bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional partnership between carbonic anhydrase and malic enzyme in promoting gluconeogenesis inLeishmania major
Authors: Mondal Dipon Kumar , Pal Dhiman Sankar , Abbasi Mazharul , Datta Rupak
Published: June 2020

Leishmaniahas a remarkable ability to proliferate under widely fluctuating levels of essential nutrients, such as glucose. For this the parasite is heavily dependent on its gluconeogenic machinery. One perplexing aspect of gluconeogenesis inLeishmaniais the lack of the crucial pyruvate carboxylase (PC) gene. PC-catalyzed conversion of pyruvate to oxaloacetate is a key entry point through which gluconeogenic amino acids are funnelled into this pathway. Absence of PC inLeishmaniathus raises question about the mechanism of pyruvate entry into the gluconeogenic route. We report here that this task is accomplished inLeishmania majorthrough a novel functional partnership between its mitochondrial malic enzyme (LmME) and cytosolic carbonic anhydrase (LmCA1). Using a combination of pharmacological inhibition studies with genetic manipulation, we showed that both these enzymes are necessary in promoting gluconeogenesis and supporting parasite growth under glucose limiting condition. Functional crosstalk between LmME and LmCA1 was evident when it was observed that the growth retardation caused by inhibition of any one of these enzymes could be protected to a significant extent by overexpressing the other enzyme. We also found that while LmCA1 exhibited constitutive expression, LmME protein level was strongly upregulated in low glucose condition. Notably, both LmME and LmCA1 were found to be important for survival ofLeishmaniaamastigotes within host macrophages. Taken together, our results indicate that LmCA1 by virtue of its CO2concentrating ability stimulates LmME-catalyzed pyruvate carboxylation, thereby driving gluconeogenesis through pyruvate-malate-oxaloacetate bypass pathway. Additionally, our study establishes LmCA1 and LmME as promising therapeutic targets.
Oscillatory correlates of auditory working memory examined with human electrocorticography
Authors: Kumar Sukhbinder , Gander Phillip E. , Berger Joel I. , Billig Alexander J. , Nourski Kirill V. , Oya Hiroyuki , Kawasaki Hiroto , Howard Matthew A. , Griffiths Timothy D.
Published: June 2020

This work examines how sounds are held in auditory working memory (AWM) in humans by examining oscillatory local field potentials (LFPs) in candidate brain regions. Previous fMRI studies by our group demonstrated blood oxygenation level-dependent (BOLD) response increases during maintenance in auditory cortex, inferior frontal cortex and the hippocampus using a paradigm with a delay period greater than 10s. The relationship between such BOLD changes and ensemble activity in different frequency bands is complex, and the long delay period raised the possibility that long-term memory mechanisms were engaged. Here we assessed LFPs in different frequency bands in six subjects with recordings from all candidate brain regions using a paradigm with a short delay period of 3 s. Sustained delay activity was demonstrated in all areas, with different patterns in the different areas. Enhancement in low frequency (delta) power and suppression across higher frequencies (beta/gamma) were demonstrated in primary auditory cortex in medial Heschl’s gyrus (HG) whilst non-primary cortex showed patterns of enhancement and suppression that altered at different levels of the auditory hierarchy from lateral HG to superior- and middle-temporal gyrus. Inferior frontal cortex showed increasing suppression with increasing frequency. The hippocampus and parahippocampal gyrus showed low frequency increases and high frequency decreases in oscillatory activity. The work demonstrates sustained activity patterns that can only be explained by AWM maintenance, with prominent low-frequency increases in medial temporal lobe regions.
The 20-hydroxyecdysone agonist, halofenozide, promotes anti-Plasmodiumimmunity inAnopheles gambiaevia the ecdysone receptor
Authors: Reynolds Rebekah A. , Kwon Hyeogsun , Alves e Silva Thiago Luiz , Olivas Janet , Vega-Rodriguez Joel , Smith Ryan C.
Published: June 2020

Mosquito physiology and immunity are integral determinants of malaria vector competence. This includes the principal role of hormonal signaling inAnopheles gambiaeinitiated shortly after blood-feeding, which stimulates immune induction and promotes vitellogenesis through the function of 20-hydroxyecdysone (20E). Previous studies demonstrated that manipulating 20E signaling through the direct injection of 20E or the application of a 20E agonist can significantly impactPlasmodiuminfection outcomes, reducing oocyst numbers and the potential for malaria transmission. In support of these findings, we demonstrate that a 20E agonist, halofenozide, is able to induce anti-Plasmodiumimmune responses that limitPlasmodiumookinetes. We demonstrate that halofenozide requires the function of ultraspiracle (USP), a component of the canonical heterodimeric ecdysone receptor, to induce malaria parasite killing responses. Additional experiments suggest that the effects of halofenozide treatment are temporal, such that its application only limits malaria parasites when applied prior to infection. Unlike 20E, halofenozide does not influence cellular immune function or AMP production. Together, our results further demonstrate the potential of targeting 20E signaling pathways to reduce malaria parasite infection in the mosquito vector and provide new insight into the mechanisms of halofenozide-mediated immune activation that differ from 20E.
Genetic dissection of Down syndrome-associated alterations in APP/amyloid-β biology using mouse models
Authors: Tosh Justin L. , Rhymes Ellie , Mumford Paige , Whittaker Heather T. , Pulford Laura J. , Noy Sue J. , Cleverley Karen , Walker Matthew C. , Tybulewicz Victor L.J. , Wykes Rob C. , Fisher Elizabeth M.C , Wiseman Frances K.
Published: June 2020

