bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Th1 bias in memory T cells corresponds with protection from reinfection inPlasmodiuminfection, and is regulated by T cell-intrinsic STAT3
Authors: Carpio Victor H. , Aussenac Florentin , Wilson Kyle D. , Villarino Alejandro V. , Dent Alexander L. , Stephens Robin
Published: August 2019

Hybrid Th1/Tfh cells (IFN-γ+IL-21+CXCR5+) predominate in response to persistent infections; however, molecular regulation of their function is poorly defined. In infection withPlasmodium spp, an IFN-γ+T helper-1 (Th1) response controls initial parasitemia, while antibody and IL-21+CXCR5+T follicular helper (Tfh) function effect final clearance. Here, we found that CD4-intrinsic Bcl6, Blimp-1 and STAT3 all regulate T-bet expression, which controls IFN-γ expression. While Bcl6 and Blimp-1 regulate the level of CXCR5, only T-bet and STAT3 affected the functional bias of the Th1/Tfh phenotype. Infected mice with STAT3-deficient T cells produced less antibody, and more IFN-γ+IL-21−CXCR5loT cells, significantly increasing protection from re-infection. Conversely, reduced Th1 bias in re-infected T-bet KO was reflected in prolonged secondary parasitemia. In summary, each feature of hybrid Th1/Tfh population inPlasmodiuminfection is uniquely regulated and the cytokine bias of memory T cells can be modified to enhance the effectiveness of the response.
Isolation of an antimicrobial resistant, biofilm forming,Klebsiella grimontiiisolate from a re-usable water bottle
Authors: Hubbard Alasdair TM , Reiné Jesús , Newire Enas , Wright Elli , Murphy Emma A , Hutton William , Roberts Adam P
Published: August 2019

A re-usable water bottle was swabbed as part of the citizen science project Swab and Send and aKlebsiella grimontiiisolate was recovered on chromogenic agar and designated SS141. Whole genome sequencing of SS141 showed it has the potential to be a human pathogen as it contains the biosynthetic gene cluster for the potent cytotoxin, kleboxymycin, and genes for other virulence factors. The genome also containsblaOXY-6-4 andfosAwhich is likely to explain the observed resistance to ampicillin, amoxicillin and fosfomycin. We have also shown that SS141 is a potent biofilm former, providing a reasonable explanation for its ability to colonise a re-usable water bottle. With the increasing use of re-usable water bottles as an alternative to disposables, and a strong forecast for growth in this industry over the next decade, this study highlights the need for cleanliness comparable to other re-usable culinary items.
Quantitative Cytogenetics Reveals Molecular Stoichiometry and Longitudinal Organization of Meiotic Chromosome Axes and Loops
Authors: Woglar Alexander , Yamaya Kei , Roelens Baptiste , Boettiger Alistair , Köhler Simone , Villeneuve Anne M
Published: August 2019

During meiosis, chromosomes adopt a specialized organization involving assembly of a cohesin-based axis along their lengths, with DNA loops emanating from this axis. We applied novel, quantitative and widely applicable cytogenetic strategies to elucidate the molecular bases of this organization usingC. elegans. Analyses of WT chromosomes andde novocircular mini-chromosomes revealed that meiosis-specific HORMA-domain proteins assemble into cohorts in defined numbers and co-organize the axis together with two functionally-distinct cohesin complexes (REC-8 and COH-3/4) in defined stoichiometry. We further found that REC-8 cohesins, which load during S phase and mediate sister chromatid cohesion, usually occur as individual complexes, supporting a model wherein sister cohesion is mediated locally by a single cohesin ring. REC-8 complexes are interspersed in an alternating pattern with cohorts of axis-organizing COH-3/4 complexes (averaging three per cohort), which are insufficient to confer cohesion but can bind to individual chromatids, suggesting a mechanism to enable formation of asymmetric sister chromatid loops. Indeed, immuno-FISH assays demonstrate frequent asymmetry in genomic content between the loops formed on sister chromatids. We discuss how features of chromosome axis/loop architecture inferred from our data can help to explain enigmatic, yet essential, aspects of the meiotic program.
In vitro and in silico modeling of cellular and matrix-related changes during the early phase of osteoarthritis
Authors: Weber Marie-Christin , Fischer Lisa , Damerau Alexandra , Ponomarev Igor , Pfeiffenberger Moritz , Gaber Timo , Götschel Sebastian , Lang Jens , Röblitz Susanna , Buttgereit Frank , Ehrig Rainald , Lang Annemarie
Published: August 2019

Objective

Understanding the pathophysiological processes of osteoarthritis (OA) require adequate model systems. Although different in vitro or in vivo models have been described, further comprehensive approaches are needed to study specific parts of the disease. This study aimed to combine in vitro and in silico modeling to describe cellular and matrix-related changes during the early phase of OA. We developed an in vitro OA model based on scaffold-free cartilage-like constructs (SFCCs), which was mathematically modeled using a partial differential equation (PDE) system to resemble the processes during the onset of OA.

