bluuebunny/crossref_metadata_2025 huggingface dataset:
The clinical and functional effects ofTERTvariants in myelodysplastic syndrome
Authors: Reilly Christopher R. , Myllymäki Mikko , Redd Robert , Padmanaban Shilpa , Karunakaran Druha , Tesmer Valerie , Tsai Frederick D. , Gibson Christopher J. , Rana Huma Q. , Zhong Liang , Saber Wael , Spellman Stephen R. , Hu Zhen-Huan , Orr Esther H. , Chen Maxine M. , De Vivo Immaculata , Cutler Corey , Antin Joseph H. , Neuberg Donna , Garber Judy E. , Nandakumar Jayakrishnan , Agarwal Suneet , Lindsley R. Coleman
Published: February 2021

Germline pathogenicTERTvariants are associated with short telomeres and an increased risk of developing myelodysplastic syndrome (MDS) among patients with a telomere biology disorder. We identifiedTERTrare variants in 41 of 1514 MDS patients (2.7%) without a clinical diagnosis of telomere biology disorder who underwent allogeneic transplantation. Patients withTERTrare variants had shorter telomere length (p<0.001) and younger age at MDS diagnosis (52 vs. 59 years, p=0.03) than patients without aTERTrare variant. In multivariable analyses,TERTrare variants were associated with inferior overall survival (p=0.034) driven by an increased incidence of non-relapse mortality (NRM) (p=0.015). Death from a non-infectious pulmonary cause was more frequent among patients with aTERTrare variant. According to ACMG/AMP guidelines and Sherloc criteria, 39TERTrare variants were classified as VUS and one as likely pathogenic. Therefore, we cloned all rare missense variants and quantified their impact on telomere elongation in a cell-based assay. We found that 36 of 40 variants had severe or intermediate impairment in their capacity to elongate telomeres. Using a homology model of human TERT bound to the shelterin protein TPP1, we inferred that TERT rare variants disrupt domain-specific functions, including catalysis, protein-RNA interactions, and recruitment to telomeres. Our results indicate that the contribution ofTERTrare variants to MDS pathogenesis and NRM risk is underrecognized and routine screening forTERTrare variants in MDS patients regardless of age or clinical suspicion could identify clinically inapparent telomere biology disorders and improve transplant outcomes through risk-adapted approaches.
Abrupt remapping in human CA3/dentate gyrus signals resolution of memory interference
Authors: Guo Wanjia , Favila Serra E. , Kim Ghootae , Molitor Robert J. , Kuhl Brice A.
Published: February 2021

Remapping refers to a decorrelation of hippocampal representations of similar spatial environments. While it has been speculated that remapping may contribute to the resolution of episodic memory interference in humans, direct evidence is surprisingly limited. Here, we tested this idea using high-resolution, pattern-based fMRI analyses. We show that activity patterns in human CA3/dentate gyrus exhibit an abrupt, temporally-specific decorrelation of highly similar memory representations that is precisely coupled with behavioral expressions of successful learning. Strikingly, the magnitude of this learning-related decorrelation was predicted by the amount of pattern overlap during initial stages of learning, with greater initial overlap leading to stronger decorrelation. Finally, we show that remapped activity patterns carry relatively more information about learned episodic associations compared to competing associations, further validating the learning-related significance of remapping. Collectively, these findings establish a critical link between hippocampal remapping and episodic memory interference and provide novel insight into why remapping occurs.
Anti-diabetic effects ofHolarrhena antidysentricaextracts: Results from a Longitudinal Meta-analysis
Authors: Divya C. A. , Dhar Sujan K , Shantaram Manjula , Das Manjula
Published: February 2021

Background

Holarrhena antidysenterica(HA), a twining shrub belonging to the Apocynaceae family is found in tropical regions of Africa and over a large part of Asia including India, Philippines and Malayan Peninsula. In Indian traditional system of medicine, HA has been used to treat gastric ailments, for wound healing and also to improve glycaemic control. Glucose lowering activity of HA root, bark, seed, leaf and fruit extract in different parts of India as well as in Chinese traditional medicine is widely reported.

Purpose

In the meta-analysis reported in this article, we summarize glucose-lowering effects of HA extracts from different plant parts as reported in multiple studies involving animal models of diabetes. Our analysis helps to quantify the glucose-lowering effect of HA in comparison with standard diabetes drugs. The analysis also sheds light on differential efficacy levels of HA extracted from different plant parts.

Study design

The meta-analysis was carried out following PRISMA guidelines. Literature was searched to identify studies published between years 2011 to 2019 reporting glucose-lowering effects of HA extract on rodent models of diabetes.

Methods

Longitudinal meta-analysis was carried out on time-course data extracted from selected studies to calculate standardized mean change of glucose value from day 1 to days 7, 14 and 21 post-treatment by HA extract or standard anti-diabetic drug. Subgroup analysis was carried out for studies reporting effects of HA on leaf and seed extracts. Standardized mean difference in levels of cholesterol, triglycerides and serum total protein between treatment and control groups were also assessed.