Individuals who have Down syndrome (caused by trisomy of chromosome 21), have a greatly elevated risk of early-onset Alzheimer’s disease, in which amyloid-β accumulates in the brain. Amyloid-β is a product of the chromosome 21 geneAPP(amyloid precursor protein) and the extra copy or ‘dose’ ofAPPis thought to be the cause of this early-onset Alzheimer’s disease. However, other chromosome 21 genes likely modulate disease when in three-copies in people with Down syndrome. Here we show that an extra copy of chromosome 21 genes, other thanAPP, influences APP/Aβ biology. We crossed Down syndrome mouse models with partial trisomies, to anAPPtransgenic model and found that extra copies of subgroups of chromosome 21 gene(s) modulate amyloid-β aggregation andAPPtransgene-associated mortality, independently of changing amyloid precursor protein abundance. Thus, genes on chromosome 21, other thanAPP, likely modulate Alzheimer’s disease in people who have Down syndrome.
Structural Diversity and Phylogenetic Distribution of Valyl tRNA-like Structures in Viruses
Authors: Sherlock Madeline E. , Hartwick Erik W. , MacFadden Andrea , Kieft Jeffrey S.
Published: June 2020

Viruses commonly use specifically folded RNA elements that interact with both host and viral proteins to perform functions important for diverse viral processes. Examples are found at the 3′ termini of certain positive-sense ssRNA virus genomes where they partially mimic tRNAs, including being aminoacylated by host cell enzymes. Valine-accepting tRNA-like structures (TLSVal) are an example that share some clear homology to canonical tRNAs but have several important structural differences. Although many examples of TLSValhave been identified, we lacked a full understanding of their structural diversity and phylogenetic distribution. To address this, we undertook an in-depth bioinformatic and biochemical investigation of these RNAs, guided by recent high-resolution structures of a TLSVal. We cataloged many new examples in plant-infecting viruses but also in unrelated insect-specific viruses. Using biochemical and structural approaches, we verified the secondary structure of representative TLSValsubstrates and tested their ability to be valylated, finding structural heterogeneity within this class. In a few cases, large stem-loop structures are inserted within distinct variable regions located in an area of the TLS distal to known host cell factor binding sites. In addition, we identified one virus whose TLS has switched its anticodon away from valine; the implications of this remain unclear. These results refine our understanding of the structural and functional mechanistic details of tRNA mimicry and how this may be used in viral infection.
On Linear Growth in COVID-19 Cases
Authors: Grinfeld Michael , Mulheran Paul A.
Published: June 2020

We present an elementary model of COVID-19 propagation that makes explicit the connection between testing strategies and rates of transmission and the linear growth in new cases observed in many parts of the world. An essential feature of the model is that it captures the population-level response to the infection statistics information provided by governments and other organisations. The conclusions from this model have important implications regarding benefits of wide-spread testing for the presence of the virus, something that deserves greater attention.
POLArIS, a versatile probe for molecular orientation, revealed actin filaments associated with microtubule asters in early embryos
Authors: Sugizaki Ayana , Sato Keisuke , Chiba Kazuyoshi , Saito Kenta , Kawagishi Masahiko , Tomabechi Yuri , Mehta Shalin B. , Ishii Hirokazu , Sakai Naoki , Shirouzu Mikako , Tani Tomomi , Terada Sumio
Published: June 2020

Biomolecular assemblies govern the physiology of cells. Their function often depends on the changes in molecular arrangements of constituents, both in the positions and orientations. While recent advancements of fluorescence microscopy including super-resolution microscopy have enabled us to determine the positions of fluorophores with unprecedented accuracy, monitoring orientation of fluorescently labeled molecules within living cells in real-time is challenging. Fluorescence polarization microscopy (FPM) reports the orientation of emission dipoles and is therefore a promising solution. For imaging with FPM, target proteins need labeling with fluorescent probes in a sterically constrained manner, but due to difficulties in the rational three-dimensional design of protein connection, universal method for constrained tagging with fluorophore was not available. Here we report POLArIS, a genetically encoded and versatile probe for molecular orientation imaging. Instead of using a direct tagging approach, we used a recombinant binder connected to a fluorescent protein in a sterically constrained manner and can target arbitrary biomolecules by combining with phage-display screening. As an initial test case of POLArIS, we developed POLArISact, which specifically binds to F-actin in living cells. We confirmed that the orientation of F-actin can be monitored by observing cells expressing POLArISactwith FPM. In living starfish early embryos expressing POLArISact, we found actin filaments radially extending from centrosomes in association with microtubule asters during mitosis. By taking advantage of the genetically encoded nature, POLArIS can be used in a variety of living specimens including whole bodies of developing embryos and animals, and also expressed in a cell-type/tissue specific manner.
SARS-CoV-2 infection of African green monkeys results in mild respiratory disease discernible by PET/CT imaging and prolonged shedding of infectious virus from both respiratory and gastrointestinal tracts
Authors: Hartman Amy L. , Nambulli Sham , McMillen Cynthia M. , White Alexander G. , Tilston-Lunel Natasha L. , Albe Joseph R. , Cottle Emily , Dunn Matthew , Frye L. James , Gilliland Theron H. , Olsen Emily L. , O’Malley Katherine J. , Schwarz Madeline M. , Tomko Jaime A. , Walker Reagan C. , Xia Mengying , Hartman Matthew S. , Klein Edwin , Scanga Charles A. , Flynn JoAnne L. , Klimstra William B. , McElroy Anita K. , Reed Douglas S. , Duprex W. Paul
Published: June 2020

