bluuebunny/crossref_metadata_2025 huggingface dataset:
Anatomy of unfolding: The site-specific fold stability of Yfh1 measured by 2D NMR
Authors: Puglisi Rita , Karunanithy Gogulan , Hansen D. Flemming , Pastore Annalisa , Temussi Piero Andrea
Published: March 2021

Most techniques allow detection of protein unfolding either by following the behaviour of single reporters or as an averaged all-or-none process. We recently added 2D NMR spectroscopy to the well-established techniques able to obtain information on the process of unfolding using resonances of residues in the hydrophobic core of a protein. Here, we questioned whether an analysis of the individual stability curves from each resonance could provide additional site-specific information. We used the Yfh1 protein that has the unique feature to undergo both cold and heat denaturation at temperatures above water freezing at low ionic strength. We show that stability curves inconsistent with the average NMR curve from hydrophobic core residues mainly comprise exposed outliers that do nevertheless provide precious information. By monitoring both cold and heat denaturation of individual residues we gain knowledge on the process of cold denaturation and convincingly demonstrate that the two unfolding processes are intrinsically different.
A machine-learning algorithm correctly classifies cortical evoked potentials from both natural retinal stimulation and electrical stimulation of the optic nerve
Authors: Gaillet Vivien , Zollinger Elodie Geneviève , Ghezzi Diego
Published: March 2021

Objective

Optic nerve’s intraneural stimulation is an emerging neuroprosthetic approach to provide artificial vision to totally blind patients. An open question is the possibility to evoke individual non-overlapping phosphenes via selective intraneural optic nerve stimulation. To begin answering this question, first, we aim at showing in preclinical experiments with animals that each intraneural electrode could evoke a distinguishable activity pattern in the primary visual cortex.

Approach

We performed both patterned visual stimulation and patterned electrical stimulation in healthy rabbits while recording evoked cortical activity with an electrocorticogram array in the primary visual cortex. Electrical stimulation was delivered to the optic nerve with the intraneural array OpticSELINE. We used a support vector machine algorithm paired to a linear regression model to classify cortical responses originating from visual stimuli located in different portions of the visual field and electrical stimuli from the different electrodes of the OpticSELINE.

Main results

Cortical activity induced by visual and electrical stimulation could be classified with nearly 100% accuracy relative to the specific location in the visual field or electrode in the array from which it originated. For visual stimulation, the accuracy increased with the separation of the stimuli and reached 100% for separation higher than 7 degrees. For electrical stimulation, at low current amplitudes, the accuracy increased with the distance between electrodes, while at higher current amplitudes, the accuracy was nearly 100% already for the shortest separation.

Significance

Optic nerve’s intraneural stimulation with the OpticSELINE induced discernible cortical activity patterns. These results represent a leap forward for intraneural optic nerve stimulation towards artificial vision.
The strange role of brain lesion size in cognitive neuropsychology
Authors: Sperber Christoph
Published: March 2021

The size of brain lesions is a variable that is frequently considered in cognitive neuropsychology. In particular, lesion-deficit inference studies often control for lesion size, and the association of lesion size with post-stroke cognitive deficits and its predictive value are studied. In the present article, the role of lesion size in cognitive deficits and its computational or design-wise consideration is discussed and questioned. First, I argue that the commonly discussed role or effect of lesion size in cognitive deficits eludes us. A generally valid understanding of the causal relation of lesion size, lesion location, and cognitive deficits is unachievable. Second, founded on the theory of covariate control, I argue that lesion size control is no valid covariate control. Instead, it is identified as a procedure with only situational benefits, which is supported by empirical data. This theoretical background is used to suggest possible research practices in lesion-deficit inference, post-stroke outcome prediction, and behavioural studies. Last, control for lesion size is put into a bigger methodological and also historical context – it is identified to relate to a long-known association problem in neuropsychology, which was previously discussed from the perspectives of a mislocalisation in lesion-deficit mapping and the symptom complex approach.

Highlights

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Lesion size is a factor that is often considered or controlled in neuropsychology

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No general causal relation between lesion size, lesion location and deficit exists

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Lesion size in brain mapping, outcome prediction and behavioural study is discussed

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Lesion size control is no valid covariate control

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Practical suggestions and guidelines how to consider lesion size are provided
Pathogenesis-related protein 1 (PR-1) genes in soybean: genome-wide identification, structural analysis and expression profiling under multiple biotic and abiotic stresses
Authors: Almeida-Silva Fabricio , Venancio Thiago M.
Published: March 2021