Results

We shortlisted nine articles to be used for this meta-analysis. Summarized standardized mean changes of glucose value between day 1 and day 21 post-treatment indicated glucose-lowering effects of HA extracts to be marginally lower but comparable to that of standard anti-diabetic drugs like Glibenclamide or Sitagliptin. However, subgroup analysis revealed seed extracts of HA to be more potent than leaf extracts or even standard drugs. Effects of the extract on levels of cholesterol, triglyceride and serum total protein was also commensurate with its glucose-lowering property.

Conclusions

Our results, summarized over multiple studies, present a clear quantitative assessment of the anti-diabetic property of HA, in particular the seed extracts compared to standard anti-diabetic drugs. Further differential analysis of the seed extracts will be useful to arrive at a herbal formulation with superior anti-diabetic property and possibly lesser side effects than chemical entities.
Exploring the interspecific interactions and the metabolome of the soil isolateHylemonella gracilis
Authors: Tyc Olaf , Kulkarni Purva , Ossowicki Adam , Tracanna Vittorio , Medema Marnix H. , van Baarlen Peter , van IJcken W.F.J. , Verhoeven Koen J. F. , Garbeva Paolina
Published: February 2021

Microbial community analysis of aquatic environments showed that an important component of its microbial diversity consists of bacteria with cell sizes of ~0.1 μm. Such small bacteria can show genomic reductions and metabolic dependencies with other bacteria. However, so far no study investigated if such bacteria exist in terrestrial environments like e.g. soil.

Here, we isolated soil bacteria that passed through a 0.1 μm filter, by applying a novel isolation and culturing approach. The complete genome of one of the isolates was sequenced and the bacterium was identified asHylemonella gracilis. A set of co-culture assays with phylogenetically distant soil bacteria with different cell and genome sizes was performed. The co-culture assays revealed thatH. gracilisgrows better when interacting with other soil bacteria likePaenibacillussp. AD87and Serratia plymuthica. Transcriptomics and metabolomics showed thatH. graciliswas able to change gene expression, behavior, and biochemistry of the interacting bacteria without direct cell-cell contact.

Our study indicates that bacteria are present in the soil that can pass through a 0.1 μm filter. These bacteria may have been overlooked in previous research on soil microbial communities. Such small bacteria, exemplified here byH. gracilis,are able to induce transcriptional and metabolomic changes in other bacteria upon their interactions in soil. In vitro, the studied interspecific interactions allowed utilization of growth substrates that could not be utilized by monocultures, suggesting that biochemical interactions between substantially different sized soil bacteria may contribute to the symbiosis of soil bacterial communities.

Importance

Analysis of aquatic microbial communities revealed that parts of its diversity consist of bacteria with cell sizes of ~0.1 μm. Such bacteria can show genomic reductions and metabolic dependencies with other bacteria. So far, no study investigated if such bacteria exist in terrestrial environments e.g. soil. By applying a novel isolation method, we show that such bacteria also exist in soil. The isolated bacteria was identified asHylemonella gracilis.

Co-culture assays with phylogenetically different soil bacteria revealed thatH. gracilisgrows better when co-cultured with other soil bacteria. Transcriptomics and metabolomics showed thatH. graciliswas able to change gene expression, behavior, and biochemistry of the interacting bacteria without direct contact. Our study revealed that bacteria are present in soil that can pass through 0.1 μm filters. Such bacteria may have been overlooked in previous research on soil microbial communities and may contribute to the symbiosis of soil bacterial communities.
Neural markers for Musical Creativity in Jazz Improvisation and Classical Interpretation
Authors: Rahman Shama Sarwat , Christensen Kim , Jensen Henrik Jeldtoft , Vuust Peter , Bhattacharya Joydeep
Published: February 2021

Two main types of musical creativity in the western canon are improvisation and interpretation. With improvisation, the fundamental structure of the melody, chords, rhythm and tempo of a piece can be modified, while with interpretation, the focus is on the emotional dynamics. Here we characterise electrical brain activity from professional jazz and classical pianists, whilst they were engaged in these different creative tasks with musical excerpts from both genres. Multivariate EEG was recorded during two phases of each task, mental planning and actual performance. Subsequently neuronal activity patterns were source localised with standardised low resolution electromagnetic tomography (sLORETA). For each musical performance, we obtained both subjective (self-rated) and objective (blind, expert-rated) measures of musical creativity. Across both tasks and genre backgrounds, within the first and middle 4 second segments of the performance phase, for musical performances that were judged highly creative objectively by external expert music assessors, we observed an increased activation in the anterior cingulate and medial prefrontal cortex (Brodmann area, BA32), suggesting a maintenance of executive control, and integrating motoric and emotional communication during creativity. Across genre backgrounds, within the performance phase for the interpretation task compared to the improvisation task, there was an increased activity in the insula (BA 13), suggesting a convergent creative task from the linked goal-orientated conscious error-monitoring and audio-visual integration functions. Genre profession also gave rise to differences across phases; jazz pianists presented a decreased parietal (BA7) activity during improvisation tasks suggesting a role for defocussed attention and for classical pianists, both tasks were associated with occipitotemporal (BA 37) activity which is involved in semantic/ metaphorical processing suggesting a close adherence to the visual score. These 3 areas relate the cognitive demands of the creative musical task to the demands of the corresponding genre of music.

