bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome sequences of Arthrobacter spp. that use a modified sulfoglycolytic Embden-Meyerhof-Parnas pathway
Authors: Kaur Arashdeep , van der Peet Phillip L. , Mui Janice W.-Y. , Herisse Marion , Pidot Sacha , Williams Spencer J.
Published: November 2021

Background

Sulfoglycolysis pathways enable the breakdown of the sulfosugar sulfoquinovose and environmental recycling of its carbon and sulfur content. Several pathways exist for the breakdown of sulfoquinovose that usually lead to production of C3-sulfonates (sulfolactate and 2,3-dihydroxypropanesulfonate) that are excreted and sustain secondary bacterial communities. The prototypical sulfoglycolytic pathway is a variant of the classical Embden-Meyerhof-Parnas pathway that has been described in gram-negative Escherichia coli and results in production of 2,3-dihydroxypropanesulfonate.

Results

We used enrichment cultures to discover new sulfoglycolytic bacteria from Australian soil samples. Two gram-positive Arthrobacter spp. were isolated that produced sulfolactate as the metabolic end-product. Genome sequences identified a modified sulfoglycolytic Embden-Meyerhof-Parnas (sulfo-EMP) gene cluster that retained the core sulfoglycolysis genes encoding metabolic enzymes, but featuring the replacement of the gene encoding sulfolactaldehyde (SLA) reductase with SLA dehydrogenase, and the absence of sulfoquinovosidase and sulfoquinovose mutarotase genes. The gene clusters were broadly conserved across a range of other sequenced Actinobacteria.

Conclusions

We report the first gram-positive soil bacteria that utilize sulfo-EMP pathways to metabolize SQ. Excretion of sulfolactate is consistent with an aerobic saprophytic lifestyle. This work broadens our knowledge of the sulfo-EMP pathway to include soil bacteria.
Prediction of molecular markers of bovine mastitis by meta-analysis of differentially expressed genes using combined p-value and robust rank aggregation
Authors: Umesh Anushri , Guttula Praveen Kumar , Gupta Mukesh Kumar
Published: November 2021

Bovine mastitis causes significant economic loss to the dairy industry by affecting milk quality and quantity. E.coli and S.aureus are the two common mastitis-causing bacteria among the consortia of mastitis pathogens, wherein E.coli is an opportunistic environmental pathogen, and S.aureus is a contagious pathogen. This study was designed to predict molecular markers of bovine mastitis by meta-analysis of differentially expressed genes (DEG) in E.coli or S.aureus infected mammary epithelial cells (MECs) using p-value combination and robust rank aggregation (RRA) methods. High throughput transcriptome of bovine (MECs, infected with E.coli or S.aureus, were analyzed, and correlation of z-scores were computed for the expression datasets to identify the lineage profile and functional ontology of DEGs. Key pathways enriched in infected MECs were deciphered by Gene Set Enrichment Analysis (GSEA), following which combined p-value and RRA were used to perform DEG meta-analysis to limit type I error in the analysis. The miRNA-Gene networks were then built to uncover potential molecular markers of mastitis. Lineage profiling of MECs showed that the gene expression levels were associated with mammary tissue lineage. The up-regulated genes were enriched in immune-related pathways whereas down-regulated genes influenced the cellular processes. GSEA analysis of DEGs deciphered the involvement of Toll-like receptor (TLR), and NF- Kappa B signalling pathway during infection. Comparison after meta-analysis yielded with genes ZC3H12A, RND1 and MAP3K8 having significant expression levels in both E.coli and S.aureus dataset and on evaluating miRNA-Gene network 7 pairs were common to both sets identifying them as potential molecular markers.
A Unified Genomic Mechanism of Cell-Fate Change
Authors: Tsuchiya Masa , Giuliani Alessandro , Zimatore Giovanna , Erenpreisa Jekaterina , Yoshikawa Kenichi
Published: November 2021