Plant pathogenesis-related (PR) proteins are a large group of proteins, classified in 17 families, that are induced by pathological conditions. Here, we characterized the soybean PR-1 (GmPR-1) gene repertoire at the sequence, structural and expression levels. We found 24 GmPR-1 genes, clustered in two phylogenetic groups. GmPR-1 genes are under strong purifying selection, particularly those that emerged by tandem duplications. GmPR-1 promoter regions are abundant in cis-regulatory elements associated with major stress-related transcription factor families, namely WRKY, ERF, HD-Zip, C2H2, NAC, and GATA. We observed that 23 GmPR-1 genes are induced by stress conditions or exclusively expressed upon stress. We explored 1972 transcriptome samples, including 26 stress conditions, revealing that most GmPR-1 genes are differentially expressed in a plethora of biotic and abiotic stresses. Our findings highlight stress-responsive GmPR-1 genes with potential biotechnological applications, such as the development of transgenic lines with increased resistance to biotic and abiotic stresses.
Quantitative detection of SARS-CoV-2 B.1.1.7 variant in wastewater by allele-specific RT-qPCR
Authors: Lee Wei Lin , McElroy Kyle A , Armas Federica , Imakaev Maxim , Gu Xiaoqiong , Duvallet Claire , Chandra Franciscus , Chen Hongjie , Leifels Mats , Mendola Samuel , Floyd-O’Sullivan Róisín , Powell Morgan M , Wilson Shane T , Wu Fuqing , Xiao Amy , Moniz Katya , Ghaeli Newsha , Matus Mariana , Thompson Janelle , Alm Eric J
Published: March 2021

Wastewater-based epidemiology (WBE) has emerged as a critical public health tool in tracking the SARS-CoV-2 epidemic. Monitoring SARS-CoV-2 variants of concern in wastewater has to-date relied on genomic sequencing, which lacks sensitivity necessary to detect low variant abundances in diluted and mixed wastewater samples. Here, we develop and present an open-source method based on allele specific RT-qPCR (AS RT-qPCR) that detects and quantifies the B.1.1.7 variant, targeting spike protein mutations at three independent genomic loci highly predictive of B.1.1.7 (HV69/70del, Y144del, and A570D). Our assays can reliably detect and quantify low levels of B.1.1.7 with low cross-reactivity, and at variant proportions between 0.1% and 1% in a background of mixed SARS-CoV-2. Applying our method to wastewater samples from the United States, we track B.1.1.7 occurrence over time in 19 communities. AS RT-qPCR results align with clinical trends, and summation of B.1.1.7 and wild-type sequences quantified by our assays strongly correlate with SARS-CoV-2 levels indicated by the US CDC N1/N2 assay. This work paves the path for rapid inexpensive surveillance of B.1.1.7 and other SARS-CoV-2 variants in wastewater.
Delayed dosing of minocycline plus N-acetylcysteine reduces neurodegeneration in distal brain regions and restores spatial memory after experimental traumatic brain injury
Authors: Whitney Kristen , Nikulina Elena , Rahman Syed N. , Alexis Alisia , Bergold Peter J.
Published: March 2021

Multiple drugs to treat traumatic brain injury (TBI) have failed clinical trials. Most drugs lose efficacy as the time interval increases between injury and treatment onset. Insufficient therapeutic time window is a major reason underlying failure in clinical trials. Few drugs have been developed with therapeutic time windows sufficiently long enough to treat TBI because little is known about which brain functions can be targeted if therapy is delayed hours to days after injury. We identified multiple injury parameters that are improved by first initiating treatment with the drug combination minocycline (MINO) plus N-acetylcysteine (NAC) at 72 hours after injury (MN72) in a mouse closed head injury (CHI) experimental TBI model. CHI produces spatial memory deficits resulting in impaired performance on Barnes maze, hippocampal neuronal loss, and bilateral damage to hippocampal neurons, dendrites, spines and synapses. MN72 treatment restores Barnes maze acquisition and retention, protects against hippocampal neuronal loss, limits damage to dendrites, spines and synapses, and accelerates recovery of microtubule associated protein 2 (MAP2) expression, a key protein in maintaining proper dendritic architecture and synapse density. These data show that in addition to the structural integrity of the dendritic arbor, spine and synapse density can be successfully targeted with drugs first dosed days after injury. Retention of substantial drug efficacy even when first dosed 72 hours after injury makes MINO plus NAC a promising candidate to treat clinical TBI.
Orthogonal neural codes for phonetic features in the infant brain
Authors: Gennari Giulia , Marti Sébastien , Palu Marie , Fló Ana , Dehaene-Lambertz Ghislaine
Published: March 2021

Creating invariant representations from an ever-changing speech signal is a major challenge for the human brain. Such an ability is particularly crucial for preverbal infants who must discover the phonological, lexical and syntactic regularities of an extremely inconsistent signal in order to acquire language. Within visual perception, an efficient neural solution to overcome signal variability consists in factorizing the input into orthogonal and relevant low-dimensional components. In this study we asked whether a similar neural strategy grounded on phonetic features is recruited in speech perception.

Using a 256-channel electroencephalographic system, we recorded the neural responses of 3-month-old infants to 120 natural consonant-vowel syllables with varying acoustic and phonetic profiles. To characterize the specificity and granularity of the elicited representations, we employed a hierarchical generalization approach based on multivariate pattern analyses. We identified two stages of processing. At first, the features of manner and place of articulation were decodable as stable and independent dimensions of neural responsivity. Subsequently, phonetic features were integrated into phoneme-identity (i.e. consonant) neural codes. The latter remained distinct from the representation of the vowel, accounting for the different weights attributed to consonants and vowels in lexical and syntactic computations.