Highlights

EEG activity associated to musical creativity types: Improvisation and Interpretation

Increased activity in Insula (BA 13) for Interpretation suggest convergent creativity

Decreased Precuneus (BA7) activity for Improvisation suggest defocussed attention

Increased activity in medial prefrontal cortex (BA32) in highly creative performance
Extensive N4 Cytosine Methylation is Essential forMarchantiaSperm Function
Authors: Walker James , Zhang Jingyi , Liu Yalin , Vickers Martin , Dolan Liam , Nakajima Keiji , Feng Xiaoqi
Published: February 2021

4-methylcytosine (4mC) is an important DNA modification in prokaryotes, but its relevance, and even presence in eukaryotes have been mysterious. Here we show that spermatogenesis in the liverwortMarchantia polymorphainvolves two waves of extensive DNA methylation reprogramming. First, 5-methylcytosine (5mC), a well-known eukaryotic DNA modification, expands from transposons to the entire genome. Notably, the second wave installs 4mC throughout genic regions, covering over 50% of CG sites in sperm. 4mC is catalyzed by two novel methyltransferases (MpDN4MT1a and MpDN4MT1b) specifically expressed during late spermiogenesis. Deletion of MpDN4MT1seliminates 4mC, alters the sperm transcriptome, and produces sperm with swimming defects. Our results reveal extensive 4mC in a eukaryote and define a new family of eukaryotic methyltransferases, thereby expanding the repertoire of functional eukaryotic DNA modifications.
Coordinated changes in gene expression, H1 variant distribution and genome 3D conformation in response to H1 depletion
Authors: Serna-Pujol Núria , Salinas-Pena Mónica , Mugianesi Francesca , Le Dily François , Marti-Renom Marc A. , Jordan Albert
Published: February 2021

Up to seven members of the histone H1 family may contribute to chromatin compaction and its regulation in human somatic cells. In breast cancer cells, knock-down of multiple H1 variants deregulates many genes, promotes the appearance of genome-wide accessibility sites and triggers an interferon response via activation of heterochromatic repeats. However, how these changes in the expression profile relate to the re-distribution of H1 variants as well as to genome conformational changes have not been yet studied. Here, we combined ChIP-seq of five endogenous H1 variants with Chromosome Conformation Capture analysis in wild-type and H1 knock-down T47D cells. The results indicate that H1 variants coexist in the genome in two large groups depending on the local DNA GC content and that their distribution is robust with respect to multiple H1 depletion. Despite the small changes in H1 variants distribution, knock-down of H1 translated into more isolated but de-compacted chromatin structures at the scale of Topologically Associating Domains or TADs. Such changes in TAD structure correlated with a coordinated gene expression response of their resident genes. This is the first report describing simultaneous profiling of five endogenous H1 variants within a cell line and giving functional evidence of genome topology alterations upon H1 depletion in human cancer cells.
Dopamine modulates visual threat processing in the superior colliculus via D2 receptors
Authors: Montardy Quentin , Zhou Zheng , Li Lei , Yang Qingning , Lei Zhuogui , Feng Xiaolong , Chen Shanping , Shi Qianqian , Zhang Huiqi , Chen Shuran , Zhang Zhijian , Zhao Binghao , Xu Fuqiang , Lu Zhonghua , Wang Liping
Published: February 2021

Dopamine (DA) system is intriguing in the aspect that distinct, typically opposing physiological functions are mediated by D1 dopamine receptors (Drd1) and D2 dopamine receptors (Drd2). Both Drd1+ and Drd2+ neurons were identified in superior colliculus (SC), a visuomotor integration center known for its role in defensive behaviors to visual threats. We hypothesized that Drd1+ and Drd2+ neurons in the SC may play a role in promoting instinctive defensive responses.

Optogenetic activation of Drd2+ neurons, but not Drd1+ neurons, in the SC triggered strong defensive behaviors. Chemogenetic inhibition of SC Drd2+ neurons decreased looming-induced defensive behavior, suggesting involvement of SC Drd2+ neurons in defensive responses. To further confirm this functional role of Drd2 receptors, pretreatment with the Drd2+ agonist quinpirole in the SC impaired looming-evoked defensive responses, suggesting an essential role of Drd2 receptors in the regulation of innate defensive behavior. Inputs and outputs of SC Drd2+ neurons were investigated using viral tracing: SC Drd2+ neurons mainly receive moderate inputs from the Locus Coeruleus (LC), whilst we did not find any incoming projections from other dopaminergic structures. Our results suggest a sophisticated regulatory role of DA and its receptor system in innate defensive behavior.
Sterile Inflammation Alters Neutrophil Kinetics in Mice
Authors: Singh Alakesh , Jothiprakasam Thiruvickraman , Raghavan Jayashree V. , Jhunjhunwala Siddharth
Published: February 2021