Design

SFCCs were produced from mesenchymal stromal cells and analyzed weekly by histology and qPCR to characterize the cellular and matrix-related composition. To simulate the early phase of OA, SFCCs were treated with interleukin-1β (IL-1β), tumor necrosis factor α (TNFα) and examined after 3 weeks or cultivated another 3 weeks without inflammatory cytokines to validate the regeneration potential. Mathematical modeling was performed in parallel to the in vitro experiments.

Results

SFCCs expressed cartilage-specific markers, and after stimulation an increased expression of inflammatory markers, matrix degrading enzymes, a loss of collagen II (Col-2) and a reduced cell density was observed which could be partially reversed by retraction of stimulation. Based on the PDEs, the distribution processes within the SFCCs, including those of IL-1β, Col-2 degradation and cell number reduction was simulated.

Conclusions

By combining in vitro and in silico methods, we aimed to develop a valid, efficient alternative approach to examine and predict disease progression and new therapeutic strategies.
Stochasticity-induced stabilization in ecology and evolution
Authors: Dean Antony , Shnerb Nadav M.
Published: August 2019

The ability of random environmental variation to stabilize competitor coexistence was pointed out long ago and, in recent years, has received considerable attention. Here we suggest a novel and generic synthesis of stochasticity-induced stabilization (SIS) phenomena. The storage effect in the lottery model, together with other well-known examples drawn from population genetics, microbiology and ecology, are placed together, reviewed, and explained within a clear, coherent and transparent theoretical framework. Implementing the diffusion approximation we show that in all these systems (including discrete and continuous dynamics, with overlapping and non-overlapping generations) the ratio between the expected growth and its variance governs both qualitative and quantitative features of persistence and invasibility. We further clarify the relationships between bet-hedging strategies, generation time and SIS, study the dynamics of extinction when SIS fails and the explain effects of species richness and asymmetric competition on the stabilizing mechanism.
A biophysical model of striatal microcircuits suggests delta/theta-rhythmically interleaved gamma and beta oscillations mediate periodicity in motor control
Authors: Chartove Julia A. K. , McCarthy Michelle M. , Pittman-Polletta Benjamin R. , Kopell Nancy J.
Published: August 2019

Striatal oscillatory activity is associated with movement, reward, and decision-making, and observed in several interacting frequency bands. Local field potential recordings in rodent striatum show dopamine- and reward-dependent transitions between two states: a “spontaneous” state involving β (~15-30 Hz) and low γ (~40-60 Hz), and a state involving θ (~4-8 Hz) and high γ (~60-100 Hz) in response to dopaminergic agonism and reward. The mechanisms underlying these rhythmic dynamics, their interactions, and their functional consequences are not well understood. In this paper, we propose a biophysical model of striatal microcircuits that comprehensively describes the generation and interaction of these rhythms, as well as their modulation by dopamine. Building on previous modeling and experimental work suggesting that striatal projection neurons (SPNs) are capable of generating β oscillations, we show that networks of striatal fast-spiking interneurons (FSIs) are capable of generating δ/θ (ie, 2 to 6 Hz) and γ rhythms. Under simulated low dopaminergic tone our model FSI network produces low γ band oscillations, while under high dopaminergic tone the FSI network produces high γ band activity nested within a δ/θ oscillation. SPN networks produce β rhythms in both conditions, but under high dopaminergic tone, this β oscillation is interrupted by δ/θ-periodic bursts of γ-frequency FSI inhibition. Thus, in the high dopamine state, packets of FSI γ and SPN β alternate at a δ/θ timescale. In addition to a mechanistic explanation for previously observed rhythmic interactions and transitions, our model suggests a hypothesis as to how the relationship between dopamine and rhythmicity impacts motor function. We hypothesize that high dopamine-induced periodic FSI γ-rhythmic inhibition enables switching between β-rhythmic SPN cell assemblies representing the currently active motor program, and thus that dopamine facilitates movement in part by allowing for rapid, periodic shifts in motor program execution.

Author summary

Striatal oscillatory activity is associated with movement, reward, and decision-making, and observed in several interacting frequency bands. The mechanisms underlying these rhythmic dynamics, their interactions, and their functional consequences are not well understood. In this paper, we propose a biophysical model of striatal microcircuits that comprehensively describes the generation and interaction of striatal rhythms, as well as their modulation by dopamine. Our model suggests a hypothesis as to how the relationship between dopamine and rhythmicity impacts the function of the motor system, enabling rapid, periodic shifts in motor program execution.
A biomimetic electrical stimulation strategy to induce asynchronous stochastic neural activity
Authors: Formento Emanuele , D’Anna Edoardo , Gribi Sandra , Lacour Stéphanie P. , Micera Silvestro
Published: August 2019