This study reveals that, despite the paucity of articulatory motor plans and productive skills, the preverbal brain is already equipped with a structured phonetic space which provides a combinatorial code for speech analysis. The early availability of a stable and orthogonal neural code for phonetic features might account for the rapid pace of language acquisition during the first year.

SIGNIFICANCE STATEMENT

For adults to comprehend spoken language, and for infants to acquire their native tongue, it is fundamental to perceive speech as a sequence of stable and invariant segments despite its extreme acoustic variability. We show that the brain can achieve such a critical task thanks to a factorized representational system which breaks down the speech input into minimal and orthogonal components: the phonetic features. These elementary representations are robust to signal variability and are flexibly recombined into phoneme-identity percepts in a secondary processing phase. In contradiction with previous accounts questioning the availability of authentic phonetic representations in early infancy, we show that this neural strategy is implemented from the very first stages of language development.
Numerosity tuning in human association cortices and local image contrast representations in early visual cortex
Authors: Paul Jacob M. , van Ackooij Martijn , ten Cate Tuomas C. , Harvey Ben M.
Published: March 2021

Human early visual cortex response amplitudes monotonically increase with numerosity (object number), regardless of object size and spacing. However, numerosity is typically considered a high-level visual or cognitive feature, while early visual responses follow image contrast in the spatial frequency domain. We found that, at fixed contrast, aggregate Fourier power (at all orientations and spatial frequencies) followed numerosity closely but nonlinearly with little effect of object size, spacing or shape. This would allow straightforward numerosity estimation from spatial frequency domain image representations. Using 7T fMRI, we showed monotonic responses originate in primary visual cortex (V1) at the stimulus’s retinotopic location. Responses here and in neural network models followed aggregate Fourier power more closely than numerosity. Truly numerosity tuned responses emerged after lateral occipital cortex and were independent of retinotopic location. We propose numerosity’s straightforward perception and neural responses may have built on behaviorally beneficial spatial frequency analyses in simpler animals.
Stand-alone lipoylated H-protein of the glycine cleavage system enables glycine cleavage and the synthesis of glycine from one-carbon compounds in vitro
Authors: Xu Yingying , Li Yuchen , Zhang Han , Nie Jinglei , Ren Jie , Wang Wei , Zeng An-Ping
Published: March 2021

H-protein, one of the four component proteins (H, T, P and L) of glycine cleavage system (GCS), is generally considered a shuttle protein interacting with the other three GCS-proteins via a lipoyl swinging arm. We report that without P-, T- and L-proteins, lipoylated H-protein (Hlip) enables GCS reactions in both glycine cleavage and synthesis directions in vitro. This apparent catalytic activity is closely related to the cavity on the H-protein surface where the lipoyl arm is attached. Heating or mutation of selected residues in the cavity destroys or reduces the stand-alone activity of Hlip, which can be restored by adding the other three GCS-proteins. Systematic study of the Hlip-catalyzed overall GCS reactions and the individual reaction steps provides a first step towards understanding the stand-alone function of Hlip. The results in this work provide some inspiration for further understanding the mechanism of the GCS and give some interesting implications on the evolution of the GCS.

Significance statement

Glycine cleavage system (GCS) plays central roles in C1 and amino acids metabolisms and the biosynthesis of purines and nucleotides. Manipulations of GCS are desired to promote plant growth or to treat serious pathophysiological processes such as aging, obesity and cancers. Reversed GCS reactions form the core of the reductive glycine pathway (rGP), one of the most promising pathway for the assimilation of formate and CO2 in the emerging C1-synthetic biology. H-protein, one of the four GCS component proteins (H, T, P and L) is generally considered a shuttle protein interacting with the other three proteins via a lipoyl swinging arm. Here, we discovered that without P-, T- and L-proteins, H-protein alone can catalyze GCS reactions in both glycine cleavage and synthesis directions in vitro. The surprising catalytic activities are related to a structural region of H-protein which can be manipulated. The results have impacts on engineering GCS to treat related diseases, to improve photorespiration, and to efficiently use C1-carbon for biosynthesis.
Extended-Ensemble Docking to Probe Evolution of Ligand Binding Sites During Large-Scale Structural Changes of Proteins
Authors: Kapoor Karan , Thangapandian Sundar , Tajkhorshid Emad
Published: March 2021