Neutrophils play a crucial role in establishing inflammation in response to an infection or injury, but their production rates, as well as blood and tissue residence times, remain poorly characterized under these conditions. Herein, using a biomaterial implant model to establish inflammation followed byin vivotracking of newly formed neutrophils, we determine neutrophil kinetics under inflammatory conditions. To obtain quantifiable information from our experimental observations, we develop an ordinary differential equation-based mathematical model to extract kinetic parameters. Our data show that in the presence of inflammation resulting in emergency granulopoiesis-like conditions, neutrophil maturation time in the bone marrow and half-life in the blood reduces by about 40%, compared to non-inflammatory conditions. Additionally, neutrophil residence time at the inflammatory site increases by two-fold. Together, these data improve our understanding of neutrophil kinetics under inflammatory conditions, which could pave the way for therapies that focus on modulating in vivo neutrophil dynamics.
Life histories as mosaics: plastic and genetic components differ among traits that underpin life-history strategies
Authors: Felmy Anja , Reznick David N. , Travis Joseph , Potter Tomos , Coulson Tim
Published: February 2021

Life-history variation reflects phenotypic variation across suites of traits. Differences among life-history strategies result from genetic differentiation, phenotypic plasticity, and genotype-by-environment interactions. If the relative strength and direction of these components differed among traits underlying a strategy, life histories might not evolve as a cohesive unit.

We tested this hypothesis on the high- and low-predation ecotypes of Trinidadian guppies, defined by distinct life-history strategies. Using common garden experiments, we assessed how strongly 36 traits were determined by ancestral habitat (i.e., ecotype) or food availability, a key environmental difference between ecotypes. Our dataset was large (1178 individuals) and included six putatively independent origins of the derived ecotype.

Traits could be confidently assigned to four groups, defined by highly significant effects of only food (13 traits), only habitat (6), both (6), or neither (11), revealing substantial variation among traits in levels of genetic and environmental control. Ecotype-food (i.e., genotype-by-environment) interactions were negligible. The directions of plastic and genetic effects were usually aligned.

This suggests that life histories are mosaics with unequal rates of phenotypic and evolutionary change. Broadly speaking of “life-history evolution” masks a complex interplay of genes and environment on the multiple traits that underpin life-history strategies.
Kinetics and topology of DNA associated with circulating extracellular vesicles released during exercise
Authors: Neuberger Elmo W. I. , Hillen Barlo , Mayr Katharina , Simon Perikles , Krämer-Albers Eva-Maria , Brahmer Alexandra
Published: February 2021

Although it is widely accepted that cancer derived extracellular vesicles (EVs) carry DNA cargo, the association of cell-free circulating DNA (cfDNA) and EVs in plasma of healthy humans remains elusive. Using a physiological exercise model, where EVs and cfDNA are synchronously released, we aimed to characterize the kinetics and localization of DNA associated with EVs. EVs were separated from human plasma using size exclusion chromatography or immuno-affinity capture for CD9+, CD63+, and CD81+EVs. DNA was quantified with an ultra-sensitive qPCR assay targeting repetitive LINE elements, with or without DNase digestion. This model shows that a minute part of circulating cell-free DNA is associated with EVs. During rest and following exercise, only 0.12 % of the total cfDNA occurs in association with CD9+/CD63+/CD81+EVs. DNase digestion experiments indicate that the largest part of EV associated DNA is sensitive to DNase digestion and only ~20 % are protected within the lumen of the separated EVs. A single bout of running or cycling exercise increases the levels of EVs, cfDNA, and EV associated DNA. While EV surface DNA is increasing, DNAse-resistant DNA remains at resting levels, indicating that EVs released during exercise (ExerVs) do not contain DNA. Consequently, DNA is largely associated with the outer surface of circulating EVs. ExerVs recruit cfDNA to their corona, but do not carry DNA in their lumen.
Sexually antagonistic evolution of mitochondrial and nuclear linkage
Authors: Radzvilavicius Arunas , Layh Sean , Hall Matthew D. , Dowling Damian K. , Johnston Iain G.
Published: February 2021

Across eukaryotes, genes encoding bioenergetic machinery are located in both mitochondrial and nuclear DNA, and incompatibilities between the two genomes can be devastating. Mitochondria are often inherited maternally, and theory predicts sex-specific fitness effects of mitochondrial mutational diversity. Yet how evolution acts on linkage patterns between mitochondrial and nuclear genomes is poorly understood. Using novel mito-nuclear population genetic models, we show that the interplay between nuclear and mitochondrial genes maintains mitochondrial haplotype diversity within populations, and it selects both for sex-independent segregation of mitochondrion-interacting genes and for paternal leakage. These effects of genetic linkage evolution can eliminate male-harming fitness effects of mtDNA mutational diversity. With maternal mitochondrial inheritance, females maintain a tight mitochondrial-nuclear match, but males accumulate mismatch mutations because of the weak statistical associations between the two genomic components. Sex-independent segregation of mitochondria-interacting loci improves the mito-nuclear match. In a sexually antagonistic evolutionary process, male nuclear alleles evolve to increase the rate of recombination, while females evolve to suppress it. Paternal leakage of mitochondria can evolve as an alternative mechanism to improve the mito-nuclear linkage. Our modelling framework provides an evolutionary explanation for the observed paucity of mitochondrion-interacting genes on mammalian sex chromosomes and for paternal leakage in protists, plants, fungi, and some animals.
Fighting over defence chemicals disrupts mating behaviour
Authors: Paul Sarah Catherine , Müller Caroline
Published: February 2021