The purpose of our studies is to elucidate the nature of massive control of whole genome expression with a particular emphasis on cell-fate change. Whole genome expression is coordinated by the emergence of a critical point (CP: a peculiar set of bi-phasic genes) through the genome-engine. In response to stimuli, the genome expression self-organizes three critical states, each exhibiting distinct collective behaviors with its center of mass acting as a local attractor, coexisting with whole genome attractor (GA). Genome-engine mechanism accounts for local attractors interaction in phase space. The CP acts as the organizing center of cell-fate change, and its activation makes local perturbation spread over the genome affecting GA. The activation of CP is in turn elicited by ‘hot-spots’, genes with elevated temporal variance, normally in charge to keep genome expression at pace with microenvironment fluctuations. When hot-spots oscillation exceeds a given threshold, the CP synchronizes with the GA driving genome expression state transition. The expression synchronization wave invading the entire genome depends on the power law fusion-bursting dynamics of silencing pericentromere-associated heterochromatin domains and the consequent folding-unfolding status of transcribing euchromatin domains. The proposed mechanism is a unified step toward a time-evolutional transition theory of biological regulation.
A comprehensive LFQ benchmark dataset on modern day acquisition strategies in proteomics
Authors: Van Puyvelde Bart , Daled Simon , Willems Sander , Gabriels Ralf , de Peredo Anne Gonzalez , Chaoui Karima , Mouton-Barbosa Emmanuelle , Bouyssié David , Boonen Kurt , Hughes Christopher J. , Gethings Lee A. , Perez-Riverol Yasset , Bloomfield Nic , Tate Stephen , Schiltz Odile , Martens Lennart , Deforce Dieter , Dhaenens Maarten
Published: November 2021

In the last decade, a revolution in liquid chromatography-mass spectrometry (LC-MS) based proteomics was unfolded with the introduction of dozens of novel instruments that incorporate additional data dimensions through innovative acquisition methodologies, in turn inspiring specialized data analysis pipelines. Simultaneously, a growing number of proteomics datasets have been made publicly available through data repositories such as ProteomeXchange, Zenodo and Skyline Panorama. However, developing algorithms to mine this data and assessing the performance on different platforms is currently hampered by the lack of a single benchmark experimental design. Therefore, we acquired a hybrid proteome mixture on different instrument platforms and in all currently available families of data acquisition. Here, we present a comprehensive Data-Dependent and Data-Independent Acquisition (DDA/DIA) dataset acquired using several of the most commonly used current day instrumental platforms. The dataset consists of over 700 LC-MS runs, including adequate replicates allowing robust statistics and covering over nearly 10 different data formats, including scanning quadrupole and ion mobility enabled acquisitions. Datasets are available via ProteomeXchange (PXD028735).
Long-term culture system for deep-sea mussels Gigantidas childressi
Authors: Hiebenthal Claas , Gehlert Finn-Ole , Schmidt Mark , Reusch Thorsten B. H. , Melzner Frank
Published: November 2021

The simulation of deep-sea conditions in laboratories is technically challenging but necessary for experiments that aim at a deeper understanding of physiological mechanisms or host-symbiont interactions of deep-sea organisms. In a proof-of-concept study, we designed a recirculating system for long-term culture (>2 years) of deep-sea mussels Gigantidas childressi (previously Bathymodiolus childressi). Mussels were automatically (and safely) supplied with a maximum stable level of ~60 µM methane in seawater using a novel methane-air mixing system. Experimental animals also received daily doses of live microalgae. Condition indices of cultured G. childressi remained high over years, and low shell thickness growth could be detected, which is indicative of positive energy budgets. Using stable isotope data, we demonstrate that G. childressi in our culture system gained energy, both, from digestion of methane oxidizing endosymbionts and from digesting particulate food (microalgae). Limitations of the system, as well as opportunities for future experimental approaches involving deep-sea mussels are discussed.
Optimizing bulk segregant analysis of drug resistance using Plasmodium falciparum genetic crosses conducted in humanized mice
Authors: Brenneman Katelyn Vendrely , Li Xue , Kumar Sudhir , Delgado Elizabeth , Checkley Lisa A. , Shoue Douglas A. , Reyes Ann , Abatiyow Biley , Haile Meseret , Tripura Rupam , Peto Tom , Lek Dysoley , Button-Simons Katrina A. , Kappe Stefan H.I. , Dhorda Mehul , Nosten Francois , Nkhoma Standwell C. , Cheeseman Ian H , Vaughan Ashley M , Ferdig Michael T , Anderson Tim JC
Published: November 2021

