bluuebunny/crossref_metadata_2025 huggingface dataset:
Damaraland mole-rats are not obligate cooperative breeders
Authors: Thorley Jack , Bensch Hanna M. , Finn Kyle , Clutton-Brock Tim , Zöttl Markus
Published: December 2021

Damaraland mole-rats (Fukomys damarensis) are usually viewed as a eusocial or obligate cooperative breeder in which successful reproduction is dependent on help from closely related group members. However, because longitudinal studies of mole-rats in their natural environment are uncommon, the extent to which successful reproduction by breeders relies on assistance from other group members is unclear, and for non-breeders, the immediate and delayed fitness consequences of staying and helping are poorly understood. Using data from a 7-year field study of marked individuals, we investigate whether increasing group size confers reproductive and survival benefits to breeders and non-breeders, and explore the different routes through which individuals acquire breeding positions. We show that solitary natal dispersal was the most common route to breeding for both sexes and that the inheritance of dominant breeding positions was uncommon in both sexes. After dispersing, females typically settled alone in new burrow systems where they enjoyed high survival rates and remained in good body condition - often for several years - before being joined by males. In contrast to most obligately cooperative species, pairs of potential breeders reproduced successfully without helpers and experimentally formed pairs had the same reproductive success as larger established groups. Though larger breeding groups recruited slightly more pups on average, our data suggest that neither survival nor reproduction depend on the presence of non-breeding helpers, indicating that Damaraland mole-rats are not obligate cooperative breeders. We suggest that extended philopatry and group living in Damaraland mole-rats have evolved because of the high costs and constraints of dispersal rather than because of strong indirect benefits accrued through cooperative behaviour and that similarities between their breeding systems and those of obligatorily eusocial insects have been over-emphasized.

Significance Statement

The social mole-rats are often considered eusocial mammals in which successful reproduction depends on assistance from non-breeding helpers. In this study we show that in wild Damaraland mole-rats, the presence of non-breeders is associated with both costs and benefits and that nascent breeding pairs show high reproductive success despite the lack of non-breeding helpers. These findings indicate that Damaraland mole-rats are not obligate cooperative breeders and suggest that similarities between their breeding systems and those of obligatorily eusocial insects have been over-emphasized.
Mapping of the autophagosomal degradome identifies IL-7Rα as key cargo in proliferating CD4+ T-cells
Authors: Zhou Dingxi , Borsa Mariana , Puleston Daniel J. , Zellner Susanne , Capera Jesusa , Sanderson Sharon , Jostins Luke , Behrends Christian , Alsaleh Ghada , Simon Anna Katharina
Published: December 2021

CD4+ T cells orchestrate both humoral and cytotoxic immune responses. While it is known that CD4+ T cell proliferation relies on autophagy, direct identification of the autophagosomal cargo involved is still missing. Here, we created a transgenic mouse model, which, for the first time, enables us to directly map the proteinaceous content of autophagosomes in any primary cell by LC3 proximity labelling. IL-7Rα, a cytokine receptor mostly found in naïve and memory T cells, was reproducibly detected in autophagosomes of activated CD4+ T cells. Consistently, CD4+ T cells lacking autophagy showed increased IL-7Rα surface expression, while no defect in internalisation was observed. Mechanistically, excessive surface IL-7Rα sequestrates the common gamma chain, impairing the IL-2R assembly and downstream signalling crucial for T cell proliferation. This study provides proof-of-principle that key autophagy substrates can be reliably identified with this model to help mechanistically unravel autophagy’s contribution to healthy physiology and disease.
Microbiome Analysis of Gut Bacterial Communities of Healthy and Diseased Malaysian Mahseer (Tor tambroides)
Authors: Lau Melinda Mei Lin , Kho Cindy Jia Yung , Lim Leonard Whye Kit , Sia Siew Chuiang , Chung Hung Hui , Lihan Samuel , Apun Kasing
Published: December 2021

Aims

The gut microbiota is referred to an ‘extra organ’ and is ciritical in assisting the host in terms of nutrition and immunity. Environmental stressors could alter gut microbial community and cause gut inflammation. This study aimed to investigate and compare the gut microbiota community between healthy and diseasedTor tambroides.

Methodology and results

In this study, such gut microbial alterations were explored using NGS-based 16S rDNA sequencing on the Malaysian mahseer (T. tambroides). Three adult healthy and three diseased adult Malaysian mahseers (showing signs of exophthalmia, coelomic distension and petechial haemorrhage) were obtained from LTT Aquaculture Sdn Bhd. Our results revealed significant differences in microbial diversity, composition and function between both populations ofT. tambroides.Alpha diversity analysis depicts lower diversity of gut microbiota composition in diseasedT. tambroidesas compared to the healthy group. In particular,Enterobacteriaceae,Aeromonas, Bacteroides, VibrioandPseudomonaswere found within gut microbiota of the diseased fishes. In addition, cellulose-degrading bacteria and protease-producing bacteria were identified from the gut ofT. tambroides.