Studies on intraspecific contest behaviour predominantly focus on contests between individuals of the same sex, however contest behaviour is also expected to occur between individuals of the opposite sex including possible mates. Here we investigate potential trade-offs between mating and fighting behaviour in the turnip sawfly (Athalia rosae). Adults of this species collect chemical defence compounds (clerodanoids) directly from plants but also indirectly by nibbling on conspecifics that have already obtained clerodanoids themselves, a highly aggressive behavioural interaction. An A. rosae individual without clerodanoids may therefore be the potential mate or attacker of an individual of the opposite sex that has gained clerodanoids. We paired males and females with or without clerodanoid access and manipulated body mass differences between the sexes via the early life starvation of females. We show that asymmetrical clerodanoid acquisition between male-female pairs causes an increase in agonistic nibbling behaviour, irrespective of sex. Moreover, fighting over clerodanoids disrupted mating behaviour, and the frequency of aggressive nibbling behaviour in these pairs was determined by the comparative body mass of the attacking individual. Our study highlights the vital importance of investigating agonistic intersex interactions not only over mating but also over resources.
Parameter estimation for correlated Ornstein-Uhlenbeck time-series
Authors: Strey Helmut H. , Kumar Rajat , Mujica-Parodi Lilianne
Published: February 2021

In this article, we develop a Maximum likelihood (ML) approach to estimate parameters from correlated time traces that originate from coupled Ornstein-Uhlenbeck processes. The most common technique to characterize the correlation between time-series is to calculate the Pearson correlation coefficient. Here we show that for time series with memory (or a characteristic relaxation time), our method gives more reliable results, but also results in coupling coefficients and their uncertainties given the data. We investigate how these uncertainties depend on the number of samples, the relaxation times and sampling time. To validate our analytic results, we performed simulations over a wide range of correlation coefficients both using our maximum likelihood solutions and Markov-Chain Monte-Carlo (MCMC) simulations. We found that both ML and MCMC result in the same parameter estimations. We also found that when analyzing the same data, the ML and MCMC uncertainties are strongly correlated, while ML underestimates the uncertainties by a factor of 1.5 to 3 over a large range of parameters. For large datasets, we can therfore use the less computationally expensive maximum likelihood method to run over the whole dataset, and then we can use MCMC on a few samples to determine the factor by which the ML method underestimates the uncertainties. To illustrate the application of our method, we apply it to time series of brain activation using fMRI measurements of the human default mode network. We show that our method significantly improves the interpretation of multi-subject measurements of correlations between brain regions by providing parameter confidence intervals for individual measurements, which allows for distinguishing between the variance from differences between subjects from variance due to measurement error.
StrainFLAIR: Strain-level profiling of metagenomic samples using variation graphs
Authors: Da Silva Kévin , Pons Nicolas , Berland Magali , Oñate Florian Plaza , Almeida Mathieu , Peterlongo Pierre
Published: February 2021

Current studies are shifting from the use of single linear references to representation of multiple genomes organised in pangenome graphs or variation graphs. Meanwhile, in metagenomic samples, resolving strain-level abundances is a major step in microbiome studies, as associations between strain variants and phenotype are of great interest for diagnostic and therapeutic purposes.

We developedStrainFLAIRwith the aim of showing the feasibility of using variation graphs for indexing highly similar genomic sequences up to the strain level, and for characterizing a set of unknown sequenced genomes by querying this graph.

On simulated data composed of mixtures of strains from the same bacterial speciesEscherichia coli, results show thatStrainFLAIRwas able to distinguish and estimate the abundances of close strains, as well as to highlight the presence of a new strain close to a referenced one and to estimate its abundance. On a real dataset composed of a mix of several bacterial species and several strains for the same species, results show that in a more complex configurationStrainFLAIRcorrectly estimates the abundance of each strain. Hence, results demonstrated how graph representation of multiple close genomes can be used as a reference to characterize a sample at the strain level.

Availability

http://github.com/kevsilva/StrainFLAIR
Programmed ER fragmentation drives selective ER inheritance and degradation in budding yeast meiosis
Authors: Otto George M. , Cheunkarndee Tia , Leslie Jessica M. , Brar Gloria A.
Published: February 2021

The endoplasmic reticulum (ER) is a membrane-bound organelle with diverse, essential functions that rely on the maintenance of membrane shape and distribution within cells. ER structure and function are remodeled in response to changes in cellular demand, such as the presence of external stressors or the onset of cell differentiation, but mechanisms controlling ER remodeling during cell differentiation are not well understood. Here, we describe a series of developmentally regulated changes in ER morphology and composition during budding yeast meiosis, a conserved differentiation program that gives rise to gametes. During meiosis, the cortical ER undergoes fragmentation before collapsing away from the plasma membrane at anaphase II. This programmed collapse depends on the meiotic transcription factor Ndt80, conserved ER membrane structuring proteins Lnp1 and reticulons, and the actin cytoskeleton. A subset of ER is retained at the mother cell plasma membrane and excluded from gamete cells via the action of ER-plasma membrane tethering proteins. ER remodeling is coupled to ER degradation by selective autophagy, which is regulated by the developmentally timed expression of the autophagy receptor Atg40. Autophagy relies on ER collapse, as artificially targeting ER proteins to the cortically retained ER pool prevents their degradation. Thus, developmentally programmed changes in ER morphology determine the selective degradation or inheritance of ER subdomains by gametes.
An improved ChEC-seq method accurately maps the genome-wide binding of transcription coactivators and sequence-specific transcription factors
Authors: Donczew Rafal , Lalou Amélia , Devys Didier , Tora Laszlo , Hahn Steven
Published: February 2021