Background: Classical genetic crosses in malaria parasites involve isolation, genotyping, and phenotyping of multiple progeny parasites, which is time consuming and laborious. Bulk segregant analysis (BSA) offers a powerful and efficient alternative to identify loci underlying complex traits in the human malaria parasite, Plasmodium falciparum.
Methods: We have used BSA, which combines genetic crosses using humanized mice with pooled sequencing of progeny populations to measure changes in allele frequency following selection with antimalarial drugs. We used dihydroartemisinin (DHA) drug selection in two genetic crosses (Mal31xKH004 and NF54xNHP1337). We specifically investigated how synchronization, cryopreservation, and the drug selection regimen of progeny pools impacted the success of BSA experiments.
Findings: We detected a strong and repeatable quantitative trait locus (QTL) at chr13 kelch13 locus in both crosses, but did not detect QTLs at ferredoxin (fd), the apicoplast ribosomal protein S10 (arps10), multidrug resistance protein 2 (mdr2). QTLs were detected using synchronized, but not unsynchronized pools, consistent with the stage-specific action of DHA. We also successfully applied BSA to cryopreserved progeny pools.
Interpretation: Our results provide proof-of-principal of the utility of BSA for rapid, robust genetic mapping of drug resistance loci. Use of cryopreserved progeny pools expands the utility of BSA because we can conduct experiments using archived progeny pools from previous genetic crosses. BSA provides a powerful approach that complements traditional QTL methods for investigating the genetic architecture of resistance to antimalarials, and to reveal new or accessory loci contributing to artemisinin resistance.
Emerging Accessibility Patterns in Long Telomeric Overhangs
Authors: Shiekh Sajad , Mustafa Golam , Kodikara Sineth G. , Hoque Mohammed Enamul , Yokie Eric , Portman John J. , Balci Hamza
Published: November 2021

We present single molecule experimental and computational modeling studies investigating the accessibility of human telomeric overhangs of physiologically relevant lengths. We studied 25 different overhangs that contain 4-28 repeats of GGGTTA (G-Tract) sequence and accommodate 1-7 tandem G-quadruplex (GQ) structures. Using FRET-PAINT method, we probed the distribution of accessible sites via a short imager strand, which is complementary to a G-Tract and transiently binds to available sites. We report accessibility patterns that periodically change with overhang length and interpret these patterns in terms of the underlying folding landscape and folding frustration. Overhangs that have [4n]G-Tracts, (12, 16, 20…), demonstrate the broadest accessibility patterns where the PNA probe accesses G-Tracts throughout the overhang. On the other hand, constructs with [4n+2]G-Tracts, (14, 18, 22…), have narrower patterns where the neighborhood of the junction between single and double stranded telomere is most accessible. We interpret these results as the folding frustration being higher in [4n]G-Tract constructs compared to [4n+2]G-Tract constructs. We also developed a computational model that tests the consistency of different folding stabilities and cooperativities between neighboring GQs with the observed accessibility patterns. Our experimental and computational studies suggest the neighborhood of the junction between single and double stranded telomere is least stable and most accessible, which is significant as this is a potential site where the connection between POT1/TPP1 (bound to single stranded telomere) and other shelterin proteins (localized on double stranded telomere) is established.

Significance Statement

The ends of eukaryotic linear chromosomes are capped by telomeres which terminate with a single-stranded overhang. Telomeric overhangs fold into compact structures, called G-quadruplex, that inhibit access to these critical genomic sites. We report single molecule measurements and computational modeling studies probing the accessibility of a set of human telomeric overhangs that covers a significant portion of the physiologically relevant length scale. We observe novel accessibility patterns which have a well-defined periodicity and show that certain regions are significantly more accessible than others. These accessibility patterns also suggest the underlying folding frustration of G-quadruplexes depends on telomere length. These patterns have significant implications for regulating the access of DNA processing enzymes and DNA binding proteins that can target telomeric overhangs.
Particle-associated and free-living microbial assemblages are distinct in a permanently redox-stratified freshwater lake
Authors: Cohen Ashley B. , Klepac-Ceraj Vanja , Butler Kristen , Weber Felix , Garber Arkadiy I. , Christensen Lisa N. , Cram Jacob A. , McCormick Michael L. , Taylor Gordon T.
Published: November 2021