Electrical stimulation is an effective method to communicate with the nervous system. Here, we demonstrate that current stimulation paradigms fail to reproduce the stochastic and asynchronous properties of natural patterns of neural activity, and introduce a novel biomimetic stimulation (BioS) strategy that overcomes these limitations. We hypothesized that high-frequency amplitude-modulated bursts of stimulation could induce asynchronous neural firings by distributing recruitment over the duration of a burst, without sacrificing the ability to precisely control neural activity. We tested this hypothesis using computer simulations and ex vivo experiments. We found that BioS bursts induce asynchronous, stochastic, yet controllable, neural activity. We established that varying the amplitude, duration, and repetition frequency of a BioS burst enables graded modulation of the number of recruited fibers, their firing rate, and the synchronicity of the responses. These results demonstrate an unprecedented level of control over artificially induced neural activity, enabling the design of next-generation biomimetic stimulation paradigms with potentially profound consequences for the field of neurostimulation.
A unified neurocognitive model of the anterior temporal lobe contributions to semantics, language, social behaviour & face recognition
Authors: Ding Junhua , Chen Keliang , Liu Haoming , Huang Lin , Chen Yan , Lv Yingru , Yang Qing , Guo Qihao , Han Zaizhu , Lambon Ralph Matthew. A.
Published: August 2019

Abstract

The anterior temporal lobes (ATL) have become a key brain region of interest in cognitive and clinical neuroscience. Contemporary explorations are founded upon neuropsychological investigations of semantic dementia (SD) that describe the patients’ selective semantic impairment and the variations in their language, behavioural and face recognition abilities. The purpose of this investigation was to generate a single unified model which captures the known cognitive-behavioural variations in SD, and integrates with the considerable database on healthy semantic function and other patient groups. A new analytical approach was able to capture the graded neuropsychological differences and map these to the patients’ distribution of frontotemporal atrophy. Multiple regression and principal component analyses confirmed that the degree of generalised semantic impairment was related to the patients’ total, bilateral ATL atrophy. Verbal production and word-finding abilities were related to total ATL atrophy as well as to the balance of left>right ATL atrophy. Behavioural apathy was found to relate positively to the degree of orbitofrontal atrophy and negatively to total temporal volumes. Disinhibited behaviour was related to right ATL and orbitofrontal atrophy and face recognition to right ATL volumes. Rather than positing mutually-exclusive sub-categories, the data-driven model repositions semantics, language, social behaviour and face recognition into a continuous frontotemporal neurocognitive space.
Evolutionary dynamics of microbial communities in bioelectrochemical systems
Authors: Szydlowski Lukasz , Sorokin Anatoly , Vasieva Olga , Boerner Susan , Fedorovich Veyacheslav , Goryanin Igor
Published: August 2019

Bio-electrochemical systems can generate electricity by virtue of mature microbial consortia that gradually and spontaneously optimize performance. To evaluate selective enrichment of these electrogenic microbial communities, five, 3-electrode reactors were inoculated with microbes derived from rice wash wastewater and incubated under a range of applied potentials. Reactors were sampled over a 12-week period and DNA extracted from anodal, cathodal, and planktonic bacterial communities was interrogated using a custom-made bioinformatics pipeline that combined 16S and metagenomic samples to monitor temporal changes in community composition. Some genera that constituted a minor proportion of the initial inoculum dominated within weeks following inoculation and correlated with applied potential. For instance, the abundance ofGeobacterincreased from 423-fold to 766-fold between −350 mV and −50 mV, respectively. Full metagenomic profiles of bacterial communities were obtained from reactors operating for 12 weeks. Functional analyses of metagenomes revealed metabolic changes between different species of the dominant genus,Geobacter, suggesting that optimal nutrient utilization at the lowest electrode potential is achieved via genome rearrangements and a strong inter-strain selection, as well as adjustment of the characteristic syntrophic relationships. These results reveal a certain degree of metabolic plasticity of electrochemically active bacteria and their communities in adaptation to adverse anodic and cathodic environments.
Engineering the smallest transcription factor: accelerated evolution of a 63-amino acid peptide dual activator-repressor
Authors: Brödel Andreas K. , Rodrigues Rui , Jaramillo Alfonso , Isalan Mark
Published: August 2019

Transcription factors control gene expression in all life. This raises the question of what is the smallest protein that can support such activity. In nature, Cro from bacteriophage λ is the smallest known repressor (66 amino acids; a.a.) but activators are typically much larger (e.g. λ cI, 237 a.a.). Indeed, previous efforts to engineer a minimal activator from Cro resulted in no activityin vivo. In this study, we show that directed evolution results in a new Cro activator-repressor that functions as efficiently as λ cI,in vivo. To achieve this, we develop Phagemid-Assisted Continuous Evolution: PACEmid. We find that a peptide as small as 63-a.a. functions efficiently as an activator and/or repressor. To our knowledge, this is the smallest protein gene regulator reported to date, highlighting the capacity of transcription factors to evolve from very short peptide sequences.
Astrocytes modulate baroreceptor reflex sensitivity at the level of the nucleus of the solitary tract
Authors: Mastitskaya Svetlana , Turovsky Egor , Marina Nephtali , Theparambil Shefeeq M. , Hadjihambi Anna , Ramage Andrew G. , Gourine Alexander V. , Hosford Patrick S.
Published: August 2019