Mittal and colleagues have raised questions about mapping transcription factor locations on DNA using the MNase-based ChEC-seq method (Mittal et al., 2021). Partly due to this concern, we modified the experimental conditions of the MNase cleavage step and subsequent computational analyses, resulting in more stringent conditions for mapping protein-DNA interactions (Donczew et al., 2020). The revised method (dx.doi.org/10.17504/protocols.io.bizgkf3w) answers questions raised by Mittal et al. and, without changing earlier conclusions, identified widespread promoter binding of the transcription coactivators TFIID and SAGA at active genes. The revised method is also suitable for accurately mapping the genome-wide locations of DNA sequence-specific transcription factors.
Single-cell Visualization and Quantification of Trace Metals in Chlamydomonas Lysosome-Related Organelles
Authors: Schmollinger Stefan , Chen Si , Strenkert Daniela , Hui Colleen , Ralle Martina , Merchant Sabeeha S.
Published: February 2021

The acidocalcisome is an acidic organelle in the cytosol of eukaryotes, defined by its low pH and high calcium and polyphosphate content. It is visualized as an electron-dense object by transmission electron microscopy (TEM) or described with mass-spectrometry (MS)-based imaging techniques or multimodal X-ray fluorescence microscopy (XFM) based on its unique elemental composition. Compared to MS-based imaging techniques, XFM offers the advantage of absolute quantification of trace metal content, since sectioning of the cell is not required and metabolic states can be preserved rapidly by either vitrification or chemical fixation. We employed XFM inChlamydomonas reinhardtii, to determine single-cell and organelle trace metal quotas within algal cells in situations of trace metal over-accumulation (Fe, Cu). We found up to 70% of the cellular Cu and 80% of Fe sequestered in acidocalcisomes in these conditions, and identified two distinct populations of acidocalcisomes, defined by their unique trace elemental makeup. We utilized thevtc1mutant, defective in polyphosphate synthesis and failing to accumulate Ca to show that Fe sequestration is not dependent on either. Finally, quantitation of the Fe and Cu contents of individual cells and compartments via XFM, over a range of cellular metal quotas created by nutritional and genetic perturbations, indicated excellent correlation with bulk data from corresponding cell cultures, establishing a framework to distinguish the nutritional status of single cells.

Significance statement

Transition metals are of crucial importance for primary productivity; their scarcity limits crop yield in agriculture and carbon sequestration at global scale. Copper (Cu), iron (Fe) and manganese (Mn) are among the most important trace elements that enable the redox chemistry in oxygenic photosynthesis. The single-celled, eukaryotic green algaChlamydomonas reinhardtiiis a choice experimental system for studying trace metal homeostasis in the context of phototrophy, offering all the advantages of a classical microbial system with a well-characterized photosystem and trace metal metabolism machinery of relevance to plants. This project identifies and differentiates different trace metal storage sites in Chlamydomonas and uncovers the dynamics of trace metal storage and mobilization in situations of fluctuating resources.
Quantifying habitat and landscape effects on composition and structure of plant-pollinator networks in the US Northern Great Plains
Authors: Vilella-Arnizaut Isabela B. , Nottebrock Henning , Fenster Charles B.
Published: February 2021

Community structure contributes to ecosystem persistence and stability. To understand the mechanisms underlying pollination and community stability of natural areas in a human influenced landscape, a better understanding of the interaction patterns between plants and pollinators in disturbed landscapes is needed. The Northern Great Plains still retain extensive tracts of remnant temperate grassland habitat within a matrix of varying land-uses. We used a network-based approach to quantify how temperate grassland attributes and landscape heterogeneity influence plant-pollinator community structure in natural habitats. We also quantified pollinator diversity and floral diversity to assess the functional role of temperate grassland attributes and the surrounding landscape on the composition of the plant-pollinator communities in natural habitats. We found that the amount of local nectar sugar and increased proportions of certain land-uses contribute to pollinator diversity that in turn influences the structure of interactions between plants and pollinators. Understanding the factors contributing to plant-pollinator network structure can guide management decisions to support resilient plant-pollinator communities and conserve the stability of pollination services.
Melanoma cells adopt features of both mesenchymal and amoeboid migration within confining channels
Authors: Gabbireddy Sairisheel R. , Chung Aram J. , Logue Jeremy S.
Published: February 2021