Microbial assemblages associated with biogenic particles are phylogenetically distinct from free-living counterparts, yet biogeochemically coupled. Compositions may vary with organic carbon and inorganic substrate availability and with redox conditions, which determine reductant and oxidant availability. To explore microbial assemblage compositional responses to steep oxygen and redox gradients and seasonal variability in particle and substrate availability, we analyzed taxonomic compositions of particle-associated (PA) and free-living (FL) bacteria and archaea in permanently redox-stratified Fayetteville Green Lake. PA and FL assemblages (> 2.7 µm and 0.2 – 2.7 µm) were surveyed at the peak (July) and end (October) of concurrent cyanobacteria, purple and green sulfur bacteria blooms that result in substantial vertical fluxes of particulate organic carbon. Assemblage compositions varied significantly among redox conditions and size fractions (PA or FL). Temporal differences were only apparent among samples from the mixolimnion and oxycline, coinciding with seasonal hydrographic changes. PA assemblages of the mixolimnion and oxycline shifted from aerobic heterotrophs in July to fermenters, iron-reducers, and denitrifiers in October, likely reflecting seasonal variability in photoautotroph biomass and inorganic nitrogen. Within a light-scattering layer spanning the lower oxycline and upper monimolimnion, photoautotrophs were more abundant in July than in October, when Desulfocapsa, a sulfate-reducing and sulfur-disproportionating bacterium, and Chlorophyte chloroplasts were abundant in PA assemblages. In this layer, microbial activity and cell concentrations were also highest. Below, the most abundant resident taxa were sulfate-reducing bacteria and anaerobic respirers. Results suggest PA and FL assemblage niche partitioning interconnects multiple elemental cycles that involve particulate and dissolved phases.
Analysis of transcriptional changes in the immune system associated with pubertal development in a longitudinal cohort of children with asthma
Authors: Resztak Justyna , Choe Jane , Nirmalan Shreya , Wei Julong , Bruinsma Julian , Houpt Russell , Alazizi Adnan , Mair-Meijers Henriette E. , Wen Xiaoquan , Slatcher Richard B. , Zilioli Samuele , Pique-Regi Roger , Luca Francesca
Published: November 2021

Puberty is an important developmental period marked by hormonal, metabolic and immune changes. Puberty also marks a shift in sex differences in susceptibility to asthma. Yet, little is known about the gene expression changes in immune cells that occur during pubertal development. Here we assess pubertal development and leukocyte gene expression in a longitudinal cohort of 251 children with asthma. We identify substantial gene expression changes associated with age and pubertal development. Gene expression changes between pre- and post-menarcheal females suggest a shift from predominantly innate to adaptive immunity. We show that genetic effects on gene expression change dynamically during pubertal development. Gene expression changes during puberty are correlated with gene expression changes associated with asthma and may explain sex differences in prevalence. Our results show that molecular data used to study the genetics of early onset diseases should consider pubertal development as an important factor that modifies the transcriptome.
Variation in gene expression patterns across a conifer hybrid zone highlights the architecture of adaptive evolution under novel selective pressures
Authors: Menon Mitra , Swenson Jared , Moler Ehren , Whipple Amy V. , Waring Kristen M. , Eckert Andrew J.
Published: November 2021

Variation in gene expression among natural populations are key contributors to adaptive evolution. Understanding the architecture underlying adaptive trait evolution provides insights into the adaptive potential of populations exposed to novel selective pressures.

We investigated patterns and processes driving trait differentiation under novel climatic conditions by combining common garden experiments with transcriptome-wide datasets obtained from Pinus strobiformis - Pinus flexilis hybrid zone populations.

We found strong signals of genotype-environment interactions at the individual transcript and the co-expression module level, a marked influence of drought related variables on adaptive evolution and an environment dependent influence of P. flexilis ancestry on survival. Using co-expression network connectivity as a proxy for pleiotropy we highlight that adaptive transcripts were pleiotropic across both gardens and modules with strong population differentiation exhibited lower preservation across gardens.

Our work highlights the utility of integrating transcriptomics with space-for-time substitution studies to evaluate the adaptive potential of long-lived species. We conclude by suggesting that the combination of pleiotropic trait architectures and substantial genetic variation may enable long-lived forest tree species to respond to rapid shift in climatic conditions.
Highly efficient Runx1 enhancer eR1-mediated genetic engineering for fetal, child and adult hematopoietic stem cells
Authors: Koh Cai Ping , Bahirvani Avinash Govind , Wang Chelsia Qiuxia , Yokomizo Tomomasa , Ng Cherry Ee Lin , Du Linsen , Tergaonkar Vinay , Voon Dominic Chih-Cheng , Hosoi Hiroki , Sonoki Takashi , Michelle Mok Meng Huang , Niibori-Nambu Akiko , Zhang Yi , Perkins Archibald S. , Hossain Zakir , Tenen Daniel G. , Ito Yoshiaki , Venkatesh Byrappa , Osato Motomi
Published: November 2021