Astrocytes play an important role in cardiovascular reflex integration at the level of the nucleus tractus solitarii (NTS). Existing reports from brainstem slice preparations suggest that astrocytes here respond to input from the solitary tract by increasing intracellular calcium. However, the physiological significance of this neuron-astrocyte signaling in vivo remains unknown. Here, we report that stimulation of the vagus nerve in an anesthetized rat induced rapid [Ca2+]i increases in astrocytes transduced to express calcium sensor GCaMP6. The receptors involved were determined using brainstem-derived astroglial cell cultures were loaded with [Ca2+] indicator Fura-2. 5-HT (10 µM) caused robust increases in [Ca2+]i, and pharmacological interrogation revealed the expression of functional 5-HT2A receptors. This observation was confirmed in vivo: intravenous administration of ketanserin decreased the magnitude of [Ca2+]i responses, induced by vagal afferent simulation, by ∼50%. However, the response was completely blocked by topical application of the AMPA receptor antagonist CNQX alone. To investigate the role of astrocyte-neuron communication, the vesicular release in the NTS astrocytes was blocked by virally driven expression of a dominant-negative SNARE protein in vivo. This increased baroreflex sensitivity in awake animals, which was also observed in anesthetized animals after topical application of the P2Y1 receptor antagonist MDS-2500 to the NTS. We hypothesize that NTS astrocytes respond to incoming afferent release of glutamate and this response is modulated by 5-HT originating from vagal afferents or other sources. ATP is then released, which acts on inhibitory interneurons via P2Y1 receptors and thus modulates the expression of cardiovascular reflexes.

Significance statement

Cardiorespiratory nuclei in the brainstem integrate cardiovascular sensory information to optimise tissue perfusion and blood gas concentrations. We describe experimental evidence that NTS astrocytes participate in setting the baroreflex sensitivity by release of ATP acting on P2Y1 receptors on inhibitory interneurons. Activation of astrocytes is partly under control of 5-HT co-released with glutamate from vagal afferents, which allows modulation of autonomic response to high frequency/duration of afferent stimulation by monitoring extra-synaptic 5-HT acting on glial 5-HT2A receptors. This could represent a signaling pathway that is activated under pathological conditions and is responsible for baroreflex impairment in conditions that result in astrogliosis, for example from systemic inflammatory response or chronic hypoxia/hypercapnia.
Variations in the coverage of biological soil crusts along a gradient of aridity in the center-west of argentina
Authors: Navas Romero A.L , Herrera Moratta M.A. , Vento B. , Rodriguez R.A. , Martínez Carretero E.E.
Published: August 2019

The biological soil crusts (biocrust) play a fundamental role in the arid and semiarid areas of South America. However, little attention has been paid to the distribution and coverage of them. In Argentina, studies about biocrust are still scarce. The goal of this contribution is to analyze the coverage of the biocrust and each of the functional component along a gradient of aridity in the center-west of Argentina. The gradient included three differentiated sites: semiarid, arid, and hyperarid sites. The coverage was recorded using the Point-quadrat method on 30 transects through a gradient consisting of three sites: semiarid, arid, and hyper-arid sites. The arid site was the system with the highest coverage of biocrust followed by the hyper-arid site. The semiarid site had the lowest values of coverage and showed significant differences among the three systems were found. Cyanobacteria’s dominate in the hyper-arid site. On the other hand, cyanobacteria and lichens were dominant in the arid site. The coverage of studied organisms showed variations in the semiarid site. These results support the idea that the coverage has a strong relationship with the features of the studied ecosystem and the environmental factors both at a mesoscale and a microscale in a determined community.
Cross-Species association statistics for genome-wide studies of host and parasite polymorphism data
Authors: Märkle Hanna , Tellier Aurélien , John Sona
Published: August 2019

Uncovering the genes governing host-parasite coevolutionary interactions is of importance for disease management. The increasing availability of host and parasite full genome-data allows for cross-species genome-wide association studies based on the genomic data of in-fected hosts and their associated parasite strains sampled from natural populations (i.e. natural co-GWAs). Such studies focus on searching for cross-species allelic associations between pairs of host and parasite SNPs. We aim to quantify the power of natural co-GWAs to pinpoint loci under coevolution with respect to the intrinsic complexities of coevolutionary systems, such as the genetic specificity of the interaction and the temporal allele frequency changes resulting from the interaction. Therefore, we develop the cross-species association (CSA) and the cross-species prevalence (CSP) indices, the latter additionally incorporating genomic data from uninfected hosts. To provide an assessment of the statistical power of these indices, we analytically derive their genome-wide False Discovery Rates (FDR) based on the neutral site-frequency spectrum of the host and the parasite population. Using two coevolutionary models, we investigate under which parameter regimes these indices pin-point the coevolving loci. Under trench warfare dynamics, CSA and CSP are very accurate in pinpointing the loci under coevolution, while under arms race dynamics the power is limited especially for gene-for-gene interactions. Furthermore, we reveal that the combination of both indices across time samples is an indicator for the specificity of the interaction. Our results provide novel insights into the power and biological interpretation of natural cross-species association studies.
Neural Anatomy and Optical Microscopy (NAOMi) Simulation for evaluating calcium imaging methods
Authors: Charles Adam S. , Song Alexander , Gauthier Jeff L. , Pillow Jonathan W. , Tank David W.
Published: August 2019