Conclusion significance and impact of study

Thus, our findings emphasised on the association between the alteration in gut microbiota composition and infectious abdominal dropsy (IAD) inT. tambroides.This finding is important to provide basic information for further diagnosis, prevention and treatment of intestinal diseases in fish.
Multi-task Learning and Ensemble Approach to Predict Cognitive Scores for Patients with Alzheimer’s Disease
Authors: Ma Daren , Pabalan Christabelle , Rajagopal Abhejit , Akanksha Akanksha , Interian Yannet , Yang Yang , Raj Ashish
Published: December 2021

During its chronic degenerative course, Alzheimer’s Disease severely harms the patients’ cognitive abilities. Assessment of current and future cognition is an integral component of a diagnosis of dementia, and therefore an important clinical and scientific goal. Unfortunately, subjective, time-consuming and operator-sensitive clinical surveys or neuropyschiatric batteries remain the only viable methods of assessing cognition. Given that MRI is the most prevalent, cost-effective, and clinically important imaging modality, it may be considered a suitable predictor of cognition. Yet, it has hitherto proved very challenging to predict one from the other. We propose that an image-based Deep Learning model can be custom-built to achieve this goal. We designed a novel multi-task UNet model to predict the subjects’ current and future cognition (via ADAS-Cog scores), taking as input baseline T1-weighted MRI and demographic risk factors. The key innovation in the model is that it seeks to solve two adjacent but relevant tasks: image segmentation into tissue types; and prediction of cognition. The first task gives a high-accuracy brain segmentation, comparable to other cutting edge methods. The features trained from the segmentation task are used in the cognition task. This combination is far superior to stand-alone single-shot cognition models. We achieved excellent accuracy in both baseline and time-series forecast of ADAS-Cog scores. Through further feature map analysis made on the receptive fields, we managed to impart much-needed model interpretability, critical for real-world clinical practice. This study constitutes the best-reported performance of any comparable approach, and opens the door towards machine-based tracking of AD progression.
Leaders are made: Learning acquisition of consistent leader-follower relationships depends on implicit haptic interactions
Authors: Takai Asuka , Fu Qiushi , Doibata Yuzuru , Lisi Giuseppe , Tsuchiya Toshiki , Mojtahedi Keivan , Yoshioka Toshinori , Kawato Mitsuo , Morimoto Jun , Santello Marco
Published: December 2021

Are leaders made or born? Leader-follower roles have been well characterized in social science, but they remain somewhat obscure in sensory-motor coordination. Furthermore, it is unknown how and why leader-follower relationships are acquired, including innate versus acquired controversies. We developed a novel asymmetrical coordination task in which two participants (dyad) need to collaborate in transporting a simulated beam while maintaining its horizontal attitude. This experimental paradigm was implemented by twin robotic manipulanda, simulated beam dynamics, haptic interactions, and a projection screen. Clear leader-follower relationships were learned despite participants not being informed that they were interacting with each other, but only when strong haptic feedback was introduced. For the first time, we demonstrate the emergence of consistent leader-follower relationships in sensory-motor coordination, and further show that haptic interaction is essential for dyadic co-adaptation. These results provide insights into neural mechanisms responsible for the formation of leader-follower relationships in our society.
HDfleX: Software for flexible high structural resolution of hydrogen/deuterium-exchange mass spectrometry data
Authors: Seetaloo Neeleema , Kish Monika , Phillips Jonathan J.
Published: December 2021

Hydrogen/deuterium-exchange mass spectrometry (HDX-MS) experiments on protein structures can be performed at three levels: (1) by enzymatically digesting labelled proteins and analyzing the peptides (bottom-up), (2) by further fragmenting peptides following digestion (middle-down), and (3) by fragmenting the intact labelled protein (top-down), using soft gas-phase fragmentation methods, such as electron transfer dissociation (ETD). However, to the best of our knowledge, the software packages currently available for the analysis of HDX-MS data do not enable the peptide- and ETD-levels to be combined – they can only be analyzed separately. Thus, we developed HDfleX – a standalone application for the analysis of flexible high structural resolution of HDX-MS data, which allows data at any level of structural resolution (intact protein, peptide, fragment) to be merged. HDfleX features rapid experimental data fitting, robust statistical significance analyses and optional methods for theoretical intrinsic calculations and a novel empirical correction for comparison between solution conditions.
Life history adaptations to fluctuating environments: Combined effects of demographic buffering and lability of demographic parameters
Authors: Coeur Christie Le , Yoccoz Nigel G. , Salguero-Gómez Roberto , Vindenes Yngvild
Published: December 2021

Demographic buffering and lability have been identified as adaptive strategies to optimise fitness in a fluctuating environment. These are not mutually exclusive, however we lack efficient methods to measure their relative importance for a given life history. Here, we decompose the stochastic growth rate (fitness) into components arising from nonlinear responses and variance-covariance of demographic parameters to an environmental driver, which allows studying joint effects of buffering and lability. We apply this decomposition for 154 animal matrix population models under different scenarios, to explore how these main fitness components vary across life histories. Faster-living species appear more responsive to environmental fluctuations, either positively or negatively. They have the highest potential for strong adaptive demographic lability, while demographic buffering is a main strategy in slow-living species. Our decomposition provides a comprehensive framework to study how organisms adapt to variability through buffering and lability, and to predict species responses to climate change.
Quantification of microbial robustness
Authors: Trivellin Cecilia , Olsson Lisbeth , Rugbjerg Peter
Published: December 2021