A cis-regulatory genetic element which targets gene expression to stem cells, termed stem cell enhancer, serves as a molecular handle for stem cell-specific genetic engineering. Here we show the generation and characterization of a tamoxifen-inducible CreERT2 transgenic (Tg) mouse employing previously identified hematopoietic stem cell (HSC) enhancer for Runx1, eR1 (+24m). Kinetic analysis of labeled cells after tamoxifen injection and transplantation assays revealed that eR1-driven CreERT2 activity marks dormant adult HSCs which slowly but steadily contribute to unperturbed hematopoiesis. Fetal and child HSCs which are uniformly or intermediately active were also efficiently targeted. Notably, a gene ablation at distinct developmental stages, enabled by this system, resulted in different phenotypes. Similarly, an oncogenic Kras induction at distinct ages caused different spectrums of malignant diseases. These results demonstrate that the eR1-CreERT2 Tg mouse serves as a powerful resource for the analyses of both normal and malignant HSCs at all developmental stages.
Use of Raman and Raman optical activity to extract atomistic details of saccharides in aqueous solution
Authors: Palivec Vladimír , Johannessen Christian , Kaminský Jakub , Martinez-Seara Hector
Published: November 2021

Sugars are crucial components in biosystems and industrial applications. In aqueous environments, the natural state of short saccharides or charged glycosaminoglycans is floating and wiggling in solution. Therefore, tools to characterize their structure in a native aqueous environment are crucial but not always available. Here, we show that a combination of Raman/ROA and, on occasions, NMR experiments with Molecular Dynamics (MD) and Quantum Mechanics (QM) is a viable method to gain insights into structural features of sugars in solutions. Combining these methods provides information about accessible ring puckering conformers and their proportions. It also provides information about the conformation of the linkage between the sugar monomers, i.e., glycosidic bonds, allowing for identifying significantly accessible conformers and their relative abundance. For mixtures of sugar moieties, this method enables the deconvolution of the Raman/ROA spectra to find the actual amounts of its molecular constituents, serving as an effective analytical technique. For example, it allows calculating anomeric ratios for reducing sugars and analyzing more complex sugar mixtures to elucidate their real content. Altogether, we show that combining Raman/ROA spectroscopies with simulations is a versatile method applicable to saccharides. It allows for accessing many features with precision comparable to other methods routinely used for this task, making it a viable alternative. Furthermore, we prove that the proposed technique can scale up by studying the complicated Raffinose trisaccharide, and therefore, we expect its wide adoption to characterize sugar structural features in solution.
Heat-induced transposition increases drought tolerance in Arabidopsis
Authors: Thieme Michael , Brêchet Arthur , Keller Bettina , Bucher Etienne , Roulin Anne C.
Published: November 2021

Eukaryotic genomes contain a vast diversity of transposable elements (TEs). Formerly often described as selfish and parasitic DNA sequences, TEs are now recognized as a source of genetic diversity and powerful drivers of evolution. Yet, because their mobility is tightly controlled by the host, studies experimentally assessing how fast TEs may mediate the emergence of adaptive traits are scare. Here, we show that the heat-induced transposition of a low-copy TE increases phenotypic diversity and leads to the emergence of drought-tolerant individuals in Arabidopsis thaliana. We exposed high-copy TE lines (hcLines) with up to ∼8 fold increased copy numbers of the heat-responsive ONSEN TE (AtCOPIA78) to drought as a straightforward and ecologically highly relevant selection pressure. We provide evidence for increased drought tolerance in five out of the 23 tested hcLines and further pinpoint one of the causative mutations to an exonic insertion of ONSEN in the ribose-5-phosphate-isomerase 2 gene. The resulting loss-of-function mutation caused a decreased rate of photosynthesis and water consumption. This is one of the rare empirical examples substantiating the adaptive potential of mobilized stress-responsive TEs in eukaryotes. Our work sheds light on the relationship between TEs and their hosts and demonstrates the importance of TE-mediated loss-of-function mutations in stress adaptation, particularly in the face of global warming.
Brain monoaminergic activity during predator inspection in the Trinidadian guppy (Poecilia reticulata)
Authors: Dimitriadou S. , Winberg S. , Thörnqvist P.-O. , Croft DP. , Darden SK.
Published: November 2021