Proteins can sample a broad landscape as they undergo conformational transition between different functional states. As key players in almost all cellular processes, proteins are important drug targets. Considering the different conformational states of a protein is therefore central for a successful drug-design strategy. Here we introduce a novel docking protocol, termed as extended-ensemble docking, pertaining to proteins that undergo large-scale (global) conformational changes during their function. In its application to multidrug ABC-transporter P-glycoprotein (Pgp), extensive non-equilibrium molecular dynamics simulations employing system-specific collective variables capturing the alternate access mechanism of Pgp, are first used to construct the transition cycle of the transporter. An extended set of conformational states representing the full transition between the inward- and the outward-facing states of Pgp, is then used to seed high-throughput docking calculations of a set of known substrates, non-substrates, and modulators of the transporter. Large differences are observed in the predicted binding affinities to the conformational ensemble, with compounds showing stronger binding affinities to intermediate conformations compared to the starting crystal structure. Hierarchical clustering of the individual binding modes of the different compounds shows all ligands preferably bind to the large central cavity of the protein, formed at the apex of the transmembrane domain (TMD), whereas only small binding populations are observed in the previously described R and H sites present within the individual TMD leaflets. Based on the results, the central cavity is further divided into two major subsites: first subsite preferably binds smaller substrates and high-affinity inhibitors, whereas the second one shows preference for larger substrates and low-affinity modulators. These central sites along with the low-affinity interaction sites present within the individual TMD leaflets may respectively correspond to the proposed high- and low-affinity binding sites in Pgp. We propose further optimization strategy for developing more potent inhibitor of Pgp, based on increasing its specificity to the extended ensemble of the protein instead of using a single protein structure, as well as its selectivity for the high-affinity binding site. In contrast to earlier in-silico studies using single static structures of Pgp, our results show better agreement with experimental studies, pointing to the importance of incorporating the global conformational flexibility of proteins in future drug-discovery endeavors.
Differential expression of single-cell RNA-seq data using Tweedie models
Authors: Mallick Himel , Chatterjee Suvo , Chowdhury Shrabanti , Chatterjee Saptarshi , Rahnavard Ali , Hicks Stephanie C.
Published: March 2021

Summary

The performance of computational methods and software to identify differentially expressed genes in single-cell RNA-sequencing (scRNA-seq) has been shown to be influenced by several factors, including the choice of the normalization method used and the choice of the experimental platform (or library preparation protocol) to profile gene expression in individual cells. Currently, it is up to the practitioner to choose the most appropriate differential expression (DE) method out of over 100 DE tools available to date, each relying on their own assumptions to model scRNA-seq data. Here, we propose to use generalized linear models with the Tweedie distribution that can flexibly capture a large dynamic range of observed scRNA-seq data across experimental platforms induced by heavy tails, sparsity, or different count distributions to model the technological variability in scRNA-seq expression profiles. We also propose a zero-inflated Tweedie model that allows zero probability mass to exceed a traditional Tweedie distribution to model zero-inflated scRNA-seq data with excessive zero counts. Using both synthetic and published plate- and droplet-based scRNA-seq datasets, we performed a systematic benchmark evaluation of more than 10 representative DE methods and demonstrate that our method (Tweedieverse) outperforms the state-of-the-art DE approaches across experimental platforms in terms of statistical power and false discovery rate control. Our open-source software (R package) is available athttps://github.com/himelmallick/Tweedieverse.
Imipramine and olanzapine block apoE4-catalyzed polymerization of Aβ and show evidence of improving Alzheimer’s disease cognition
Authors: Johnson Noah R. , Wang Athena C.-J. , Coughlan Christina , Sillau Stefan , Lucero Esteban , Viltz Lisa , Markham Neil , Allen Cody , Dhanasekaran A. Ranjitha , Chial Heidi J. , Potter Huntington
Published: March 2021

The apolipoprotein E (APOE) ε4 allele confers the strongest risk for late-onset Alzheimer’s disease (AD) besides age itself, but the mechanism(s) underlying this risk are debated. The critical test of any proposed AD mechanism is whether it leads to effective treatments. We developed a high-throughput assay to identify inhibitors of apoE4-catalyzed polymerization of the amyloid β (Aβ) peptide into neurotoxic fibrils. Screening a human drug library, we identified five non-toxic, blood-brain-barrier-permeable hit compounds that reduced apoE4-promoted Aβ and tau neuropathology in cultured neurons. Two hit compounds, imipramine and olanzapine, but not other (non-hit) antipsychotics or antidepressants, when prescribed to AD patients for their normal clinical indications, led to improvements in cognition and clinical diagnosis. Imipramine and olanzapine have no structural, functional, or clinical similarities other than their ability to inhibit apoE4-catalyzed Aβ polymerization, thus identifying this mechanism as an essential contribution of apoE4 to AD.

One Sentence Summary

High-throughput drug screens, studies in Alzheimer’s disease cell culture models, and analyses of human clinical data identified inhibitors of the apoE4-Aβ interaction as a novel class of Alzheimer’s disease therapeutics.
A Deep Reinforcement Learning based approach for movement training of neuro-musculoskeletal systems
Authors: Iyengar Raghu Sesha , Mallampalli Kapardi , Raghavan Mohan
Published: March 2021