Stable cell performance in a fluctuating environment is essential for sustainable bioproduction and synthetic cell functionality; however, microbial robustness is rarely quantified. Here, we describe a high-throughput strategy for quantifying robustness of multiple cellular functions and strains in a perturbation space. We evaluated quantifications theory on experimental data and concluded that the mean-normalized Fano factor allowed accurate, reliable, and standardized quantification. Our methodology applied to perturbations related to lignocellulosic bioethanol production showed that Saccharomyces cerevisiae Ethanol Red exhibited both higher and more robust growth rates than CEN.PK and PE-2, while a more robust product yield traded off for lower mean levels. The methodology validated that robustness is function-specific and characterized by positive and negative function-specific trade-offs. Systematic quantification of robustness to end-use perturbations will be important to analyze and construct robust strains with more predictable functions.

Graphical Abstract
Toxoplasma ERK7 defends the apical complex from premature degradation
Authors: O’Shaughnessy William J. , Hu Xiaoyu , Henriquez Sarah Ana , Reese Michael L.
Published: December 2021

Accurate cellular replication balances the biogenesis and turnover of complex structures. In the apicomplexan parasiteToxoplasma gondii,daughter cells form within an intact mother cell, creating additional challenges to ensuring fidelity of division. The apical complex is critical to parasite infectivity and consists of apical secretory organelles and specialized cytoskeletal structures. We previously identified the kinase ERK7 as required for maturation of the apical complex inToxoplasma. Here we define theToxoplasmaERK7 interactome, including a putative E3 ligase, CSAR1. Genetic disruption of CSAR1 fully suppresses loss of the apical complex upon ERK7 knockdown. Furthermore, we show that CSAR1 is normally responsible for turnover of maternal cytoskeleton during cytokinesis, and that its aberrant function is driven by mislocalization from the parasite residual body to the apical complex. These data identify a protein homeostasis pathway critical forToxoplasmareplication and fitness and suggest an unappreciated role for the parasite residual body in compartmentalizing processes that threaten the fidelity of parasite development.
A genetic disorder reveals a hematopoietic stem cell regulatory network co-opted in leukemia
Authors: Voit Richard A. , Tao Liming , Yu Fulong , Cato Liam D. , Cohen Blake , Liao Xiaotian , Fiorini Claudia , Nandakumar Satish K. , Wahlster Lara , Teichert Kristian , Regev Aviv , Sankaran Vijay G.
Published: December 2021

The molecular regulation of human hematopoietic stem cell (HSC) maintenance is therapeutically important, but limitations in experimental systems and interspecies variation have constrained our knowledge of this process. Here, we have studied a rare genetic disorder due toMECOMhaploinsufficiency, characterized by an early-onset absence of HSCsin vivo. By generating a faithful model of this disorder in primary human HSCs and coupling functional studies with integrative single-cell genomic analyses, we uncover a key transcriptional network involving hundreds of genes that is required for HSC maintenance. Through our analyses, we nominate cooperating transcriptional regulators and identify how MECOM prevents the CTCF-dependent genome reorganization that occurs as HSCs differentiate. Strikingly, we show that this transcriptional network is co-opted in high-risk leukemias, thereby enabling these cancers to acquire stem cell properties. Collectively, we illuminate a regulatory network necessary for HSC self-renewal through the study of a rare experiment of nature.
Targeting targeted memory reactivation: characteristics of cued reactivation in sleep
Authors: Abdellahi Mahmoud E. A. , Koopman Anne C. M. , Treder Matthias S. , Lewis Penelope A.
Published: December 2021

Targeted memory reactivation (TMR) is a technique in which sensory cues associated with memories during wake are used to trigger memory reactivation during subsequent sleep. The characteristics of such cued reactivation, and the optimal placement of TMR cues, remain to be determined. We built an EEG classification pipeline that discriminated reactivation of right- and left-handed movements and found that cues which fall on the up-going transition of the slow oscillation (SO) are more likely to elicit a classifiable reactivation. We also used a novel machine learning pipeline to predict the likelihood of eliciting a classifiable reactivation after each TMR cue using the presence of spindles and features of SOs. Finally, we found that reactivations occurred either immediately after the cue or one second later. These findings greatly extend our understanding of memory reactivation and pave the way for development of wearable technologies to efficiently enhance memory through cueing in sleep.
Inference for epidemic models with time varying infection rates: tracking the dynamics of oak processionary moth in the UK
Authors: Wadkin L E , Branson J , Hoppit A , Parker N G , Golightly A , Baggaley A W
Published: December 2021

Invasive pests pose a great threat to forest, woodland and urban tree ecosystems. The oak processionary moth (OPM) is a destructive pest of oak trees, first reported in the UK in 2006. Despite great efforts to contain the outbreak within the original infested area of South-East England, OPM continues to spread.