To understand the processes underpinning social decision-making, we need to determine how internal states respond to information gathered from the social environment. Brain monoamine neurotransmitters are key in the appraisal of the social environment and can reflect the internal state underlying behavioural responses to social stimuli. Here we determined the effects of conspecific partner cooperativeness during predator inspection on brain monoamine metabolic activity in Trinidadian guppies (Poecilia reticulata). We quantified the concentration of dopamine, serotonin and their metabolites across brain sections sampled immediately after ostensibly experiencing cooperation or defection from social partners whilst inspecting a predator model. Our results indicate dopaminergic and serotonergic activity differs with the cooperativeness experienced; these different neurotransmission profiles are likely to affect the expression and regulation of downstream behaviours that ultimately contribute to the patterning of cooperative interactions among individuals in the population.

List of abbreviations used
SRSF3 is a key regulator of epicardial formation
Authors: Lupu Irina-Elena , Bruche Susann , Chakrabarti Anob M. , McCracken Ian R. , Carsana Tamara , Redpath Andia N. , Smart Nicola
Published: November 2021

The epicardium is a fundamental regulator of cardiac development and regeneration, functioning to secrete essential growth factors and to produce epicardium-derived cells (EPDCs) that contribute most coronary mural cells and cardiac fibroblasts. The molecular mechanisms controlling epicardial formation have not been fully elucidated. In this study, we found that the RNA-binding protein SRSF3 is highly expressed in the embryonic proepicardium and epicardial layer. Deletion ofSrsf3from the murine proepicardium led to proliferative arrest, which prevented proper epicardial formation. Induction ofSrsf3deletion after the proepicardial stage resulted in impaired epicardial proliferation and EPDC formation by E13.5. Single-cell RNA-sequencing showed SRSF3-depleted epicardial cells were eliminated, however, the surviving non-recombined cells became hyperproliferative and, remarkably, compensated for the early deficit, via a mechanism that involvedSrsf3up-regulation This unexpected finding attests the importance of SRSF3 in controlling epicardial proliferation, and highlights the significant confounding effect of mosaic recombination on embryonic phenotyping. Mapping the SRSF3–RNA interaction network by endogenous irCLIP identified binding to major cell cycle regulators, such asCcnd1andMap4k4, with both splicing and non-splicing roles. This research defines SRSF3 as a key regulator of epicardial cell proliferation.
Physiological changes throughout the ear due to age and noise - a longitudinal study
Authors: Blockley Alix , Ogle Daisy , Woodrow Charlie , Montealegre-Z Fernando , Warren Ben
Published: November 2021

Biological and mechanical systems, whether by their overuse or their aging, will inevitably fail. Hearing provides a poignant example of this with noise-induced and age-related hearing loss. Hearing loss is not unique to humans, however, and is experienced by all animals in the face of wild and eclectic differences in ear morphology and operation. Here we exploited the high throughput and accessible tympanal ear of the desert locust, Schistocerca gregaria (mixed sex) to rigorously quantify changes in the auditory system due to noise exposure (3 kHz pure tone at 126 dB SPL) and age. We analysed tympanal dispalcements, morphology of the auditory Müller’s organ and measured activity of the auditory nerve, the transduction current and electrophysiological properties of individual auditory receptors. We found that noise mildly and transiently changes tympanal displacements, decreases both the width of the auditory nerve and the transduction current recorded from individual auditory neurons. Whereas age – but not noise - decreases the number of auditory neurons and increases their resting potential. Multiple other properties of Müller’s organ were unaffected by either age or noise including: the number of supporting cells in Müller’s organ or the nerve, membrane resistance and capacitance of the auditory neurons. The sound-evoked activity of the auditory nerve decreased as a function of age and this decrease was exacerbated by noise, with the largest difference during the middle of their life span. This ‘middle-aged deafness’ pattern of hearing loss mirrors that found for humans exposed to noise early in their life.

Key point summary

Age and noise lead to hearing loss.

Tympanal displacements have a transient and delayed reduction after noise.

The number of auditory neurons decreases with age. The width of the auditory nerve is reduced with noise exposure.

Locusts repeatedly exposed to noise lost their hearing compared to silent controls, but their hearing became similar to old silent control locusts due to age-related hearing loss dominating.