Mechanisms behind neural control of movement have been an active area of research. Goal-directed movement is a common experimental paradigm used to understand these mechanisms and relevant neural pathways. In this paper, we attempt to build an anatomically and physiologically realistic model of spinal cord along with the relevant circuitry and interface it with a musculoskeletal model of an upper limb, using the NEUROiD platform. The neuronal model (simulated on NEURON) and the musculoskeletal model (simulated on OpenSim) are cosimulated on NEUROiD. We then use Deep Reinforcement Learning to obtain a functionally equivalent model of the supraspinal components and the descending cortical activations feeding into the last-order interneurons and motoneurons. Uniplanar goal directed movement of the elbow joint was used as the goal for the learning algorithm. Key aspects of our work are: (1) Our solution converges naturally to the triphasic response observed in goal directed tasks (2) Gradually increasing the complexity of task helped in faster learning (3) In response to corticospinal inputs, our model could produce movements on which it was not explicitly trained, but were close to the trained movements. Being able to generate movements on which the model was not explicitly trained, implies that the movement repertoire that a biomimetic model needs to learn, could be much smaller than the complete set of movements it can execute. We hope that this will lead to building larger and complex biomimetic systems, one block at a time.
Maxent modeling for predicting the potential distribution of global talaromycosis
Authors: Wei Wudi , He Jinhao , Ning Chuanyi , Xu Bo , Wang Gang , Lai Jingzhen , Jiang Junjun , Ye Li , Liang Hao
Published: March 2021

Talaromycosis, an invasive mycosis caused by Talaromyces marneffei (Tm), has rapidly increased in recent years, becoming an emerging pathogenic fungal disease. However, The driving factors and potential distribution of global talaromycosis is still unclear. Here, we developed maxent ecology model using environmental variables, Rhizomys distribution and HIV/AIDS epidemic to forecast ecological niche of talaromycosis worldwhile, as well as Identify the drivering factors. The constructed model had excellent performance with the area under the curve (AUC) of the receiver operating curve (ROC) of 0.997 in training data and 0.991 in testing data. Our model revealed that Rhizomys distribution, mean temperature of warmest quarter, precipitation of wettest month, HIV/AIDS epidemic and mean temperature of driest quarter were the top 5 important variables affecting talaromycosis distribution. In addition to traditional talaromycosis epidemic areas (South of the Yangtze River in China, Southeast Asian and North and Northeast India), our model also identified other potential epidemic regions, inculding parts of the North of the Yangtze River, Central America, West Coast of Africa, East Coast of South America, the Korean Peninsula and Japan. Our findings has redefined global talaromycosis, discovered hidden high-risk areas and prorvided insights about driving factors of talaromycosis distribution, which will help inform surveillance strategies and improve the effectiveness of public health interventions against Tm infections.

Author Summary

Our study aims to explore the spatial ecology of talaromycosis worldwhile. The diseases burden of Talaromycosis, a neglected zoonotic disease, is continuously rising in recent years because of the sheer size of susceptible population in the setting of increased globalization, rising HIV prevalence, and emerging iatrogenic immunodeficiency conditions. Here, we used historic reported talaromycosis cases from 1964 to 2017, combined with environmental factors, Rhizomys distribution and HIV/AIDS epidemic to build an maxent ecology model to define the ecological niche of talaromycosis, then predicting the potential distribution of the disease. The ecological niche of talaromycosis is characterized by a concentrated distribution, which can be cognitively divided into two regions: traditional talaromycosis epidemic areas (South of the Yangtze River in China, Southeast Asian and North and Northeast India), while other potential epidemic regions were predicted in parts of the North of the Yangtze River, Central America, West Coast of Africa, East Coast of South America, the Korean Peninsula and Japan. Our model also identified 5 driving factors affecting talaromycosis distribution. These findings will help demonstrate the global distribution of talaromycosis, discover hidden high-risk areas, and improve the effectiveness of public health interventions against Tm infections.
Human α-Synuclein Inhibits Platelets Aggregationin vitroby Interfering with the α-Thrombin/Protease-Activated Receptor 1 Functional Axis
Authors: Pontarollo Giulia , Acquasaliente Laura , Radu Claudia Maria , Peterle Daniele , Artusi Ilaria , Pagotto Anna , Uliana Federico , Simioni Paolo , Negro Alessandro , De Filippis Vincenzo
Published: March 2021

α-Synuclein (αSyn) is a small (140 amino acids) disordered, acidic (pI: 4.7) protein, highly conserved in vertebrates and implicated in the pathogenesis of Parkinson’s disease (PD), a neurodegenerative disease characterized by the deposition of αSyn amyloid fibrils in dopaminergic neurons. Beyond the central nervous system, significant expression of αSyn has also been measured in the blood (~1 μM), where platelets are the main cellular hosts of αSyn. Although the pathological implication of αSyn in PD is widely accepted, the physiological role of blood αSyn is still elusive. Starting from the notion that platelets are either the major cellular reservoir of αSyn in the blood and, concomitantly, act as key players in hemostasis, being activated also by α-thrombin (αT)viacleavage of protease-activated receptors (PARs), we decided to investigate the possibility that αSyn could modulate platelet activation by interfering with the αT-PAR functional axis. Using multiple electrode aggregometry, i.e. a fast and specific platelet-function-testing method, as well as steady-state fluorescence spectroscopy, surface plasmon resonance, and fluorescence microscopy, we show here that monomeric αSyn functions as a negative regulator of αT-mediated platelets activation. αSyn acts either directly,viacompetitive inhibition of PAR1 activation by αT and TRAP6 agonist, and indirectly, by scavenging αT on the platelet plasma membrane. A simple electrostatic model of αSyn platelet antiaggregating effect is proposed and the possible role of the protein at the interplay of amyloidosis and thrombosis is discussed.
Sulfate adenylyl transferase kinetics and mechanisms of metabolic inhibitors of microbial sulfate respiration
Authors: Carlson Hans K. , Youngblut Matthew D. , Redford Steven A. , Williamson Adam J. , Coates John D.
Published: March 2021