Vaccines are urgently needed to combat the global coronavirus disease 2019 (COVID-19) pandemic, and testing of candidate vaccines in an appropriate non-human primate (NHP) model is a critical step in the process. Infection of African green monkeys (AGM) with a low passage human isolate of SARS-CoV-2 by aerosol or mucosal exposure resulted in mild clinical infection with a transient decrease in lung tidal volume. Imaging with human clinical-grade18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) co-registered with computed tomography (CT) revealed pulmonary lesions at 4 days post-infection (dpi) that resolved over time. Infectious virus was shed from both respiratory and gastrointestinal (GI) tracts in all animals in a biphasic manner, first between 2-7 dpi followed by a recrudescence at 14-21 dpi. Viral RNA (vRNA) was found throughout both respiratory and gastrointestinal systems at necropsy with higher levels of vRNA found within the GI tract tissues. All animals seroconverted simultaneously for IgM and IgG, which has also been documented in human COVID-19 cases. Young AGM represent an excellent species to study mild/subclinical COVID-19 disease and have shed light on unknown aspects of long-term virus shedding. They are ideally suited for preclinical evaluation of candidate vaccines and therapeutic interventions.

One Sentence Summary

Subclinical infection of African green monkeys infected with SARS-CoV-2 results in prolonged shedding of infectious virus from both respiratory and gastrointestinal tracts.
Structural templates for imaging EEG cortical sources in infants
Authors: O’Reilly Christian , Larson Eric , Richards John E. , Elsabbagh Mayada
Published: June 2020

Electroencephalographic (EEG) source reconstruction is a powerful approach that helps to unmix scalp signals, mitigates volume conduction issues, and allows anatomical localization of brain activity. Algorithms used to estimate cortical sources require an anatomical model of the head and the brain, generally reconstructed using magnetic resonance imaging (MRI). When such scans are unavailable, a population average can be used for adults, but no average surface template is available for cortical source imaging in infants. To address this issue, this paper introduces a new series of 12 anatomical models for subjects between zero and 24 months of age. These templates are built from MRI averages and volumetric boundary element method segmentation of head tissues available as part of the Neurodevelopmental MRI Database. Surfaces separating the pia mater, the gray matter, and the white matter were estimated using the Infant FreeSurfer pipeline. The surface of the skin as well as the outer and inner skull surfaces were extracted using a cube marching algorithm followed by Laplacian smoothing and mesh decimation. We post-processed these meshes to correct topological errors and ensure watertight meshes. The use of these templates for source reconstruction is demonstrated and validated using 100 high-density EEG recordings in 7-month-old infants. Hopefully, these templates will support future studies based on EEG source reconstruction and functional connectivity in healthy infants as well as in clinical pediatric populations. Particularly, they should make EEG-based neuroimaging more feasible in longitudinal neurodevelopmental studies where it may not be possible to scan infants at multiple time points.

Graphical abstract

Highlights

Twelve surface templates for infants in the 0-2 years old range are proposed

These templates can be used for EEG source reconstruction using existing toolboxes

A relatively modest impact of age differences was found in this age range

Correlation analysis confirms increasing source differences with age differences

Sources reconstructed with infants versus adult templates significantly differ
Bacterial retrons function in anti-phage defense
Authors: Millman Adi , Bernheim Aude , Stokar-Avihail Avigail , Fedorenko Taya , Voichek Maya , Leavitt Azita , Sorek Rotem
Published: June 2020

Retrons are bacterial genetic elements comprised of a reverse transcriptase (RT) and a non-coding RNA. The RT uses the non-coding RNA as a template, generating a chimeric RNA/DNA molecule in which the RNA and DNA components are covalently linked. Although retrons were discovered three decades ago, their function remained unknown. In this study we report that retrons function as anti-phage defense systems. The defensive unit is composed of three components: the RT, the non-coding RNA, and an effector protein. Retron-containing systems are abundant in genomic “defense islands”, suggesting a role for most retrons in phage resistance. By cloning multiple retron systems into a retron-lessEscherichia colistrain, we show that these systems confer defense against a broad range of phages, with different retrons defending against different phages. Focusing on a single retron, Ec48, we show evidence that it is a “guardian” of RecBCD, a complex with central anti-phage functions in the bacterial cell. Inhibition of RecBCD by dedicated phage proteins activates the retron, leading to abortive infection and cell death. Thus, the Ec48 retron forms a second line of defense that is triggered if the first lines of defense have collapsed. Our results expose a new family of anti-phage defense systems abundant in bacteria.
Delineating single subject oscillatory brain networks with Spatio-Spectral Eigenmodes
Authors: Quinn Andrew J , Green Gary GR , Hymers Mark
Published: June 2020