The past decade has seen a multitude of new in vivo functional imaging methodologies. However, the lack of ground-truth comparisons or evaluation metrics makes large-scale, systematic validation impossible. Here we provide a new framework for evaluating TPM methods via in silico Neural Anatomy and Optical Microscopy (NAOMi) simulation. Our computationally efficient model generates large anatomical volumes of mouse cortex, simulates neural activity, and incorporates optical propagation and scanning to create realistic calcium imaging datasets. We verify NAOMi simulations against in vivo two-photon recordings from mouse cortex. We leverage this access to in silico ground truth to perform direct comparisons between different segmentation algorithms and optical designs. We find modern segmentation algorithms extract strong neural time-courses comparable to estimation using oracle spatial information, but with an increase in the false positive rate. Comparison between optical setups demonstrate improved resilience to motion artifacts in sparsely labeled samples using Bessel beams, increased signal-to-noise ratio and cell-count using low numerical aperture Gaussian beams and nuclear GCaMP, and more uniform spatial sampling with temporal focusing versus multi-plane imaging. Overall, by leveraging the rich accumulated knowledge of neural anatomy and optical physics, we provide a powerful new tool to assess and develop important methods in neural imaging.
Nrf1 is endowed with a dominant tumor-repressing effect onto the Wnt/β-Catenin-dependent and -independent signaling networks in the human liver cancer
Authors: Chen Jiayu , Wang Meng , Ru Xufang , Xiang Yuancai , Ren Yonggang , Liu Xiping , Qiu Lu , Zhang Yiguo
Published: August 2019

Our previous work revealed that Nrf1α exerts a tumor-repressing effect because its genomic loss (to yieldNrf1α−/−) results in oncogenic activation of Nrf2 and target genes. Interestingly, β-catenin is concurrently activated by loss of Nrf1α in a way similar to β-catenin-driven liver tumor. However, a presumable relationship between Nrf1 and β-catenin is not as yet established. Here, we demonstrate that Nrf1 enhanced ubiquitination of β-catenin for targeting to proteasomal degradation. Conversely, knockdown of Nrf1 by its short-hairpin RNA (shNrf1) caused accumulation of β-catenin so as to translocate the nucleus, allowing activation of a subset of Wnt–β-catenin signaling responsive genes, which leads to the epithelial-mesenchymal transition (EMT) and related cellular processes. Such silencing of Nrf1 resulted in malgrowth of human hepatocellular carcinoma, along with malignant invasion and metastasis to the lung and liver in xenograft model mice. Further transcriptomic sequencing unraveled significant differences in the expression of both Wnt/β-catenin-dependent and -independent responsive genes implicated in the cell process, shape and behavior of the shNrf1-expressing tumor. Notably, we identified that β-catenin is not a target gene of Nrf1, but this CNC-bZIP factor contributes to differential or opposing expression of other critical genes, such asCDH1, Wnt5A, Wnt11A, FZD10, LEF, TCF4, SMAD4, MMP9, PTEN, PI3K, JUN and p53, each of which depends on the positioning of distinctcis-regulatory sequences (e.g., ARE and/or AP-1 binding sites) in the gene promoter contexts. In addition, altered expression profiles of some Wnt–β-catenin signaling proteins were context-dependent, as accompanied by decreased abundances of Nrf1 in the clinic human hepatomas with distinct differentiation. Together, these results corroborate the rationale that Nrf1 acts as abona fidedominant tumor-repressor, by its intrinsic inhibition of Wnt–β-catenin signaling and relevant independent networks in cancer development and malignant progression.
Taste quality representation in the human brain
Authors: Avery Jason A. , Liu Alexander G. , Ingeholm John E. , Riddell Cameron D. , Gotts Stephen J. , Martin Alex
Published: August 2019

In the mammalian brain, the insula is the primary cortical substrate involved in the perception of taste. Recent imaging studies in rodents have identified a gustotopic organization in the insula, whereby distinct insula regions are selectively responsive to one of the five basic tastes. However, numerous studies in monkeys have reported that gustatory cortical neurons are broadly-tuned to multiple tastes, and tastes are not represented in discrete spatial locations. Neuroimaging studies in humans have thus far been unable to discern between these two models, though this may be due to the relatively low spatial resolution employed in taste studies to date. In the present study, we examined the spatial representation of taste within the human brain using ultra-high resolution functional magnetic resonance imaging (MRI) at high magnetic field strength (7-Tesla). During scanning, participants tasted sweet, salty, sour and tasteless liquids, delivered via a custom-built MRI-compatible tastant-delivery system. Our univariate analyses revealed that all tastes (vs. tasteless) activated primary taste cortex within the bilateral dorsal mid-insula, but no brain region exhibited a consistent preference for any individual taste. However, our multivariate searchlight analyses were able to reliably decode the identity of distinct tastes within those mid-insula regions, as well as brain regions involved in affect and reward, such as the striatum, orbitofrontal cortex, and amygdala. These results suggest that taste quality is not represented topographically, but by a combinatorial spatial code, both within primary taste cortex as well as regions involved in processing the hedonic and aversive properties of taste.
Periaxonal and nodal plasticity modulate action potential conduction in the adult mouse brain
Authors: Cullen Carlie L , Pepper Renee E , Clutterbuck Mackenzie T , Pitman Kimberley A , Oorschot Viola , Auderset Loic , Tang Alexander D , Ramm Georg , Emery Ben , Rodger Jennifer , Jolivet Renaud B , Young Kaylene M
Published: August 2019