Sulfate analog oxyanions that function as selective metabolic inhibitors of dissimilatory sulfate reducing microorganisms (SRM) are widely used in ecological studies and industrial applications. As such, it is important to understand the mode of action and mechanisms of tolerance or adaptation to these compounds. Different oxyanions vary widely in their inhibitory potency and mechanism of inhibition, but current evidence suggests that the sulfate adenylyl transferase/ATP sulfurylase (Sat) enzyme is an important target. We heterologously expressed and purified the Sat from the model SRM,Desulfovibrio alaskensisG20. With this enzyme we determined the turnover kinetics (kcat, KM) for alternative substrates (molybdate, selenate, arsenate, monofluorophosphate, and chromate) and inhibition constants (KI) for competitive inhibitors (perchlorate, chlorate, and nitrate). These measurements enable the first quantitative comparisons of these compounds as substrates or inhibitors of a purified Sat from a respiratory sulfate reducer. We compare predicted half-maximal inhibitory concentrations (IC50) based on Sat kinetics with measured IC50values againstD. alaskensisG20 growth and discuss our results in light of known mechanisms of sensitivity or resistance to oxyanions. This analysis helps with the interpretation of recent adaptive laboratory evolution studies and illustrates the value of interpreting gene-microbe-environment interactions through the lens of enzyme kinetics.
A novel domain within the CIL regulates egress of IFITM3 from the Golgi and prevents its deleterious accumulation in this apparatus
Authors: Zhong Li , Uzbekov Rustem , Journo Chloé , Roingeard Philippe , Cimarelli Andrea
Published: March 2021

The InterFeron-Induced TransMembrane proteins (IFITMs) are broad viral inhibitors that protect cells by preventing viral-to-cellular membrane fusion and they belong to the dispanin/CD225 family that includes vesicle trafficking regulators and proteins of unknown functions into four subfamilies (A-D). In this study, we uncover a novel domain that regulates the egress of IFITM3 from the Golgi and that is required to prevent IFITM3-driven v- to t-SNAREs membrane fusion inhibition and Golgi dysfunctions.

The S-x-K-x-R-D domain is conserved among vertebrate members of the dispanin/CD225 A subfamily that regroups all IFITMs and through the study of mutations identified in patients affected by paroxysmal kinesigenic dyskinesia (PKD), we determine that it is functionally conserved also in PRRT2, member of the B subfamily.

Overall, our study defines a novel domain that regulates the egress of dispanin/CD225 members from the Golgi and stresses the importance that regulation of this process bears to preserve the functions of this apparatus.
A disease-linked lncRNA mutation in RNase MRP inhibits ribosome synthesis
Authors: Robertson Nic , Shchepachev Vadim , Wright David , Turowski Tomasz W. , Spanos Christos , Helwak Aleksandra , Zamoyska Rose , Tollervey David
Published: March 2021

RMRPencodes a non-coding RNA forming the core of the RNase MRP ribonucleoprotein complex. Mutations cause Cartilage Hair Hypoplasia (CHH), characterized by skeletal abnormalities and impaired T cell activation. Yeast RNase MRP cleaves a specific site in the pre-ribosomal RNA (pre-rRNA) during ribosome synthesis. CRISPR-mediated disruption ofRMRPin human cells lines caused growth arrest, with pre-rRNA accumulation. Here, we analyzed disease-relevant primary cells, showing that mutations inRMRPimpair mouse T cell activation and delay pre-rRNA processing. Patient-derived human fibroblasts with CHH-linked mutations showed similar pre-rRNA processing delay. Human cells engineered with the most common CHH mutation (70AGinRMRP) show specifically impaired pre-rRNA processing, resulting in reduced mature rRNA and a reduced ratio of cytosolic to mitochondrial ribosomes. Moreover, the 70AGmutation caused a reduction in intact RNase MRP complexes. Together, these results indicate that CHH is a ribosomopathy, and the first processing-specific human disorder to be described.

Highlights

Mutations inRMRPlncRNA impair pre-rRNA processing and T cell activation

Patient derived fibroblasts show impaired pre-rRNA processing

Cells with the most common disease-linked mutation have specific processing defects

Cytoplasmic ribosomes and intact RNase MRP complexes are also reduced in these cells
The institutional logic of the sustainable organisation: the case of a chocolate supply network
Authors: McLoughlin Kate , Meehan Joanne
Published: March 2021

Purpose

The purpose of this paper is to examine how, and by whom, institutional logics are determined in the action of sustainable organisation. The authors analyse a supply chain network structure to understand how multiple stakeholders' perceptions of sustainability emerge into a dominant logic and diffuse across an organisational field.