The spatial and spectral structure of oscillatory networks in the brain provide a readout of the underlying neuronal function. Within and between subject variability in these networks can be highly informative but also poses a considerable analytic challenge. Here, we describe a method that simultaneously estimate spectral and spatial network structure without assumptions about either feature distorting estimation of the other. This enables analyses exploring how variability in the frequency and spatial structure of oscillatory networks might vary both across the brain and across individuals. The method performs a modal decomposition of an autoregressive model to describe the oscillatory signals present within a time-series based on their peak frequency and damping time. Moreover, an alternate mathematical formulation for the system transfer function can be written in terms of these oscillatory modes; describing the spatial topography and network structure of each component. We define a set of Spatio-Spectral Eigenmodes (SSEs) from these parameters to provide a parsimonious description of oscillatory networks. Crucially, the SSEs preserve the rich between-subject variability and are constructed without pre-averaging within specified frequency bands or limiting analyses to single channels or regions. After validating the method on simulated data, we explore the structure of whole brain oscillatory networks in eyes-open resting state MEG data from the Human Connectome Project. We are able to show a wide variability in peak frequency and network structure of alpha oscillations and reveal a distinction between occipital ‘high-frequency alpha’ and parietal ‘low-frequency alpha’. The frequency difference between occipital and parietal alpha components is present within individual participants but is partially masked by larger between subject variability; a 10Hz oscillation may represent the high-frequency occipital component in one participant and the low-frequency parietal component in another. This rich characterisation of individual neural phenotypes has the potential to enhance analyses into the relationship between neural dynamics and a person’s behavioural, cognitive or clinical state
Patients with ventromedial prefrontal lesions show an implicit approach bias to angry faces
Authors: Buades-Rotger Macià , Solbakk Anne-Kristin , Liebrand Matthias , Endestad Tor , Funderud Ingrid , Siegwardt Paul , Enter Dorien , Roelofs Karin , Krämer Ulrike M.
Published: June 2020

Damage to the ventromedial prefrontal cortex (VMPFC) can cause maladaptive social behavior, but the cognitive processes underlying these behavioral changes are still uncertain. Here, we tested whether patients with acquired VMPFC lesions show altered approach-avoidance tendencies to emotional facial expressions. Thirteen patients with focal VMPFC lesions and 31 age- and gender-matched healthy controls performed an implicit approach-avoidance task in which they either pushed or pulled a joystick depending on stimulus color. While controls avoided angry faces, VMPFC patients displayed an incongruent response pattern characterized by both increased approach and reduced avoidance of angry facial expressions. The approach bias was stronger in patients with higher self-reported impulsivity and disinhibition, and in those with larger lesions. We further used linear ballistic accumulator modelling to investigate latent parameters underlying approach-avoidance decisions. Controls displayed negative drift rates when approaching angry faces, whereas VMPFC lesions abolished this pattern. In addition, VMPFC patients had weaker response drifts than controls during avoidance. Finally, patients showed reduced drift rate variability and shorter non-decision times, indicating impulsive and rigid decision-making. Our findings thus suggest that VMPFC damage alters the pace of evidence accumulation in response to social signals, eliminating a default, protective avoidant bias and facilitating dysfunctional approach behavior.
Pangenome of white lupin provides insights into the diversity of the species
Authors: Hufnagel Bárbara , Soriano Alexandre , Taylor Jemma , Divol Fanchon , Kroc Magdalena , Sanders Heather , Yeheyis Likawent , Nelson Matthew , Péret Benjamin
Published: June 2020

Background

White lupin is an old crop with renewed interest due to its seed high protein content and high nutritional value. Despite a long domestication history in the Mediterranean basin, modern breeding efforts have been fairly scarce. Recent sequencing of its genome has provided tools for further description of genetic resources but detailed characterization is still missing.

Results

Here, we report the genome sequencing of several accessions that were used to establish a white lupin pangenome. We defined core genes that are present in all individuals and variable genes that are absent in some and may represent a gene pool for stress adaptation. We believe that the identification of novel genes, together with a more comprehensive reference sequence, represents a significant improvement of the white lupin genetic resources. As an example, we used this pangenome to identify selection footprints and to provide a candidate gene for one of the main QTLs associated with late flowering in Ethiopian lupin types. A 686 nucleotide deletion was identified in exon 3 of theLaFTa1(Lupinus albus Flowering Time a1) gene that suggests a molecular origin for this trait of importance, defining the need for vernalization in some lupins.