The electrophysiological properties of the auditory neurons and the transduction current remained unchanged for aged locusts but repeated noise exposure led to a cumulative decrease in the transduction current.
Mechanical activation drives tenogenic differentiation of human mesenchymal stem cells in aligned dense collagen hydrogels
Authors: Park Hyeree , Nazhat Showan N. , Rosenzweig Derek H.
Published: November 2021

Tendons are force transmitting mechanosensitive tissues predominantly comprised of highly aligned collagen type I fibres. In this study, the recently introduced gel aspiration-ejection method was used to rapidly fabricate aligned dense collagen (ADC) hydrogel scaffolds. ADCs provide a biomimetic environment compared to traditional collagen hydrogels that are mechanically unstable and comprised of randomly oriented fibrils. The ADC scaffolds were shown to be anisotropic with comparable stiffness to immature tendons. Furthermore, the application of static and cyclic uniaxial loading, short-term (48 h) and high-strain (20%), resulted in a 3-fold increase in both the ultimate tensile strength and modulus of ADCs. Similar mechanical activation of human mesenchymal stem cell (MSC) seeded ADCs in serum- and growth factor-free medium induced their tenogenic differentiation. Both static and cyclic loading profiles resulted in a greater than 12-fold increase in scleraxis gene expression and either suppressed or maintained osteogenic and chondrogenic expressions. Following the 48 h mechanoactivation period, the MSC-seeded scaffolds were matured by tethering in basal medium without further external mechanical stimulation for 19 days, altogether making up 21 days of culture. Extensive cell-induced matrix remodeling and deposition of collagens type I and III, tenascin-C and tenomodulin were observed, where initial cyclic loading induced significantly higher tenomodulin protein content. Moreover, the initial short-term mechanical stimulation elongated and polarized seeded MSCs and overall cell alignment was significantly increased in those under static loading. These findings indicate the regenerative potential of the ADC scaffolds for short-term mechanoactivated tenogenic differentiation, which were achieved even in the absence of serum and growth factors that may potentially increase clinical translatability.

Graphical abstract
Toxoplasma gondii phosphatidylserine flippase complex ATP2B-CDC50.4 critically participates in microneme exocytosis
Authors: Bisio Hugo , Krishnan Aarti , Marq Jean-Baptiste , Soldati-Favre Dominique
Published: November 2021

Regulated microneme secretion governs motility, host cell invasion and egress in the obligate intracellular apicomplexans. Intracellular calcium oscillations and phospholipid dynamics critically regulate micronemes exocytosis. Despite its importance for the lytic cycle of these parasites, molecular mechanistic details about exocytosis are still missing. Some members of the P4-ATPases act as flippases, changing the phospholipid distribution by translocation from the outer to the inner leaflet of the membrane. Here, the localization and function of the repertoire of P4-ATPases was investigated across the lytic cycle of Toxoplasma gondii. Of relevance, ATP2B and the non-catalytic subunit cell division control protein 50.4 (CDC50.4) form a stable heterocomplex at the parasite plasma membrane, essential for microneme exocytosis. This complex is responsible for flipping phosphatidylserine (PS), which presumably acts as a lipid mediator for the organelle fusion with the plasma membrane. DOC2.1, a previously described key egress and invasion factor, is shown here to be affected in its function in egress upon mutation on residues putatively involved in calcium binding. This study points toward the importance of PS in microneme exocytosis and unveils subtle differences in the signaling cascades leading to organelle secretion between intracellular and extracellular parasites to ensure egress and invasion, respectively.

Author Summary

Biological membranes display diverse functions, including membrane fusion, which are conferred by a defined composition and organization of proteins and lipids. Apicomplexan parasites possess specialized secretory organelles (micronemes), implicated in motility, invasion and egress from host cells. Microneme exocytosis is already known to depends on phosphatidic acid for its fusion with the plasma membrane. Here we identify a type P4-ATPase and its CDC50 chaperone (ATP2B-CDC50.4) that act as flippase and contribute to the enrichment of phosphatidylserine (PS) in the inner leaflet of the parasite plasma membrane. PS and the previously described C2-containing protein DOC2.1 differentially participate in microneme exocytosis in the context of environmental changes. Overall, our results shed light on the importance membrane homeostasis and lipid composition in controlling microneme secretion.
Directionality of PYD filament growth determined by the transition of NLRP3 nucleation seeds to ASC elongation
Authors: Hochheiser Inga V. , Behrmann Heide , Hagelueken Gregor , Rodríguez-Alcázar Juan F. , Kopp Anja , Latz Eicke , Behrmann Elmar , Geyer Matthias
Published: November 2021