Design/methodology/approach

Stakeholder network theory provides novel insights into emerging logics within a chocolate supply chain network. Semi-structured interviews with 35 decision-makers were analysed alongside 269 company documents to capture variations in emergent logics. The network was mapped to include 63 nodes and 366 edges to analyse power structure and mechanisms.

Findings

The socio-economic organising principles of sustainable organisation, their sources of power and their logics are identified. Economic and social logics are revealed, yet the dominance of economic logics creates risks to their coexistence. Logics are largely shaped in pre-competitive activities, and resource fitness to collaborative clusters limits access for non-commercial actors.

Research limitations/implications

Powerful firms use network structures and collaborative and concurrent inter-organisational relationships to define and diffuse their conceptualisation of sustainability and restrict competing logics.

Originality/value

This novel study contributes to sustainable supply chain management (SSCM) through presenting the socio-economic logic as a new conceptual framework to understand the action of sustainable organisation. The identification of sophisticated mechanisms of power and hegemonic control in the network opens new research agendas.
Recent trends and role of large area flexible electronics in shape sensing application – a review
Authors: Shaik Riyaz Ali , Rufus Elizabeth
Published: March 2021

Purpose

This paper aims to review the shape sensing techniques using large area flexible electronics (LAFE). Shape perception of humanoid robots using tactile data is mainly focused.

Design/methodology/approach

Research papers on different shape sensing methodologies of objects with large area, published in the past 15 years, are reviewed with emphasis on contact-based shape sensors. Fiber optics based shape sensing methodology is discussed for comparison purpose.

Findings

LAFE-based shape sensors of humanoid robots incorporating advanced computational data handling techniques such as neural networks and machine learning (ML) algorithms are observed to give results with best resolution in 3D shape reconstruction.

Research limitations/implications

The literature review is limited to shape sensing application either two- or three-dimensional (3D) LAFE. Optical shape sensing is briefly discussed which is widely used for small area. Optical scanners provide the best 3D shape reconstruction in the noncontact-based shape sensing; here this paper focuses only on contact-based shape sensing.

Practical implications

Contact-based shape sensing using polymer nanocomposites is a very economical solution as compared to optical 3D scanners. Although optical 3D scanners can provide a high resolution and fast scan of the 3D shape of the object, they require line of sight and complex image reconstruction algorithms. Using LAFE larger objects can be scanned with ML and basic electronic circuitory, which reduces the price hugely.

Social implications

LAFE can be used as a wearable sensor to monitor critical biological parameters. They can be used to detect shape of large body parts and aid in designing prosthetic devices. Tactile sensing in humanoid robots is accomplished by electronic skin of the robot which is a prime example of human–machine interface at workplace.

Originality/value

This paper reviews a unique feature of LAFE in shape sensing of large area objects. It provides insights from mechanical, electrical, hardware and software perspective in the sensor design. The most suitable approach for large object shape sensing using LAFE is also suggested.
Natural resource governance, accountability and legitimising propensity: insights from Ghana's oil and gas sector
Authors: Asare Emmanuel , Burton Bruce , Dunne Theresa
Published: March 2021

Purpose

This study explores Ghanaian views about accountability discharge by firms and government in the context of the nation's newly discovered oil and gas resources. The research focusses on a range of issues relating to stakeholder interaction, communication flows and the impact of decision-making on Ghanaian lives, as perceived by individuals on the ground.

Design/methodology/approach

The paper adapts elements of legitimacy theory to interpret the outcome of a series of semi-structured interviews with members of key accountee and accountor groups including citizens and representatives of the state and private firms in the oil and gas industry in Ghana.

Findings

The results indicate that rather than attempting to effect substantive accountability discharge, Ghana's government and oil and gas firms employ a wide range of legitimation strategies despite the apparently complete absence of the accountee power normally seen as driving the need for social contract repair.

Research limitations/implications

The findings suggest that accountability discharge in Ghana is cursory at best, with several legitimising strategies in evidence. The representatives from state institutions appear to share some of the concerns, suggesting that the problems are entrenched and will require robust enforcement of a strengthened regulatory approach to effect meaningful change.

Originality/value

This paper contributes to the literature on the discharge of institutional accountability by building on earlier conceptualisations of legitimacy theory to explore perceptions around a recent natural resource discovery. The analysis highlights grave concerns regarding the behaviour of state and corporate actors, one that runs counter to sub-Saharan African tradition.
Mergers may enhance the legitimacy of community health organisations in neoliberal environments
Authors: Roussy Veronique , Russell Grant , Livingstone Charles , Riley Therese
Published: March 2021

Purpose

Comprehensive primary health care (PHC) models are seldom implemented in high income countries, in part due to their contested legitimacy in neoliberal policy environments. This article explores how merging affected the perceived legitimacy of independent community health organisations in Victoria, Australia, in providing comprehensive PHC services.

Design/methodology/approach

A longitudinal follow-up study (2–3 years post-merger) of two amalgamations among independent community health organisations from the state of Victoria, Australia, was conducted. This article explores the perceived effects of merging on (1) the pragmatic, normative and cognitive legitimacy of studied organisations and (2) the collective legitimacy of these organisations in Victoria's health care system. Data were collected through 19 semi-structured interviews with key informants and subjected to template and thematic analyses.