Conclusions

The white lupin pangenome provides a novel genetic resource to better understand how domestication has shaped the genomic variability amongst this crop. It will be of major importance for breeders to select new breeding traits and incorporate them into new, more efficient and robust cultivars in order to face a growing demand for plant protein sources, notably in Europe.
Rate volatility and asymmetric segregation diversify mutation burden in mutator cells
Authors: Dowsett I.T. , Sneeden J. , Olson B.J. , McKay-Fleisch J. , McAuley E. , Kennedy S.R. , Herr A.J.
Published: June 2020

Mutations that compromise mismatch repair (MMR) or DNA polymerase exonuclease domains produce mutator phenotypes capable of fueling cancer evolution. Tandem defects in these pathways dramatically increase mutation rate. Here, we model how mutator phenotypes expand genetic heterogeneity in budding yeast cells using a single-cell resolution approach that tallies all replication errors arising from individual divisions. The distribution of count data from cells lacking MMR and polymerase proofreading was broader than expected for a single rate, consistent with volatility of the mutator phenotype. The number of mismatches that segregated to the mother and daughter cells after the initial round of replication co-varied, suggesting that mutagenesis in each division is governed by a different underlying rate. The distribution of “fixed” mutation counts that cells inherit is further broadened by an unequal sharing of mutations due to semiconservative replication and Mendelian segregation. Modeling suggests that this asymmetric segregation may diversify mutation burden in mutator-driven tumors.
Evidence Accumulation Modelling Reveals that Gaussian Noise Accounts for Inhibition of Return
Authors: Malkinson Tal Seidel , Bourgeois Alexia , Wattiez Nicolas , Pouget Pierre , Bartolomeo Paolo
Published: June 2020

Inhibition of return (IOR) refers to the slowing of response times (RTs) for stimuli repeated at previously inspected locations, as compared with novel ones. However, the exact processing stage(s) at which IOR occurs, and its nature across different response modalities, remain debated. We tested predictions on these issues originating from the FORTIOR model (fronto-parietal organization of response times in IOR; Seidel Malkinson & Bartolomeo, 2018), and from evidence accumulation models. We reanalysed RT data from a target-target IOR paradigm (Bourgeois et al.,2013a, 2013b) by using a LATER-like evidence accumulation model (Carpenter & Williams, 1995), to test the predictions of FORTIOR, and specifically whether IOR could occur at sensory/attentional stages of processing, or at stages of decision and action selection. We considered the following conditions: manual or saccadic response modality, before or after TMS perturbation over four cortical regions. Results showed that the Gaussian noise parameter best explained both manual and saccadic IOR, suggesting that in both response modalities IOR may result from slower accumulation of evidence for repeated locations. Additionally, across stimulated regions, TMS affected only manual RTs, lowering them equally in the conditions with repeated targets (Return) and non-repeated targets (Non-return). Accordingly, the modelling results show that TMS stimulation did not significantly alter the pattern between model parameters, with the Gaussian noise parameter remaining the parameter best explaining the Return - Non-return RT difference. Moreover, TMS over the right intra-parietal sulcus (IPS) perturbed IOR by shortening the Return RT. When directly testing this effect by modelling the TMS impact in the Return condition, the Bayesian information criterion of the Gaussian noise parameter was the smallest, but this effect did not reach significance. These results support the hypothesis that target-target IOR is a predominantly sensory/attentional phenomenon, and may be modulated by activity in fronto-parietal networks.
COGENT: evaluating the consistency of gene co-expression networks
Authors: Bozhilova Lyuba V. , Pardo-Diaz Javier , Reinert Gesine , Deane Charlotte M.
Published: June 2020

Gene co-expression networks can be constructed in multiple different ways, both in the use of different measures of co-expression, and in the thresholds applied to the calculated co-expression values, from any given dataset. It is often not clear which co-expression network construction method should be preferred. COGENT provides a set of tools designed to aid the choice of network construction method without the need for any external validation data.

Availability and implementation

https://github.com/lbozhilova/COGENT
Robust gene coexpression networks using signed distance correlation
Authors: Pardo-Diaz Javier , Bozhilova Lyuba V. , Beguerisse-Díaz Mariano , Poole Philip S. , Deane Charlotte M. , Reinert Gesine
Published: June 2020

Motivation

Even within well studied organisms, many genes lack useful functional annotations. One way to generate such functional information is to infer biological relationships between genes/proteins, using a network of gene coexpression data that includes functional annotations. However, the lack of trustworthy functional annotations can impede the validation of such networks. Hence, there is a need for a principled method to construct gene coexpression networks that capture biological information and are structurally stable even in the absence of functional information.

Results

We introduce the concept of signed distance correlation as a measure of dependency between two variables, and apply it to generate gene coexpression networks. Distance correlation offers a more intuitive approach to network construction than commonly used methods such as Pearson correlation. We propose a framework to generate self-consistent networks using signed distance correlation purely from gene expression data, with no additional information. We analyse data from three different organisms to illustrate how networks generated with our method are more stable and capture more biological information compared to networks obtained from Pearson or Spearman correlations.

