GAD-7 And PHQ-9 Questionnaires
Authors: Sartorão Filho Carlos Izaias , de Las Villas Rodrigues Wilson Conte , de Castro Ricardo Beauchamp , Marçal Arlete Aparecida , Pavelqueires Shirlene , Takano Luiz , de Oliveira Wilson Luis , Sartorão Neto Carlos Izaias
Published: June 2020

Aim

to evaluate anxiety and depression disorders among medical students during COVID-19 pandemic.

Methods

cross-sectional study of medical students conducted in May 2020 with questionnaires regarding social and demographic status and GAD-7 for anxiety and PHQ-9 for depression questionnaires.

Results

participated 340 (97.98%) students. Average GAD-7 score was 9.18 (M = 9.18; SD = 4.75); average PHQ-9 score was 12.72 (M = 12.72; SD = 6.62). Results indicate a positive significant relationship between GAD-7 and females, and social distancing affecting finances. Using cut-off score of 10 for GAD-7, 157 (46.17%) students were identified with moderated or severe symptoms of anxiety. For PHQ-9 score, using cut-off of 10, 219 (64.41%) students were identified with moderate or severe symptoms of depression; results indicate a positive significant relationship between PHQ-9 and females and between social distancing affecting finances.

Conclusion

analysis demonstrated a higher prevalence of moderated and severe anxiety and depression symptoms among medical students during COVID-19 pandemic, significantly among women and on medical students relating financial impairment related to COVID-19 epidemic.

The project was approved by the Research Ethics Committee of Institution under report number CAAE: 30718220.5.0000.8547
Circuit mechanisms for chemical modulation of cortex-wide network interactions and exploration behavior
Authors: Pfeffer T. , Ponce-Alvarez A. , Meindertsma T. , Gahnström C. , van den Brink R. L. , Nolte G. , Tsetsos K. , Engel A.K. , Deco G. , Donner T.H.
Published: June 2020

Influential accounts postulate distinct roles of the catecholamine and acetylcholine neuromodulatory systems in cognition and behavior. But previous work found similar effects of these modulators on the response properties of individual cortical neurons. Here, we report a double dissociation between catecholamine and acetylcholine effects at the level of cortex-wide network interactions in humans. A pharmacological boost of catecholamine levels increased cortex-wide interactions during a visual task, but not rest. Conversely, an acetylcholine-boost decreased correlations during rest, but not task. Cortical circuit modeling explained this dissociation by differential changes in two circuit properties: the local excitation-inhibition balance (more strongly altered by catecholamines) and intracortical transmission (more strongly reduced by acetylcholine). The inferred catecholaminergic mechanism also predicted increased behavioral exploration, which we confirmed in human behavior during both a perceptual and value-based choice task. In sum, we identified specific circuit mechanisms for shaping cortex-wide network interactions and behavior by key neuromodulatory systems.
Induced DNA bending by unique dimerization of HigA antitoxin
Authors: Park Jin-Young , Kim Hyo Jung , Pathak Chinar , Yoon Hye-Jin , Kim Do-Hee , Park Sung Jean , Lee Bong-Jin
Published: June 2020

The bacterial toxin–antitoxin (TA) system regulates cell growth under various environmental stresses.Mycobacterium tuberculosis, the causative pathogen of tuberculosis (TB), has three HigBA type II TA systems with reverse gene organization, consisting of the toxin protein HigB and labile antitoxin protein HigA. Most type II TA modules are transcriptionally autoregulated by the antitoxin itself. In this report, we first present the crystal structure of theM. tuberculosisHigA3 antitoxin (MtHigA3) andMtHigA3 bound to its operator DNA complex. We also investigated the interaction betweenMtHigA3 and DNA using NMR spectroscopy. TheMtHigA3 antitoxin structure is a homodimer that contains a structurally well conserved DNA-binding domain at the N-terminus and a dimerization domain at the C-terminus. Upon comparing the HigA homologue structures, a distinct difference was found in the C-terminal region that possesses the β-lid, and diverse orientations of two helix–turn–helix (HTH) motifs from HigA homologue dimers were observed. The structure ofMtHigA3 bound to DNA reveals that the promoter DNA is bound to two HTH motifs of theMtHigA3 dimer presenting 46.5° bending, and the distance between the two HTH motifs of eachMtHigA3 monomer was increased inMtHigA3 bound to DNA. The β-lid, which is found only in the tertiary structure ofMtHigA3 among the HigA homologues, causes the formation of a tight dimerization network and leads to a unique arrangement for dimer formation that is related to the curvature of the bound DNA. This work could contribute to the understanding of the HigBA system ofM. tuberculosisat the atomic level and may contribute to the development of new antibiotics for TB treatment.
Millisecond time-resolved serial oscillation crystallography of a blue-light photoreceptor at a synchrotron
Authors: Aumonier Sylvain , Santoni Gianluca , Gotthard Guillaume , von Stetten David , Leonard Gordon A. , Royant Antoine
Published: June 2020