Here we analyse data of the numbers of OPM nests removed each year from two parks in London between 2013 and 2020. Using a state-of-the-art Bayesian inference scheme we estimate the parameters for a stochastic compartmental SIR (susceptible, infested, removed) model with a time varying infestation rate to describe the spread of OPM.

We find that the infestation rate and subsequent basic reproduction number have remained constant since 2013 (withR0between one and two). This shows further controls must be taken to reduceR0below one and stop the advance of OPM into other areas of England.

Synthesis.Our findings demonstrate the applicability of the SIR model to describing OPM spread and show that further controls are needed to reduce the infestation rate. The proposed statistical methodology is a powerful tool to explore the nature of a time varying infestation rate, applicable to other partially observed time series epidemic data.
Human cellular homeostasis buffers trans-acting translational effects of heterologous gene expression with very different codon usage bias
Authors: Jallet Arthur J , Demange Antonin , Leblay Fiona , Decourcelle Mathilde , El Koulali Khadija , Picard Marion AL , Bravo Ignacio G
Published: December 2021

The frequency of synonymous codons in protein coding genes is non-random and varies both between species and between genes within species. Whether this codon usage bias (CUBias) reflects underlying neutral mutational processes or is instead shaped by selection remains an open debate, especially regarding the role of selection for enhanced protein production. Variation in CUBias of a gene (be it natural synonymous mutations or biotechnological synonymous recoding) can have an enormous impact on its expression by diverse cis-acting mechanisms. But expression of genes with extreme CUBias can also lead to strong phenotypic effects by altering the overall intracellular translation homeostasis via competition for ribosomal machinery or tRNA depletion. In this study, we expressed at high levels in human cells six different synonymous versions of a gene and used matched transcriptomic and proteomic data to evaluate the impact of CUBias of the heterologous gene on the translation of cellular transcripts. Our experimental design focused specifically on differences during translation elongation. Response to expression of the different synonymous sequences was assessed by various approaches, ranging from analyses performed on a per-gene basis to more integrated approaches of the cell as a whole. We observe that the transcriptome displayed substantial changes as a result of heterologous gene expression by triggering an intense antiviral and inflammatory response, but that changes in the proteomes were very modest. Most importantly we notice that changes in translation efficiency of cellular transcripts were not associated with the direction of the CUBias of the heterologous sequences, thereby providing only limited support for trans-acting effects of synonymous changes. We interpret that, in human cells in culture, changes in CUBias can lead to important cis-acting effects in gene expression, but that cellular homeostasis can buffer the phenotypic impact of overexpression of heterologous genes with extreme CUBias.
Trade-offs among plant reproductive traits determine interactions with floral visitors
Authors: Lanuza Jose B. , Rader Romina , Stavert Jamie , Kendall Liam K. , Saunders Manu E. , Bartomeus Ignasi
Published: December 2021

Plant life-history strategies are constrained by cost-benefit trade-offs that determine plant form and function. However, despite recent advances in the understanding of trade-offs for vegetative and physiological traits, little is known about plant reproductive economics and how they constrain plant life-history strategies and shape interactions with floral visitors. Here, we investigate plant reproductive trade-offs and how these drive interactions with floral visitors using a dataset of 17 reproductive traits for 1,506 plant species from 28 plant-pollinator studies across 18 countries. We tested whether a plant’s reproductive strategy predicts its interactions with floral visitors and if the different reproductive traits predict the plant’s role within the pollination network. We found that over half of all plant reproductive trait variation was explained by two independent axes that encompassed plant form and function. Specifically, the first axis indicated the presence of a trade-off between flower number and flower size, while the second axis indicated a pollinator dependency trade-off. Plant reproductive trade-offs helped explain partly the presence or absence of interactions with floral visitors, but not differences in visitation rate. However, we did find important differences in the interaction level among floral visitor guilds on the different axes of trait variation. Finally, we found that plant size and floral rewards were the most important traits in the understanding of the plant species network role. Our results highlight the importance of plant reproductive trade-offs in determining plant life-history strategies and plant-pollinator interactions in a global context.
A mosaic bulk-solvent model improves density maps and the fit between model and data
Authors: Afonine Pavel V. , Adams Paul D. , Sobolev Oleg V. , Urzhumtsev Alexandre
Published: December 2021

Bulk solvent is a major component of bio-macromolecular crystals and therefore contributes significantly to diffraction intensities. Accurate modeling of the bulk-solvent region has been recognized as important for many crystallographic calculations, from computing ofR-factors and density maps to model building and refinement. Owing to its simplicity and computational and modeling power, the flat (mask-based) bulk-solvent model introduced by Jiang & Brunger (1994) is used by most modern crystallographic software packages to account for disordered solvent. In this manuscript we describe further developments of the mask-based model that improves the fit between the model and the data and aids in map interpretation. The new algorithm, here referred to asmosaic bulk-solvent model, considers solvent variation across the unit cell. The mosaic model is implemented in the computational crystallography toolbox and can be used inPhenixin most contexts where accounting for bulk-solvent is required. It has been optimized and validated using a sufficiently large subset of the Protein Data Bank entries that have crystallographic data available.