Code availability

https://github.com/javier-pardodiaz/sdcorGCN.
In situcharacterization of calcium fluxes in astrocytic mitochondria from the mouse striatum and hippocampus
Authors: Huntington Taylor E. , Srinivasan Rahul
Published: June 2020

Astrocytes govern critical aspects of brain function via Ca2+signals, the majority of which associate with mitochondria. However, little is known with regard toin situsources, kinetics or mechanisms of Ca2+influx in astrocytic mitochondria. To address this knowledge gap, we expressed the genetically encoded calcium indicator, GCaMP6f within the mitochondrial matrix of adult mouse astrocytes in the dorsolateral striatum (DLS) and hippocampus (HPC). We found spontaneous Ca2+events in astrocytic mitochondria with subcellular differences between somatic, branch, and branchlet mitochondria, as well as inter-regional differences between astrocytes in the DLS and HPC. We also found a strong dependency of spontaneous mitochondrial Ca2+fluxes on endoplasmic reticulum stores, the surprising lack of a major role for the mitochondrial calcium uniporter, MCU, and dual mitochondrial Ca2+responses with multiple neurotransmitter agonists. Together, our findings provide a foundational understanding of mechanisms for Ca2+influx in astrocytic mitochondria within disease-relevant brain regions.
Estimation of fatality rate in Africa through the behavior of COVID-19 in Italy relevance to age profiles
Authors: Nzungize Lambert , Umuhoza Diane , Dai Yongdong , Nzaou Stech A E. , Asaad Mohammed , Abokadoum M. A. , Ekomi Moure Ulrich Aymard , Xie Jianping
Published: June 2020

The emergence and pandemic of COVID-19 has rapidly become a global concern. In Italy, on 27 March 2020, there were 8165 deaths and 80539 confirmed cases of COVID-19. Demographic situations, like age profiles is reported to be the cause of high case fatality rate (CFR) in Italy. In Africa, the COVID-19 pandemic has not yet grasped epic proportion, but the estimation of CFR is still needed. We compared the CFR observed in Italy with the age profiles in 46 Africa countries and 2 territories which are already confirmed COVID-19 case. The estimation of the CFR in Africa ranges between (1.0%-5.4%) while in Italy is 10.1%. The five highest CFR countries and territories in Africa are Reunion (5.4%), Mauritius (5.1%), Tunisia (3.9%), Seychelles (3.8%) and Morocco (3.3%). The last three countries with low CFR are Uganda (1.0%), Zambia (1.1%) and Angola (1.1%). The observed difference is related to the age profiles.
Phage proteins block and trigger retron toxin/antitoxin systems
Authors: Bobonis Jacob , Mitosch Karin , Mateus André , Kritikos George , Elfenbein Johanna R. , Savitski Mikhail M. , Andrews-Polymenis Helene , Typas Athanasios
Published: June 2020

Bacteria carry dozens of Toxin/Antitoxin systems (TAs) in their chromosomes. Upon growth, the antitoxin is co-expressed and neutralizes the toxin. TAs can be activated and inhibit growth, but when and how this occurs has largely remained enigmatic, hindering our understanding of their physiological roles. We developed TIC/TAC (Toxin Inhibition/Activation Conjugation), a high-throughput reverse genetics approach, to systematically identify molecular blockers and triggers of TAs. By applying TIC/TAC to a tripartite TA, the retron-Sen2 ofSalmonellaTyphimurium, we have identified multiple blockers and triggers of phage origin. We demonstrate that diverse phage functionalities are sensed by the DNA-part of the antitoxin and ultimately activate the retron toxin. Phage-origin proteins can circumvent activation by directly blocking the toxin. Some identified triggers and blockers also act on anE. coliretron-TA, Eco9. We propose that retron-TAs act as abortive-infection anti-phage defense systems, and delineate mechanistic principles by which phages trigger or block them.
Heterogeneity of intrinsic excitability in Purkinje cells linked with longitudinal zebrin zones in the mouse cerebellum
Authors: Nguyen-Minh Viet T. , Tran-Anh Khoa , Sugihara Izumi
Published: June 2020

Heterogeneous populations of Purkinje cells (PCs), classified into zebrin-positive (Z+) and – negative (Z−) types, are arranged into separate longitudinal zones and are involved in different types of cerebellar learning. However, the electrophysiological phenotype that is brought about by the zebrin expression has not been much clarified in PCs. We compared electrophysiological characteristics in the soma and parallel fiber (PF)-PC synapse in Z+ and Z− PCs located in identified vermal and hemispheric zones in cerebellar slices in zebrin-reporter mice. Intrinsic excitability, intrinsic plasticity and PF-PC synaptic long term potentiation (LTP) occurred more strongly in Z− Purkinje cells than in Z+ PCs. The enhanced intrinsic plasticity was correlated with the reduction of medium-time-course after-hyperpolarization (mAHP) only in Z− PCs. These differences, which seem to be produced by the zebrin-linked expression of other functional molecules, may tune Z+ and Z− PCs to zone-specific cerebellar functions.
Resistance to the antifungal activity of Aprotinin occurs through mutations in genes that function in cation homeostasis
Authors: McColl Amanda I. , Lowe Rohan G.T. , McKenna James A. , Anderson Marilyn A. , Bleackley Mark R.
Published: June 2020