Central nervous system myelination increases action potential conduction velocity, however, it is unclear how myelination is coordinated to ensure the temporally precise arrival of action potentials, and facilitate information processing within cortical and associative circuits. Here, we show that mature myelin remains plastic in the adult mouse brain and can undergo subtle structural modifications to influence action potential arrival times. Repetitive transcranial magnetic stimulation and spatial learning, two stimuli that modify neuronal activity, alter the length of the nodes of Ranvier and the size of the periaxonal space within active brain regions. This change in the axon-glial configuration is independent of oligodendrogenesis and tunes conduction velocity to increase the synchronicity of action potential transit.
The wheat Seven in Absentia gene is associated with increases in biomass and yield in hot climates
Authors: Thomelin Pauline , Bonneau Julien , Brien Chris , Suchecki Radoslaw , Baumann Ute , Kalambettu Priyanka , Langridge Peter , Tricker Penny , Fleury Delphine
Published: August 2019

Wheat productivity is severely reduced by high temperatures. Breeding of heat tolerant cultivars can be achieved by identifying genes controlling physiological and agronomical traits with high temperature and using these to select superior genotypes, but no gene underlying genetic variation for heat tolerance has previously been described. We completed the positional cloning of qYDH.3BL, a quantitative trait locus (QTL) on bread wheat chromosome 3B associated with increased yield in hot and dry climates. The delimited genomic region contained 12 putative genes and a sequence variant in the promoter region of one gene - seven in absentia, TaSINA. This was associated with the QTL’s effects on early vigour, plant biomass and yield components in two distinct wheat populations grown under various growth conditions. Near isogenic lines carrying the positive allele at qYDH.3BL under-expressed TaSINA and had increased vigour and water use efficiency early in development, as well as increased biomass, grain number and grain weight following heat stress. A survey of worldwide distribution indicated that the positive allele became widespread from the 1950s through the CIMMYT wheat breeding programme but, to date, has been selected only in breeding programmes in Mexico and Australia.

Significance statement

Wheat is the world’s most widely grown crop and a staple of human diet. Even brief episodes of high temperature in the growing season cause severe yield reductions. Finding and deploying genes for heat stress tolerance in new varieties is a priority for food security with climate change. We narrowed a genetic locus to a small genomic region where genetic variation was present only in one gene that showed clear differences of expression and improved yield and physiology under stress in the populations. Using diagnostic markers to track the positive haplotype in nearly 750 accessions, we found many regions where the allele could be used in breeding programmes to increase wheat’s heat tolerance.
Structural basis for transcription activation by Crl through tethering of σS and RNA polymerase
Authors: Cartagena Alexis Jaramillo , Banta Amy B. , Sathyan Nikhil , Ross Wilma , Gourse Richard L. , Campbell Elizabeth A. , Darst Seth A.
Published: August 2019

In bacteria, a primary σ factor associates with the core RNA polymerase (RNAP) to control most transcription initiation, while alternative σ factors are used to coordinate expression of additional regulons in response to environmental conditions. Many alternative σ factors are negatively regulated by anti-σ factors. In Escherichia coli, Salmonella enterica, and many other γ-proteobacteria, the transcription factor Crl positively regulates the alternative σS regulon by promoting the association of σS with RNAP without interacting with promoter DNA. The molecular mechanism for Crl activity is unknown. Here, we determined a single-particle cryo-electron microscopy structure of Crl-σS-RNAP in an open promoter complex with a σS regulon promoter. In addition to previously predicted interactions between Crl and domain 2 of σS (σS), the structure, along with p-benzoylphenylalanine crosslinking, reveals that Crl interacts with a structural element of the RNAP β’ subunit we call the β’-clamp-toe (β’CT). Deletion of the β’CT decreases activation by Crl without affecting basal transcription, highlighting the functional importance of the Crl-β’CT interaction. We conclude that Crl activates σS-dependent transcription in part through stabilizing σS-RNAP by tethering σS and the β’CT. We propose that Crl, and other transcription activators that may use similar mechanisms, be designated σ-activators.

Significance Statement

In bacteria, multiple σ factors can bind to a common core RNA polymerase (RNAP) to alter global transcriptional programs in response to environmental stresses. Many γ-proteobacteria, including the pathogens Yersinia pestis, Vibrio cholera, Escherichia coli, and Salmonella typhimurium, encode Crl, a transcription factor that activates σS-dependent genes. Many of these genes are involved in processes important for infection, such as biofilm formation. We determined a high-resolution cryo-electron microscopy structure of a Crl-σS-RNAP transcription initiation complex. The structure, combined with biochemical experiments, shows that Crl stabilizes σS-RNAP by tethering σS directly to the RNAP.
Megaloneurite, a giant neurite of vasoactive intestinal peptide and nitric oxide synthase in the aged dog and identification by human sacral spinal cord
Authors: Li Yinhua , Hou Wei , Jia Yunge , Rao Chenxu , Wei Zichun , Xu Ximeng , Li Hang , Li Fuhong , Wang Xinghang , Zhang Tianyi , Sun Jingjing , Tan Huibing
Published: August 2019