For metastasis to occur, cancer cells must traverse a range of tissue environments. In part, this is accomplished by cells adjusting their migration mode to one that is best suited to the environment. Melanoma cells have been shown to be particularly plastic, frequently using both mesenchymal and amoeboid (bleb-based) modes of migration. It has been demonstrated that 2D confinement will promote the transition from mesenchymal to bleb-based migration. However, if melanoma cells similarly transition to bleb-based migration in response to 3D confinement, such as within narrow channels, is unknown. Here, using micro-fabricated channels, we demonstrate that melanoma cells adopt features of both mesenchymal and bleb-based migration. In narrow (8 μm; height and width) channels coated with fibronectin, ~50% of melanoma cells were found to use either mesenchymal or bleb-based migration modes. In contrast, the inhibition of Src family kinases or coating channels with BSA, completely eliminated any features of mesenchymal migration. Detailed comparisons of migration parameters revealed that blebbing cells, particularly in the absence of adhesions, were faster than mesenchymal cells. In contrast to what has been previously shown under conditions of 2D confinement, pharmacologically inhibiting Arp2/3 promoted a fast filopodial-based mode of migration. Accordingly, we report that melanoma cells adopt a unique range of phenotypes under conditions of 3D confinement.
Adaptive sensor fusion labeling framework for hand pose recognition in robot teleoperation
Authors: Qi Wen , Liu Xiaorui , Zhang Longbin , Wu Lunan , Zang Wenchuan , Su Hang
Published: February 2021

Purpose

The purpose of this paper is to mainly center on the touchless interaction between humans and robots in the real world. The accuracy of hand pose identification and stable operation in a non-stationary environment is the main challenge, especially in multiple sensors conditions. To guarantee the human-machine interaction system’s performance with a high recognition rate and lower computational time, an adaptive sensor fusion labeling framework should be considered in surgery robot teleoperation.

Design/methodology/approach

In this paper, a hand pose estimation model is proposed consisting of automatic labeling and classified based on a deep convolutional neural networks (DCNN) structure. Subsequently, an adaptive sensor fusion methodology is proposed for hand pose estimation with two leap motions. The sensor fusion system is implemented to process depth data and electromyography signals capturing from Myo Armband and leap motion, respectively. The developed adaptive methodology can perform stable and continuous hand position estimation even when a single sensor is unable to detect a hand.

Findings

The proposed adaptive sensor fusion method is verified with various experiments in six degrees of freedom in space. The results showed that the clustering model acquires the highest clustering accuracy (96.31%) than other methods, which can be regarded as real gestures. Moreover, the DCNN classifier gets the highest performance (88.47% accuracy and lowest computational time) than other methods.

Originality/value

This study can provide theoretical and engineering guidance for hand pose recognition in surgery robot teleoperation and design a new deep learning model for accuracy enhancement.
Spirituality, happiness and auditors' commitment: an interbeing perspective
Authors: Efferin Sujoko , Hutomo Christopher Christian
Published: February 2021

Purpose

This study attempts to explore the meaning and implication of spirituality in an accounting firm by using a Buddhist perspective of interbeing. It explains how the happiness of individuals (auditors, partners, clients and auditor family members); organisational performance and growth and auditors' commitment are interconnected and impermanent.

Design/methodology/approach

This study employed an interpretive case study in an Indonesian accounting firm. The researchers explored the collective and individual feelings, thoughts, actions and experiences of the firm's actors. The data collection methods were interviews, participant observations and documentary analysis.

Findings

Leadership plays a major role in cultivating spirituality in an accounting firm. The spirituality increases auditors' commitment, (conditional) happiness and performance resulting in client satisfaction and the firm's growth. From an interbeing perspective, partners, auditors and clients are interconnected and impermanent. A firm's growth creates a growing sense of unhappiness due to the diminishing of auditors' comfort zone. Spirituality in the workplace can only engender conditional happiness and organisational commitment that offset the importance of material rewards and career prospects. To reach ultimate (unconditional) happiness, one requires a continuous spiritual development.

Research limitations/implications

The insights gained from this study need enrichment from cases in different contexts, e.g. multinational firms with members from different countries and cultures.

Originality/value

This study develops the discourse of emancipation in the accounting literature by taking into account spirituality and happiness.
Management controls and crisis: evidence from the banking sector
Authors: Rikhardsson Pall , Rohde Carsten , Christensen Leif , Batt Catherine E.
Published: February 2021

Purpose

This paper investigates the use of management controls when environmental uncertainty and hostility increase abruptly. Specifically, it explores this in the context of the 2008 financial crisis in six banks located in two countries.

Design/methodology/approach

The paper is based on 26 qualitative interviews with selected managers employed by the six banks. Eight interview guides were developed based on the typology of controls in Malmi and Brown (2008). Respondents explained which changes in management controls occurred after the crisis.

Findings

Both organic and mechanistic management controls were mobilized at the same time to deal with the change. The use of controls played three main roles: (1) guide and control behavior, (2) change internal and external perceptions and (3) discharge accountability. Finally, control use during a crisis evolves as individual managers design and implement controls. There is no “grand design” rationally guiding the design of the overall system of controls.