An increase in the prevalence of fungal infections is coinciding with an increase of resistance to current clinical antifungals, placing pressure on the discovery of new antifungal candidates. One option is to investigate drugs that have been approved for use for other medical conditions that have secondary antifungal activity. Aprotinin, also known as Bovine Pancreatic Trypsin inhibitor (BPTI), is an antifibrinolytic that has been approved for systemic use in patients in some countries. Bleackley and coworkers (2014) revealed that BPTI also has antifungal activity againstS. cerevisiaeandC. albicansand does this by targeting the magnesium transporterALR1.Here we have further investigated the potential for aprotinin to be used as an antifungal by assessing the development of resistance. We used anin vitromodel to assess the evolution of BPTI resistance/tolerance whereby BPTI was serial passaged with the model organismS. cerevisiae.Resistance to BPTI developed more quickly than resistance to the plant defensin NaD1 and the clinical antifungal, caspofungin. Full genome sequencing of resistant lines revealed that resistance to BPTI developed as the result of a deleterious mutation in either theptk2orsky1genes. This revealed that cation homeostasis and transport functions were particularly affected inS. cerevisiaeafter exposure to BPTI. Therefore, the mutations in these genes probably decreases release of magnesium and other cations from the cell, protecting the yeast from the limiting intracellular magnesium levels that arise when BPTI blocks the magnesium transporter Alr1p.
Theorizing parental intervention and young adults' career development: a social influence perspective
Authors: Liu Yan , Mao Yina , Wong Chi-Sum
Published: June 2020

Purpose

Drawing on the social influence literature and proposing parental intervention as a social influence process, this study seeks to theorize why parental intervention occurs and how it affects young adults' career development.

Design/methodology/approach

This paper adopts a conceptual design, offering a conceptual model based on social influence research and career development research.

Findings

It is proposed that parental intervention is a result of incongruence between parental expectations and young adults' interested occupations and between parents' assessments of young adults' qualities and job demands. Parents' traditionality moderates these relationships, while the success of parental intervention depends on young adults' traditionality and career maturity. Parents' position, referent and expert powers affect young adults' compliance, identification and internalization, respectively, which impact their occupational commitment and career satisfaction.

Research limitations/implications

Looking at parental intervention over time would help researchers understand this phenomenon more comprehensively than focusing only on its short-term effects as identified in the literature. The motivational processes of parental intervention triggered by power bases play a key role in determining young adults' long-term career consequences.

Practical implications

Career advisors should consider parents as a source of potential intervention in young adults' career choice. They may also provide parent-oriented services in addition to young adult-oriented services.

Originality/value

This framework contributes to the career development literature by adopting social influence approach to explain parental intervention in young adults' career choice and also providing implications for career counselors.
Readiness to franchise a teaching and examination event: the evolving case of the annual MUBS hospitality day
Authors: Mutumba Abbey
Published: June 2020

Learning outcomes

After reading and discussing this short case, the instructor should do the following: to enable the students to select and evaluate the main strength (sustainable competitive advantage) of an evolving brand whose leading manager needs to appreciate how it can be used to achieve the strategic objective of franchising it despite its challenges; to guide the students in choosing the most appropriate brand name that will sustainably reflect the parent organization’s identity and also retain its growing attractiveness to more event sponsors and other key partners in an environment of conflicting interests; to facilitate the students in choosing the appropriate strategy for strengthening the readiness to franchise and adapt a similar teaching and examining (annual event’s) model in a related course unit from among any of the target audience’s master and bachelor degree at another university elsewhere.

Case overview/synopsis

This short case shows how the annual Makerere University Business School (MUBS) hospitality day has evolved into a potential event franchise, which is attracting more VIPs, the media and demand to also be held in the country’s Vision 2040 cities where the respective campuses are located.

Complexity academic level

Bachelor (BA, BBA, BSc) and MBA/master degree level.

Supplementary materials

Teaching Notes are available for educators only.

Subject code

CSS 12: Tourism and hospitality.
Stress mindset and the work–family interface
Authors: Hammond Michelle M. , Murphy Caroline , Demsky Caitlin A.
Published: June 2020

Purpose

The current study aims to examine stress mindset as a moderator of the relationship between the work–family interface – work–family conflict (WFC) and enrichment (WFE) – and two work outcomes: job satisfaction and turnover intentions.

Design/methodology/approach

To examine these relationships, a cross-sectional online survey was conducted in Ireland (N = 314). Bootstrapping in SPSS was used to test the proposed hypotheses.

Findings

In addition to direct relationships between WFC/WFE and job satisfaction and turnover intentions, analyses showed that stress mindset is a moderator of the relationships between WFC and job satisfaction and turnover intentions, as well as of the relationship between WFE and job satisfaction, but not WFE and turnover intentions.

Research limitations/implications

Providing general support of the propositions of the conservation of resources theory, stress mindset was found to act as a personal resource affecting the relationships between WFC/WFE and most outcomes. The study findings indicate a need to further examine stress mindset in relation to employees' work and family interface.

Practical implications

In line with other research, this study recommends organizational efforts to reduce WFC and increase WFE. Further, as stress mindsets can be altered, practitioners may consider implementing stress mindset training to encourage employees' view of stress as enhancing rather than debilitating to reduce the negative impact of stress on employees in the workplace.

Social implications

Beliefs about the enhancing aspects of stress may allow employees to more effectively navigate transitions between work and family domains and maximize beneficial aspects of participating in both work and family roles.