The recent development of serial crystallography has popularized time-resolved crystallography as a technique to determine the structure of protein-reaction intermediate states. However, most approaches rely on the availability of thousands to millions of microcrystals. A method is reported here, using monochromatic synchrotron radiation, for the room-temperature collection, processing and merging of X-ray oscillation diffraction data from <100 samples in order to observe the build up of a photoreaction intermediate species. Using this method, we monitored with a time resolution of 63 ms how the population of a blue-light photoreceptor domain in a crystal progressively photoconverts from the dark to the light state. The series of resulting snapshots allows us to visualize in detail the gradual rearrangement of both the protein and chromophore during this process.
On the drivers of profitability in the banking industry in restructuring times: a Bayesian perspective
Authors: Cruz-García Paula , Forte Anabel , Peiró-Palomino Jesús
Published: June 2020

Purpose

There is abundant literature analyzing the determinants of banks’ profitability through its main component: the net interest margin. Some of these determinants are suggested by seminal theoretical models and subsequent expansions. Others are ad-hoc selections. Up to now, there are no studies assessing these models from a Bayesian model uncertainty perspective. This paper aims to analyze this issue for the EU-15 countries for the period 2008-2014, which mainly corresponds to theGreat Recessionyears.

Design/methodology/approach

It follows a Bayesian variable selection approach to analyze, in a first step, which variables of those suggested by the literature are actually good predictors of banks’ net interest margin. In a second step, using a model selection approach, the authors select the model with the best fit. Finally, the paper provides inference and quantifies the economic impact of the variables selected as good candidates.

Findings

The results widely support the validity of the determinants proposed by the seminal models, with only minor discrepancies, reinforcing their capacity to explain net interest margin disparities also during the recent period of restructuring of the banking industry.

Originality/value

The paper is, to the best of the knowledge, the first one following a Bayesian variable selection approach in this field of the literature.
Experimental and numerical analysis on using CuO-Al2O3/water hybrid nanofluid in a U-type tubular heat exchanger
Authors: Gürbüz Emine Yağız , Variyenli Halil İbrahim , Sözen Adnan , Khanlari Ataollah , Ökten Mert
Published: June 2020

Purpose

Heat exchangers (HEXs) are extensively used in many applications such as heating and cooling systems. To increase the thermal performance of HEXs, nano-sized particles could be added to the base working fluid which can improve the thermophysical properties of the fluid. In addition, further improvement in the thermal performance of nanofluids can be obtained by using two or more different nanoparticles which are known as hybrid nanofluids. This paper aims to improve the thermal efficiency of U-type tubular HEX (THEX) by using CuO-Al2O3/water hybrid nanofluid.

Design/methodology/approach

Numerical simulation has been used to model THEX with various configurations. Also, CuO-Al2O3/water hybrid nanofluid has been experimented in THEX in two various modes including parallel (PTHEX) and counter flow (CTHEX) regarding to the numerical findings. Hybrid nanofluids have been prepared in two particle concentrations and compared with CuO/water nanofluid at the same concentrations and also with water.

Findings

The numerical simulation results showed that adding fins and also using hybrid nanofluid can increase heat transfer rate in HEX. However, adding fins cannot be a good option in U-type THEX with lower diameter because it increases pressure drop notably. Experimental results of this work illustrated that using Al2O3-CuO/water hybrid nanofluid in the THEX improved thermal performance significantly. Maximum enhancement in overall heat transfer coefficient of THEX by using CuO-Al2O3/water nanofluid in 0.5% and 1% concentrations achieved as 9.5% and 12%, respectively.

Originality/value

The obtained findings of the study showed the positive effects of using hybrid type nanofluid in comparison with single type nanofluid. In this study, numerical and experimental analysis have been conducted to investigate the effect of using hybrid type nanofluid in U-type HEX. The obtained results exhibited successful utilization of CuO-Al2O3/water hybrid type nanofluid in HEX. Moreover, it was observed that thermal performance analysis of the nanofluids without any experiment can be done by using numerical method.