Findings

Merging enabled individual organisations to gain greater overall legitimacy as regional providers of comprehensive PHC services and thus retain some capacity to operationalise a social model of health. Normative legitimacy was most enhanced by merging, through acquisition of a large organisational size and adoption of business practices favoured by neoliberal norms. However, mergers may have destabilised the already contested cognitive legitimacy of community health services as a group of organisations and as a comprehensible state-wide platform of service delivery.

Practical implications

Over-reliance on individual organisational behaviour to maintain the legitimacy of comprehensive PHC as a model of organising health and social care could lead to inequities in access to such models across communities.

Originality/value

This study shows that organisations can manage their perceived legitimacy in order to ensure the survival of their preferred model of service delivery.
Realities of illusion: tracing an anthropology of the unreal from Torres Strait to virtual reality
Authors: Messeri Lisa
Published: March 2021

This article examines how perceptual illusions become reliable markers of truth in the context of experimental psychology. As laboratory tools, illusions travel across time, place, and media: from the Torres Strait expedition at the close of the nineteenth century to a contemporary psychology lab that utilizes virtual reality. In this historical and ethnographic study, something that might otherwise be considered misleading (illusion) becomes an epistemological guide. Illusion takes on a reality and in so doing raises questions about what ought and ought not to be considered real. This research thus joins other anthropologies that expand what counts as ‘the real’. These anthropologies of the unreal are proliferating of late and breathe hope back into human and nonhuman futures by reconsidering what constitutes being in the world. The reality of illusion highlights a phenomenological position in which reality is the world as perceptually experienced. Further, as this investigation unfolds in the laboratory, it becomes clear that the unreal is not set apart from but incorporated into knowledge systems.
Editorial
Authors: Tarran Brian
Published: March 2021

Lessons from disruption.
Towards understanding bold behaviour of large carnivores: the case of brown bears in human‐modified landscapes
Authors: Bombieri G. , Penteriani V , Delgado M. del Mar , Groff C. , Pedrotti L. , Jerina K.
Published: March 2021

Human–wildlife conflicts sometimes involve bold animals that do not fear humans and their activities. Such behaviour is detrimental to both wildlife and people and may lead to conflicts, which can be especially serious for large carnivores. Like most wildlife, these species have adapted to live in highly humanized landscapes by adopting human avoidance behaviours. However, bold individuals exist, which represent a main cause of conflicts, public fear and negative attitudes, that greatly influence management and conservation actions. Although costly decisions are constantly made to deal with such individuals, evidence‐based knowledge of their behaviour, that is how and when they move, especially in relation to human activities, is lacking. We analysed telemetry data of brown bears (Ursus arctos) that were GPS‐collared across Slovenia and Trentino (Italy) to explore spatial behaviour and rhythms of activity of bears that were identified as bold by managers and to assess if and how their behaviour differs from that of their ‘non‐bold’ conspecifics (hereafter, control individuals). Because other factors such as sex and age of the bear, season, daytime and region may affect behaviour, we also included these variables in our analyses. On one hand, bold bears were more active at the daytime and used open areas considerably more often than control bears. On the other hand, although differences in distance to settlements and roads, movement rates and daily home ranges were also found, they were not as pronounced as expected. Instead, other factors were found to affect bear behaviour and, most importantly, we found strong inter‐individual differences in all behaviours. Such results suggest that, although bold bears have some behavioural attributes in common that distinguish them from control bears, each individual differs from one another. Our study represents a first step towards understanding bold bears’ behaviour and provide novel evidence‐based knowledge that can help to better know and manage these individuals.
Origin and distribution of facial nerve anatomy in van cats
Authors: Nur İsmail Hakkı , Pérez William , König Horst Erich
Published: March 2021

This study aims to reveal the morphological properties of facial nerve and the middle ear in Van cats. Study material was composed of 6 female Van cats. Dissections were performed under a Zoom Stereo Microscope. There was no plexus buccalis in Van cats. The chorda tympani was observed to pass through an opening in the tympanic cavity, emerge through a small opening just behind the retroarticular process, and join the lingual nerve. A rounded anatomical formation with a size of 2.75 ± 0.3 mm was found to be located within the mastoid process of the temporal bone between the facial nerve and the auricular branch of the vagus nerve. The stapes nerve was not present. The geniculate ganglion was very prominent and about 1.00 mm high. The deep petrosal nerve was observed to emerge from the plexus tympanicus. The bulla tympanica was 18.96 ± 0.10 mm long, 13.03 ± 0.20 mm wide and 13.16 ± 0.20 mm high. After leaving the mandibular nerve, the n.tensoris tympani coursed caudally around the a.maxillaris, formed an ansa, entered the tympanic cavity through the canalis musculotubarius and reached an end in the m. tensor tympani. Due to the scarcity of studies on the middle ears of Van cats, it is thought that this study will fill a gap in the field of veterinary anatomy.