Originality/value

This is the first paper to investigate the role of stress mindset as a moderator of the associations between the work–family interface and employee work-related outcomes. The findings are relevant to work–family researchers, managers and human resource professionals.
Outsourcing in humanitarian logistics – status quo and future directions
Authors: Gossler Timo , Wakolbinger Tina , Burkart Christian
Published: June 2020

Purpose

Outsourcing of logistics has great importance in disaster relief. Aid agencies spend several billion US dollars every year on logistics services. However, the concept of outsourcing has not been established adequately in literature on humanitarian logistics, leading to a fragmented view of the practice. This paper provides a holistic perspective of the concept by constructing a conceptual framework to analyze both practice and research of outsourcing in humanitarian operations. Based on this analysis, we explore future trends and identify research gaps.

Design/methodology/approach

The paper is based on a structured review of academic literature, a two-round Delphi study with 31 experts from aid agencies and a complementary full-day focus group with twelve experts from aid agencies and logistics service providers.

Findings

The paper systemizes the current practice of outsourcing in humanitarian logistics according to a conceptual framework of five dimensions: subject, object, partner, design and context. In addition, it reveals ten probable developments of the practice over the next years. Finally, it describes eight important research gaps and presents a research agenda for the field.

Research limitations/implications

The literature review considered peer-reviewed academic papers. Practitioner papers could provide additional insights into the practice. Moreover, the Delphi study focused on the perspective of aid agencies. Capturing the views of logistics service providers in more detail would be a valuable addition.

Originality/value

The paper establishes the academic basis for the important practice of outsourcing in humanitarian logistics. It highlights essential research gaps and, thereby, opens up the field for future research.
When method fails: walking as an alt-meth in a volatile context
Authors: Griffin Gabriele
Published: June 2020

Purpose

The purpose of this paper is to explore why the use of a particular qualitative method, walking, failed in a given context, the Chile of contemporary unrest.

Design/methodology/approach

The paper explores walking methodologies from a critical cultural perspective.

Findings

The article argues that context as socio-material entanglement, or people's relation to place, in a volatile situation, requires strong participatory engagement to enable productive outcomes and also that one can learn from the failure to generate such engagement.

Practical implications

The article suggests that enhanced participant involvement in experimental design (here a walking event) is necessary when the situation on the ground is conflict-ridden. It also suggests that explicitly articulating one's outsider position may facilitate productive exchanges in volatile contexts. The article further suggests that failure of method is a neglected but useful topic in qualitative research.

Social implications

Although walking methodologies frequently claim to be participant-centered, they are not always organized in that manner. If they are not, they risk undermining the democratic potential of alt-meths that is of particular importance in volatile contexts.

Originality/value

Failure of method is rarely reported on. The paper addresses that knowledge gap.
Paperwork, patronage, and citizenship: the materiality of everyday interactions with bureaucracy in Tamil Nadu, India
Authors: Carswell Grace , De Neve Geert
Published: June 2020

This article explores the material practices through which lower‐caste and poor villagers engage with bureaucracy in contemporary India. We take documents and paperwork – such as ration cards and community certificates – as a ‘lens’ through which to explore how paper materiality is infused with the politics of power, patronage, and identity. The article brings ethnography from rural Tamil Nadu, South India, in conversation with two bodies of literature: one on the materiality of bureaucracy and one on the nature of political mediation in contemporary India. We demonstrate how everyday engagements with paperwork as well as processes of applying, form filling, and securing recommendations are constitutive of social and political relationships and, ultimately, of citizenship itself. Political mediation around paperwork and bureaucracy generates a hierarchy of citizens rather than equal citizenship for all, yet ordinary villagers transpire as anything but passive. Drawing on patronage networks, engaging in affective performances, and navigating a politics of identity, they actively negotiate access to the state in an attempt to claim their rights as citizens.
Distant surgical teaching during COVID‐19 ‐ A pilot study on final year medical students
Authors: Co Michael , Chu Kent‐Man
Published: June 2020

Introduction

Due to the COVID‐19 outbreak, all on‐site undergraduate medical teaching activities in Hong Kong have been suspended. A new web‐based surgical skills learning (WSSL) for basic surgical skills training that were normally taught face‐to‐face was developed.

Methodology

Basic surgical skills were taught with normal face‐to‐face tutorial to 30 final year medical students prior to the outbreak. The same group of students were invited to join the online WSSL using Zoom. Evaluation of WSSL was performed by a standardized questionnaire.

Results

Thirty final year medical students (16 female, 14 male students) were recruited into the study. Median age was 23 (range 22‐24). Most of them believed that WSSL is easy to follow. When compared to face‐to‐face teaching. Most students (N = 22, 73.4%) felt that WSSL was just as difficult/easy as conventional teaching for learning instrumental knots. Students were asked to evaluate WSSL by using a Likert scale of 1 to 10 (with 10 being highly recommended). Twelve (40%) students highly recommended WSSL (Score 9 to 10), 15 students (50%) slightly recommended WSSL (Score 6‐8).

Conclusion

Web‐based surgical skills learning is a feasible alternative for face‐to‐face surgical skills teaching.