Synopsis

A mosaic bulk-solvent method models disordered solvent more accurately than current flat bulk solvent model. This improves the fit between the model and the data, improves map quality and allows for the solution of problems previously inaccessible.
High-throughput submicron-resolution microscopy of entire C. elegans populations under strong immobilization by cooling cultivation plates
Authors: Wang Yao L. , Jaklitsch Erik L. , Grooms Noa W. F. , Schulting Leilani G. , Chung Samuel H.
Published: December 2021

Despite its profound impact on biology, most high-resolution in vivo microscopy approaches remain low throughput because current immobilization techniques require significant manual effort. We greatly accelerate imaging of the nematode Caenorhabditis elegans by implementing a simple cooling approach to easily immobilize entire populations directly on their cultivation plates. We optimize and characterize cooling immobilization. Counterintuitively, relatively warmer temperatures immobilize animals significantly more effectively than colder temperatures utilized in prior studies. This enhanced immobilization enables clear submicron-resolution fluorescence imaging, which is challenging to achieve with most current immobilization techniques. We demonstrate 64× magnification 3D imaging and timelapse recording of neurons in adults and embryos without motion blur. Compared to standard azide immobilization, cooling immobilization reduces the animal preparation and recovery time by >98%, significantly increasing experimental speed. By obviating individual animal manipulation, our approach could also empower automated imaging of large C. elegans populations within standard experimental setups and workflows.
Contact sites between endoplasmic reticulum sheets and mitochondria regulate mitochondrial DNA replication and segregation
Authors: Ilamathi Hema Saranya , Benhammouda Sara , Lounas Amel , Al-Naemi Khalid , Desrochers-Goyette Justine , Lines Matthew A. , Richard François J. , Vogel Jackie , Germain Marc
Published: December 2021

Mitochondria are multi-faceted organelles crucial for cellular homeostasis that contain their own genome. Mitochondrial DNA (mtDNA) replication is a spatially regulated process essential for the maintenance of mitochondrial function, its defect causing mitochondrial diseases. mtDNA replication occurs at endoplasmic reticulum (ER)-mitochondria contact sites and is affected by mitochondrial dynamics: the absence of mitochondrial fusion is associated with mtDNA depletion whereas loss of mitochondrial fission causes the aggregation of mtDNA within abnormal structures termed mitobulbs. Here, we show that contact sites between mitochondria and ER sheets, the ER structure associated with protein synthesis, regulate mtDNA replication and distribution within mitochondrial networks. DRP1 loss or mutation leads to modified ER sheets and alters the interaction between ER sheets and mitochondria, disrupting RRBP1-SYNJ2BP interaction. Importantly, mtDNA distribution and replication were rescued by promoting ER sheets-mitochondria contact sites. Our work identifies the role of ER sheet-mitochondria contact sites in regulating mtDNA replication and distribution.
Biogenesis of a bacterial metabolosome for propanediol utilization
Authors: Yang Mengru , Wenner Nicolas , Dykes Gregory , Li Yan , Zhu Xiaojun , Sun Yaqi , Huang Fang , Hinton Jay C. D. , Liu Lu-Ning
Published: December 2021

Bacterial metabolosomes are a family of protein organelles in bacteria. Elucidating how thousands of proteins self-assemble to form functional metabolosomes is essential for understanding their significance in cellular metabolism and pathogenesis. Here we investigate thede novobiogenesis of propanediol-utilization (Pdu) metabolosomes and characterize the roles of the key constituents in generation and intracellular positioning of functional metabolosomes. Our results demonstrate that the Pdu metabolosome undertakes both “Shell first” and “Cargo first” assembly pathways, unlike the β-carboxysome structural analog which only involves the “Cargo first” strategy. Shell and cargo assemblies occur independently at the cell poles. The internal cargo core is formed through the ordered assembly of multiple enzyme complexes, and exhibits liquid-like properties within the metabolosome architecture. Our findings provide mechanistic insight into the molecular principles driving bacterial metabolosome assembly and expand our understanding of liquid-like organelle biogenesis.
Acute oral toxicity of zinc phosphide: an assessment for wild house mice in Australia
Authors: Hinds Lyn A. , Henry Steve , Van de Weyer Nikki , Robinson Freya , Ruscoe Wendy A. , Brown Peter R.
Published: December 2021

BACKGROUND

The efficacy of zinc phosphide (ZnP) for broadacre control of wild house mice in Australia is being reported by growers as increasingly variable. Have mice become less sensitive over time or are they taking a sub-lethal dose and developing aversion? In this laboratory study the sensitivity of groups of wild caught and an outbred laboratory strain of mice was assessed using oral gavage of a range of ZnP concentrations. The willingness of mice to consume ZnP-coated grains was then determined.