Megaloneurite of NADPH diaphorase (NADPH-d) positivity is a new kind of aging-related neurodegeneration and also co-localized with vasoactive intestinal peptide (VIP) in the sacral spinal cord of aged dog and monkey. However, no immunocytochemistry of VIP was exclusively tested in the aged dog and no evidence has been reported in the aged human spinal cord. Aged dogs were used to examine the distribution of VIP immunopositivity in the sacral spinal cord. Immunocytochemistry of VIP and alpha-synuclein were also examined in the aged human spinal cord. The VIP immunopositivity in aged dog was reconfirmed our previous finding illustrated by immunofluorescent study. Megalogneurite was also identified by nitric oxide synthase (NOS) immunoreaction in aged dog. The VIP positive megaloneurites both in age dog and human were detected in dorsal root entry zoon, Lissauer’s tract, dorsal commissural nucleus and anterior commissural gray as well as in the lateral funiculus of the sacral spinal cord exclusive of other segments of spinal cord. Alpha-synuclein positivity was present mini-aggregation and Lewy body in the sacral spinal cord of aged human, that also occurred in the lumber, thoracic and cervical spinal cord. It was firstly tested that VIP megaloneurites occurred in the aged human sacral spinal cord, especially in the white matter. Megaloneurites identified by NADPH-d-VIP-NOS immunoreaction could implicate for the dysfunction of pelvic organs in the aged human being.
Novel quinolone resistance determinant, qepA8, in Shigella flexneri isolated in the United States, 2016
Authors: Webb Hattie E. , Tagg Kaitlin A. , Chen Jessica C. , Kim Justin , Lindsey Rebecca , Watkins Louise K. Francois , Karp Beth E. , Sugawara Yo , Folster Jason P.
Published: August 2019

A qepA8+ Shigella flexneri was cultured from the stool of a traveler returning from India and East Asia. This chromosomally encoded qepA variant, has a six-base insertion, and may have been mobilized as part of a complex IS1-mediated composite transposon including catA1, aadA1, and blaOXA-1. In laboratory E. coli, qepA8 alone only conferred decreased ciprofloxacin susceptibility; however, it may work in combination with additional mechanisms to confer clinical resistance.
DYNLRB1 is Essential for Dynein Mediated Transport and Neuronal Survival
Authors: Terenzio Marco , Di Pizio Agostina , Rishal Ida , Marvaldi Letizia , Di Matteo Pierluigi , Kawaguchi Riki , Coppola Giovanni , Schiavo Giampietro , Fisher Elizabeth M.C. , Fainzilber Mike
Published: August 2019

The cytoplasmic dynein motor complex transports essential signals and organelles from the cell periphery to perinuclear region, hence is critical for the survival and function of highly polarized cells such as neurons. Dynein Light Chain Roadblock-Type 1 (DYNLRB1) is thought to be an accessory subunit required for specific cargos, but here we show that it is essential for general dynein-mediated transport and sensory neuron survival. Homozygous Dynlrb1 null mice are not viable and die during early embryonic development. Furthermore, heterozygous or adult knockdown animals display reduced neuronal growth, and selective depletion of Dynlrb1 in proprioceptive neurons compromises their survival. Conditional depletion of Dynlrb1 in sensory neurons causes deficits in several signaling pathways, including β-catenin subcellular localization, and a severe impairment in the axonal transport of both lysosomes and retrograde signaling endosomes. Hence, DYNLRB1 is an essential component of the dynein complex.
VAC14 syndrome in two siblings with retinitis pigmentosa and neurodegeneration with brain iron accumulation
Authors: Lyon Gholson J. , Marchi Elaine , Ekstein Joseph , Meiner Vardiella , Hirsch Yoel , Scher Sholem , Yang Edward , De Vivo Darryl C. , Madrid Ricardo , Li Quan , Wang Kai , Haworth Andrea , Chilton Ilana , Chung Wendy K. , Velinov Milen
Published: August 2019

Whole-exome sequencing was used to identify the genetic etiology of a rapidly progressing neurological disease present in two of six siblings with early childhood onset of severe progressive spastic paraparesis and learning disabilities. A homozygous mutation (c.2005G>T, p, V669L) was found in VAC14, and the clinical phenotype is consistent with the recently described VAC14-related striatonigral degeneration, childhood-onset syndrome (SNDC) (MIM#617054). However, the phenotype includes a distinct clinical presentation of retinitis pigmentosa (RP), which has not previously been reported in association with VAC14 mutations. Brain magnetic resonance imaging (MRI) revealed abnormal magnetic susceptibility in the globus pallidus, which can be seen in neurodegeneration with brain iron accumulation (NBIA). RP is a group of inherited retinal diseases with phenotypic/genetic heterogeneity, and the pathophysiologic basis of RP is not completely understood but is thought to be due to a primary retinal photoreceptor cell degenerative process. Most cases of RP are seen in isolation (nonsyndromic); this is a report of RP in two siblings with VAC14-associated syndrome, and it is suggested that a connection between RP and VAC14-associated syndrome should be explored in future studies.
Stumped! The limits of global governance in a commercialized world of cricket
Authors: Siddiqui Javed , Yasmin Sofia , Humphrey Christopher
Published: August 2019

Purpose

The purpose of this paper is to analyse the shifting nature of governance reforms, both at global and national levels, in the increasingly commercialised game of cricket. The authors explore the inter-relationship and linkages between governance and commercialism, and in the process, question the contemporary reliance placed on governance as a generic counter-commercialist force and accountability aid.