Originality/value

The use of management controls in dealing with an increase in uncertainty and hostility cannot be labeled either organic or mechanistic, but will depend on the specific type of change in environmental characteristics. Management controls evolve by interaction with outside actors, as well as internal techniques.
Pathway to care in co-occurring disorder and substance use disorder: an exploratory, cross-sectional study from India
Authors: Tripathi Richa , Singh Shalini , Sarkar Siddharth , Lal Rakesh , Balhara Yatan Pal Singh
Published: February 2021

Purpose

There is a paucity of comparative literature on pathway to care among patients with co-occurring disorders and those with only substance use disorders. This paper aims to compare the pathways to care among patients with co-occurring disorder and those with only substance use disorders.

Design/methodology/approach

A cross-sectional observational study was carried out on male treatment seekers at a tertiary care substance use disorder treatment center in India. Participants were recruited in two groups, those with co-occurring psychiatric and substance use disorders and those with only substance use disorders. The two groups were matched for age and socio-economic status.

Findings

A total of 189 subjects with co-occurring psychiatric and substance use disorders and 197 subjects with substance use disorders only were recruited. Psychiatric services were the most common first point of care. However, a larger proportion of the subjects in the co-occurring disorder group received the first care from faith healers, while a greater proportion received first care from the therapeutic communities in substance use disorder only group. Initial care was sought mostly following suggestion from the family members in both the groups. The time to treatment for substance use disorders did not differ between the two groups, though the treatment seeking for substance use disorder was more delayed than that of psychiatric disorder in the co-occurring disorder group.

Research limitations/implications

The findings shed light on the pathway of care followed in India and is a matter of further research.

Practical implications

Expansion of services and dissemination of information about psychiatric disorders and substance use disorders can provide timely care to patients with substance use disorders and co-occurring disorders.

Social implications

The findings have a social implication as well. More awareness is needed currently in India for timely treatment of dual disorders.

Originality/value

The paper is an original research by the authors. The data were collected from the participants who reported to the dual diagnosis clinic. The findings are important as they tell us about the current understanding of dual diagnosis by the general public.
Research on influencing factors of fuel tank flammability exposure time for transport aircraft
Authors: Ruihua Zhang , Liu Weihua , Liu Wenyi
Published: February 2021

Purpose

The assessment of fuel tank flammability exposure time for transport aircraft is one of the indispensable links in the airworthiness certification process. According to published literature, many factors can affect the flammability exposure time, while systematic analysis and calculations addressing these factors are in shortage.

Design/methodology/approach

Based on the requirements for airworthiness certification of domestic large aircraft, the fuel tank flammability exposure time of transport aircraft is calculated with the Monte Carlo evaluation model specified by Federal Aviation Administration. Meanwhile, the influence of each input parameter on the flammability exposure time is obtained by taking user input parameters in the model as independent variables and freezing other factors at the same time. The significance degree of the influence of each factor is discussed by the orthogonal test method. Subsequently, the interaction between the input parameters is studied by response surface method, and a multiple linear regression method is used to establish the functional relationship between the flammability exposure time and the influence parameters.

Findings

Research studies show that among the many factors that affect the flammability exposure time, the cruising Mach number, the equilibrium temperature difference and the maximum range are more significant and much attention should be paid to in the airworthiness certification; although there are interactions among various factors, they have different influence on the flammability exposure time, among which the interactions between maximum range and equilibrium temperature difference are the most significant compared with others; established by applying multiple linear regression equation and based on the test data of response surface method, the functional relationship between flammability exposure time and influence parameters is of sufficient reliability and can be used for preliminary prediction of fuel tank flammability exposure time for transport aircraft.

Originality/value

The research achievements of this paper can provide much useful reference for the certification of domestic large aircraft.
Glasgow anxiety scale for people with an intellectual disability (GAS-ID): validation for Spanish population
Authors: Núñez-Polo Mercedes Hernández , Alonso-Rodríguez María-Concepción , Dolado Ana , Ayuso-Mateos José-Luis , Martorell Almudena
Published: February 2021

Purpose

Anxiety disorder is a common mental health problem in people with intellectual disabilities. Although this affects their quality of life, in Spain, there are no validated tools to evaluate the symptomatology of anxiety in people with intellectual disabilities. The aim of this study is to validate the Glasgow Anxiety Scale for people with an intellectual disability (GAS-ID) in the Spanish population.

Design/methodology/approach

The Spanish version of the GAS-ID was produced by back translation and was administered to 120 adults with intellectual disabilities. The psychometric analyses included internal consistency using the Cronbach’s alpha coefficient, inter-rater and test-retest reliability were determined using intra class correlation and Pearson correlation coefficients and, finally, factor analysis with Varimax rotation to confirm the construct validity of the questionnaire.

Findings

Cronbach’s alpha was 0.86 for the overall questionnaire. The intraclass correlation coefficient showed a good level of agreement in both test-retest (0.90) and inter-rater (0.91) analysis and the Pearson correlation showed a good significance in all dimensions and in the total scale. Varimax rotation factor analysis revealed four well-defined factors.

Originality/value

The GAS-ID is a feasible and reliable instrument for assessing anxiety symptoms in adults with mild and moderate intellectual disabilities, offering better diagnoses and therefore a more accurate treatment for the Spanish population with intellectual disabilities.