RESULTS

Each mouse group had very similar LD50 values (72 to 79 mg ZnP per kg body weight) which are significantly higher than previously reported. Time to death post-gavage ranged between 2.5 to 48 h. ZnP coated grains (50 g ZnP per kg grain) presented in the absence of alternative food were consumed and 94 percent of wild mice died. Mice provided with alternative food and ZnP coated wheat grains (either 25 or 50 g ZnP per kg grain) consumed toxic and non-toxic grains, and mortality was lower (33 to 55 percent). If a sublethal amount of ZnP coated grain was consumed, aversion occurred mostly in the presence of alternative food.

CONCLUSIONS

The sensitivity of wild house mice to ZnP in Australia is significantly lower than previously assumed. Under laboratory conditions ZnP coated grains coated with a new higher dose (50 g ZnP per kg grain) were readily consumed. Consumption of toxic grain occurred when alternative food was available but was decreased. It is important to assess the efficacy of the higher ZnP dose per grain under natural field conditions, especially when background food is low.
Salmonella Typhimurium induces NAIP/NLRC4- and NLRP3/ASC-independent, caspase-1/4-dependent inflammasome activation in human intestinal epithelial cells
Authors: Naseer Nawar , Bauer Renate , Zhang Jenna , Brodsky Igor E. , Rauch Isabella , Shin Sunny
Published: December 2021

Salmonella enterica serovar Typhimurium is a gram-negative pathogen that causes diseases ranging from gastroenteritis to systemic infection and sepsis. Salmonella uses type III secretion systems (T3SSs) to inject effectors into host cells. While these effectors are necessary for bacterial invasion and intracellular survival, intracellular delivery of T3SS products also enables detection of Salmonella by cytosolic immune sensors. Upon detecting translocated Salmonella ligands, these sensors form multimeric complexes called inflammasomes, which activate caspases that lead to proinflammatory cytokine release and pyroptosis. In particular, the Salmonella T3SS needle, inner rod, and flagellin proteins activate the NAIP/NLRC4 inflammasome in murine intestinal epithelial cells (IECs), which leads to restriction of bacterial replication and extrusion of infected IECs into the intestinal lumen, thereby preventing systemic dissemination of Salmonella. While these processes are studied quite well in mice, the role of the NAIP/NLRC4 inflammasome in human IECs remains unknown. Unexpectedly, we found the NAIP/NLRC4 inflammasome is dispensable for early inflammasome responses to Salmonella in both human intestinal epithelial cell lines and organoids. Additionally, the NLRP3 inflammasome and the adaptor protein ASC are not required for inflammasome activation in Caco-2 cells. Instead, we observed a partial requirement for caspase-1, and a necessity for caspase-4 and GSDMD pore-forming activity in mediating inflammasome responses to Salmonella in Caco-2 cells. These findings suggest that unlike murine IECs, human IECs do not rely on NAIP/NLRC4, and also do not use NLRP3/ASC. Instead, they primarily use caspases-1 and −4 to mediate early inflammasome responses to SPI-1-expressing Salmonella.
Cell cycle-dependent recruitment of FtsN to the divisome in Escherichia coli
Authors: Männik Jaana , Pichoff Sebastien , Lutkenhaus Joe , Männik Jaan
Published: December 2021

Cell division in Escherichia coli starts with the formation of an FtsZ protofilament network in the middle of the cell, the Z ring. However, only after a considerable lag period do the cells start to form a midcell constriction. The basis of this cell cycle checkpoint is yet unclear. The onset of constriction is dependent upon the arrival of so-called late divisome proteins, among which, FtsN is the last arriving essential one. The timing and dependency of FtsN arrival to the divisome, along with genetic evidence, suggests it triggers cell division. In this study, we used high throughput fluorescence microscopy to quantitatively determine the arrival of FtsN and the early divisome protein ZapA to midcell at a single-cell level during the cell cycle. Our data show that recruitment of FtsN coincides with the initiation of constriction within experimental uncertainties and that the relative fraction of ZapA/FtsZ reaches its highest value at this event. We also find that FtsN is recruited to midcell in two distinct temporal stages with septal peptidoglycan synthesis starting in the first stage and accelerating in the second stage, during which the amount of ZapA/FtsZ in the midcell decreases. In the presence of FtsA*, recruitment of FtsN becomes concurrent with the formation of the Z-ring, but constriction is still delayed indicating FtsN recruitment is not rate limiting, at least under these conditions. Finally, our data support the recently proposed idea that ZapA/FtsZ and FtsN are part of physically separate complexes in midcell throughout the whole septation process.