Design/methodology/approach

The analysis is based on a comprehensive analysis of cricketing archives, newspapers and online media. The authors specifically utilise a range of review reports, governance and accounting information from annual reports and websites of the International Cricket Council (ICC) as well as different national cricket governing bodies (NCBs).

Findings

The paper vividly demonstrates the importance of recognising the specific significance of different cultural traditions and modes of organising – and not presuming a particular form of impact. The findings highlight that the adoption of a dominant market logic by cricket administrators has resulted in a shift in the balance of power in favour of non-western nations. India has emerged as the clear leader and driving force shaping the way cricket is globally governed. The consequences have been profound but not in terms of delivering, enhanced standards of transparency and accountability. Drawing on institutional theory, the paper argues that the scale of the Board of Cricket Control of India’s financial and operational control over the ICC has not only led to an increasingly commercialised game but engendered divergent and highly questionable standards of governance at the level of NCBs.

Originality/value

Unlike other global games, cricket has an imperialistic root, and has gone through the process of globalisation in relatively recent times. Also, the commercialisation of cricket has resulted in the global economic and power base shifting from the West to the East, giving us the opportunity to study the dynamics between commercialisation and governance in a quite different globalisation context that allows an assessment to be made of the culturally contingent nature of governance as a substantive organising force.
Operational risk management and customer complaints
Authors: Abdul Rahim Noor Fareen , Ahmed Essia Ries , Sarkawi Mohammad Nizam , Jaaffar Abdul Rahman , Shamsuddin Jauriyah
Published: August 2019

Purpose

The purpose of this paper is to examine the relationship between operational risk management and customer complaints. It also determines whether product complexity moderates the relationship between the operational risk management and customer complaints.

Design/methodology/approach

This study utilizes a quantitative method: quantitative data were collected using a questionnaire. The population of this study is 1,845 local conventional bank branches based in Malaysia.

Findings

The findings revealed that components of operational risk management, namely practice of hazard identification and formulation of implementation of risk control, have negative and significant relationships with customer complaints. Empirical evidence confirmed the moderating effects of product complexity on the relationship between operational risk management and customer complaints.

Originality/value

From the perspective of developing countries, the main contribution of this study is the elucidation of the effect of operational risk management on customer complaints in commercial banks in Malaysia. This study confirmed the usability of the resource-based view theory in the banking industry, as well as operational risk management as a bank resource.
An experience sampling approach to the workplace environment survey
Authors: Roskams Michael , Haynes Barry
Published: August 2019

Purpose

The purpose of this study is to pilot test the effectiveness of the experience sampling approach for measuring employee satisfaction with the workplace environment. Additionally, the authors also aimed to explore, which aspects of environmental comfort have the strongest impact on momentary well-being and productivity.

Design/methodology/approach

In total, 15 knowledge workers in an open-plan office environment were sent a brief survey (measuring environmental comfort, momentary well-being and perceived productivity) each day over an 11-day study period and provided 78 individual survey responses in total.

Findings

All but one of the measures on the survey had low test-retest reliability, indicating that employees’ experiences of environmental comfort varied significantly each time they completed the survey. Additionally, higher environmental comfort was associated with improved well-being and productivity.

Practical implications

The results suggest that an experience sampling approach to the workplace occupant survey is justified to better capture the temporal variability in experiences of environmental comfort. The results also suggest that improving environmental comfort, particularly by reducing the level of distractions, will enable employees to work more productively.

Originality/value

To the best of the authors’ knowledge, this is the first field study which has attempted to directly address limitations in traditional occupant surveys by using an experience sampling approach rather than a one-time-only questionnaire.
MHD free convection flow in an inclined square cavity filled with both nanofluids and gyrotactic microorganisms
Authors: Sheremet Mikhail , Grosan Teodor , Pop Ioan
Published: August 2019

Purpose

This paper aims to study the magnetohydrodynamic (MHD)-free convection flow in an inclined square cavity filled with both nanofluids and gyrotactic microorganism.

Design/methodology/approach

The benefits of adding motile microorganisms to the suspension include enhanced mass transfer, microscale mixing and anticipated improved stability of the nanofluid. The model includes equations expressing conservation of total mass, momentum, thermal energy, nanoparticles, microorganisms and oxygen. Physical mechanisms responsible for the slip velocity between the nanoparticles and the base fluid, such as Brownian motion and thermophoresis, are accounted for in the model.

Findings

It has been found that the Hartmann number suppresses the heat and mass transfer, while the cavity and magnetic field inclination angles characterize a non-monotonic behavior of the all considered parameters. A rise of the Hartmann number leads to a reduction of the influence rate of the magnetic field inclination angle.

Originality/value

The present results are original and new for the study of MHD-free convection flow in an inclined square cavity filled with both nanofluids and gyrotactic microorganisms.