Importance

In E. coli, FtsN has been considered a trigger for septal wall synthesis and the onset of constriction. While FtsN is critical for cell division, its recruitment kinetics to midcell has not been characterized. Using quantitative high throughput microscopy, we find that FtsN is recruited to midcell in two temporal stages. The septal cell wall synthesis starts at the first stage and accelerates in the second stage. In the presence of an FtsA mutant defective in self-interaction, recruitment of FtsN to midcell is enhanced, but constriction is still delayed. Our results shed new light on an essential but not rate-limiting role of FtsN in E. coli cell division and also support the view that ZapA/FtsZ and FtsN are part of physically separate complexes in midcell throughout the division process.
Identification of functional residues using machine learning provides insights into the evolution of odorant receptor gene families in solitary and social insects
Authors: Mier Pablo , Fontaine Jean-Fred , Stoldt Marah , Libbrecht Romain , Martelli Carlotta , Foitzik Susanne , Andrade-Navarro Miguel A.
Published: December 2021

The gene family of insect odorant receptors (ORs) has greatly expanded in the course of evolution. ORs allow insects to detect volatile chemicals and therefore play an important role in social interactions, the detection of enemies and preys, and during foraging. The sequences of several thousand ORs are known, but their specific function or ligands have been identified only for very few of them. To advance the functional characterization of ORs, we compiled, curated and aligned the sequences of 3,902 ORs from 21 insect species. We identified the amino acid positions that best predict the response to ligands using machine learning on sets of functionally characterized proteins from the fly Drosophila melanogaster, the mosquito Anopheles gambiae and the ant Harpegnathos saltator. We studied the conservation of these predicted relevant residues across all OR subfamilies and show that the subfamilies that expanded strongly in social insects exhibit high levels of conservation in their binding sites. This indicates that ORs of social insect families are typically finely tuned and exhibit a sensitivity to very similar odorants. Our novel approach provides a powerful tool to use functional information from a limited number of genes to investigate the functional evolution of large gene families.
Topologically controlled circuits of human iPSC-derived neurons for electrophysiology recordings
Authors: Girardin Sophie , Clément Blandine , Ihle Stephan J. , Weaver Sean , Petr Jana B. , Mateus José C. , Duru Jens , Forró Csaba , Ruff Tobias , Fruh Isabelle , Müller Matthias , Vörös János
Published: December 2021

Bottom-up neuroscience, which consists of building and studying controlled networks of neuronsin vitro, is a promising method to investigate information processing at the neuronal level. However,in vitrostudies tend to use cells of animal origin rather than human neurons, leading to conclusions that might not be generalizable to humans and limiting the possibilities for relevant studies on neurological disorders. Here we present a method to build arrays of topologically controlled circuits of human induced pluripotent stem cell (iPSC)-derived neurons. The circuits consist of 4 to 50 neurons with mostly unidirectional connections, confined by microfabricated polydimethylsiloxane (PDMS) membranes. Such circuits were characterized using optical imaging and microelectrode arrays (MEAs). Electrophysiology recordings were performed on circuits of human iPSC-derived neurons for at least 4.5 months. We believe that the capacity to build small and controlled circuits of human iPSC-derived neurons holds great promise to better understand the fundamental principles of information processing and storing in the brain.
NovelPAX6variant in a family with ophthalmologic, pancreatic, and olfactory features
Authors: Buehne Kristen L. , Hart Sarah , Williams Bradley , Cohen Jennifer L.
Published: December 2021

Variants in thePAX6gene have been associated with ophthalmologic, neurologic, and pancreatic differences. We report on a proband, mother, and affected brother who presented with congenital cataracts and glaucoma at a young age. Nonocular findings are also reported among these family members. After a congenital cataracts next-generation sequencing (NGS) gene panel was found to be nondiagnostic in 2016, a more expanded panel in 2020 revealed a novel variant: c.178T > A; p.Tyr60Asn in exon 6 of thePAX6gene in the proband. The variant is also present in the affected mother and affected brother; it is absent in an unaffected brother. The clinical findings of these three relatives, in conjunction with their genetic testing and the associatedPAX6features reported in the literature, suggest that this novel familial variant may be an underlying etiology for these individuals’ ophthalmologic, pancreatic, and olfactory symptoms.
Role of Mn addition on the general corrosion and pitting corrosion behavior of 13Cr stainless steel
Authors: He Jun , Chen Lin , Su Yanjing
Published: December 2021

Purpose

The purpose of this study is to elucidate the effect of Mn addition on the corrosion behavior of stainless steel.

Design/methodology/approach

Chronoamperometry, quasi-steady-state polarization and electrochemical impedance spectroscopy were used to investigate the corrosion behavior of Mn added A13Cr-HS sample and original S13Cr samples. In addition, the corrosion product film was characterized by a field emission scanning electron microscope equipped with energy-dispersive spectroscopy and X-ray photoelectron spectroscopy.

Findings

The A13Cr-HS sample with 8 wt.% Mn addition maintained good general corrosion resistance in both acidic and alkaline solutions compared to the original S13Cr sample. Additionally, the A13Cr-HS sample had good pitting resistance in an alkaline solution containing Cl−, but a weaker resistance in an acidic solution.

Originality/value

The influence of Mn addition on the formation mechanism of the passive film was systematically analyzed.
Sizing by optimization of line-start synchronous motor
Authors: Knypiński Łukasz , Gillon Frédéric
Published: December 2021

Purpose

The purpose of this paper is to develop an algorithm and software for determining the size of a line-start permanent magnet synchronous motor (LSPMSMs) based on its optimization.

Design/methodology/approach

The software consists of an optimization procedure that cooperates with a FEM model to provide the desired behavior of the motor under consideration. The proposed improved version of the genetic algorithm has modifications enabling efficient optimization of LSPMSMs. The objective function consists of three important functional parameters describing the designed machine. The 2-D field-circuit mathematical model of the dynamics operation of the LSPMSMs consists of transient electromagnetic field equations, equations describing electric windings and mechanical motion equations. The model has been developed in the ANSYS Maxwell environment.

Findings

In this proposed approach, the set of design variables contains the variables describing the stator and rotor structure. The improved procedure of the optimization algorithm makes it possible to find an optimal motor structure with correct synchronization properties. The proposed modifications make the optimization procedure faster and more

Originality/value

This proposed approach can be successfully applied to solve the design problems of LSPMSMs.
Sociological traditions as a complementary lens to better understand digital transformation policies
Authors: C. Jackson Nicole , Corpakis Dimitri , Steiber Annika
Published: December 2021

Purpose

This paper aims to introduce how sociological traditions can provide a complementary, conceptual lens needed to better understand a country’s orientation in its digital transformation policies. While historically sociology has been used to study technological effects, introducing a sociological lens that considers broader macro digital policies can better complement a country’s national innovation system framework by highlighting where forms of acceleration and inertia in digital diffusion may or may not occur.

Design/methodology/approach

To formulate this lens, iterative literature reviews were conducted and four major sociological traditions (i.e. Durkheim, Functional-Utilitarian, Marxist and Micro-interactionist) were identified and integrated into one structure. The integrated structure was then applied to the French case of Minitel as a sample application. The French Minitel was selected because it is well-known and due to one of the author’s familiarity with the French culture. The description was based upon secondary data.

Findings

Through the use and application of this lens, the findings reveal that understanding a country’s specific orientation within a sociological tradition can help academics and practitioners determine what accelerates or provides inertia in the diffusion of new digital technologies within a country’s sociological frame. For the French Minitel, two dominant views seem to exist in France, the Durkheim and the Functional-Utilitarian view, which both affected the country’s path dependency in continued investments in Minitel.

Research limitations/implications

While policymakers are tasked with the development and implementation of digital transformation policies, a key consideration for both scholars and practitioners on digital policy and governance is to understand the broader macro ramifications of sociological frameworks on the evolving effects of digital transformation. While the authors provide a sample illustration, future research is needed to operationalize this lens and to apply it across various regions and countries in the development of new digital transformation policies.

Practical implications

As countries face considerable pressure to digitize their economies, policymakers require a better framework to advance the sociological aspects of digitization and its effects upon local institutions and actors in society. The paper provides a complementary lens that can better help them in this regard.

Originality/value

To date, policymakers and governments lack an integrated framework to understand the sociological effects of digital technologies and their diffusions along with their implications on societies such as on the framework of national innovation. The authors provide a sample integrated structure and sample application.
Work from home: understanding boundary management profiles using boundary-fit perspective
Authors: Kashive Neerja , Sharma Brijesh , Khanna Vandana Tandon
Published: December 2021

Purpose

The recent COVID-19 pandemic has (triggered) lots of interest in work from home (WFH) practices. Many organizations in India are changing their work practices and adopting new models of getting the work done. The purpose of the study to look at the boundary-fit perspective (Ammons (2013) and two factors, namely, individual preferences (boundary control, family identity, work identity and technology stress) and environmental factors (job control, supervisor support and organizational policies). These dimensions are used and considered to create various clusters for employees working from home.

Design/methodology/approach

K-mean clustering was used to do the cluster analysis. Statistical package for social sciences 23 was used to explore different clusters based on a pattern of characteristics unique to that cluster, but each cluster differed from other clusters. Further analysis of variance test was conducted to see how these clusters differ across three chosen outcomes, namely, work-family conflict, boundary management tactics used and positive family-to-work spillover effect. The post hoc test also provided insights on how each cluster differs from others on these outcomes.

Findings

The results indicated four distinct clusters named boundary-fit family guardians, work warriors, boundary-fit fusion lovers and dividers consistent (with previous) research. These clusters also differ across at least two major outcomes like boundary management tactics and positive spillover. The high control cluster profiles like Cluster 3 (boundary-fit fusion lovers) and Cluster 4 (dividers) showed low technostress and higher use of boundary management tactics. Cluster 3 (boundary-fit fusion lovers) and Cluster 1 (boundary-fit family guardians) having high environmental influencers also showed higher positive family-to-work spillover.

Research limitations/implications

Because this study is very specific to the Indian context, a broad generalization requires further exploration in other cultural contexts. The absence of this exploration is one of the limitations of this study. On the culture continuum, countries may vary from being individualistic on one extreme to being collectivistic on the other extreme. Interaction of these two cultural extremities with the individual and the environmental dimension, as espoused in this research, can be examined further in a different cultural setting.

Originality/value

This study has extended the work of Ammons (2013) and added external influencers as a dimension to the individual preferences given by (Kossek 2016), and created the cluster for employees in the Indian context. This study has demonstrated the importance of reduced technostress, and the use of boundary management tactics (temporal and behavioral) leads to positive family-to-work spillover. It has also emphasized the relevance of organization policies and supervisor support for better outcomes in WFH.