Inflammasomes sense intrinsic and extrinsic danger signals to trigger inflammatory responses and pyroptotic cell death. Homotypic pyrin domain (PYD) interactions of inflammasome forming Nod-like receptors with the adaptor protein ASC mediate oligomerization into helical filamentous assemblies. These supramolecular organizing centers recruit and activate caspase-1, which results in IL-1β family cytokine maturation and pyroptotic cell death. The molecular details of the critical step in signal transduction of inflammasome signaling, however, remain ill-defined. Here, we describe the cryo-EM structure of the human NLRP3 PYD filament at 3.6 Å resolution. We identify a unique pattern of highly polar interface residues that form the homomeric interactions leading to characteristic filament ends that we designate as A- and B-end, respectively. Coupling a titration polymerization assay to cryo-EM, we demonstrate that the ASC adaptor protein elongation on NLRP3 PYD filament seeds is unidirectional, associating exclusively to the B-end of the NLRP3 filament. Notably, NLRP3 and ASC PYD filaments exhibit the same symmetry in rotation and axial rise per subunit, allowing for a continuous transition between NLRP3 as the nucleation seed and ASC as the elongator. Integrating the directionality of filament growth, we present a molecular model of the ASC speck consisting of active NLRP3–NEK7, ASC, and Caspase-1 proteins.
Exploration of burnout in early-career construction management professionals in the USA
Authors: Franz Bryan , Wang Tong , Issa Raja Raymond
Published: November 2021

Purpose

Construction managers face many work-related stressors induced by unrealistic schedule expectations, tight budgets, and long hours. Over time, these stressors can result in both mental and physical exhaustion, a condition referred to as burnout. Early-career managers are a key worker demographic, as they represent the near-term future of the construction industry, yet they have a high risk for burnout. The purpose of this study is to explore the prevalence of burnout in new construction managers, and to identify which individual or work-related factors are associated with feelings of burnout.

Design/methodology/approach

Using the Maslach Burnout Inventory General Survey (MBI-GS), data from 146 early-career professionals (less than 10 years of experience) with construction management degrees in the USA were collected and analyzed using correlational and best subset regression techniques.

Findings

The results show that the early-career demographic in the USA experiences both the Emotional Exhaustion and Cynicism dimensions of burnout at comparable levels to prior studies with more mid-to-late career respondents. However, the Professional Efficacy dimension was significantly higher in early-career professionals than any other sample. No individual factors, such as gender, marital status, or number of children, were predictive of any dimension of burnout. Instead, only work-related factors including co-worker friendliness, opportunities for personal development and promotion, and the ability to control the work pacing were strongly associated with one or more dimensions of burnout.

Originality/value

This study is the first to explore burnout in the key early-career demographic for construction managers in the United States construction industry. This work provides evidence that organizational policies and culture have a greater efficacy in alleviating burnout in this demographic, when compared to the work–life balance of the individual.
Contributions and challenges of voluntary organizations towards the integration of refugees into the job market
Authors: da Silva Pablo Marlon Medeiros , El-Aouar Walid Abbas , Firmino Thaís Teles , de Sousa Juliana Carvalho , da Silva Wesley Vieira
Published: November 2021

Purpose

This study aims to understand the contributions and challenges of voluntary organizations towards the integration of refugees into the job market.

Design/methodology/approach

Descriptive research with a qualitative approach based on interpretivism was used, applied to mediators of social entities in the city of São Paulo, Brazil.

Findings

The findings of this study support the importance of voluntary organizations in the employment of refugees, based on background that will contribute directly to the training of displaced persons in the Brazilian labor market. Meanwhile, difficulties such as post-employment refugee monitoring, legislative obstacles to the verification of skills, structural and human capital limitations of mediators, the national economic crisis and the lack of government support are identified as the main challenges for long-term assistance to refugees.

Practical implications

The results of the study can foster greater participation of public policymakers and society in supporting the third sector, aiming at a greater reach in the provision of services of mediators for the effective integration of refugees in Brazil.

Originality/value

This study contributes to the literature on the integration of refugees into the labor market by demonstrating the importance of voluntary organizations in this process. It also demonstrates how the main challenges of the third sector in the Brazilian context impact its support in facilitating and maintaining the employment of displaced persons.
Identifying and classifying the contributing factors to financial resilience
Authors: Zahedi Javad , Salehi Mahdi , Moradi Mahdi
Published: November 2021

Purpose

This paper aims to identify, classify and rank the contributing factors to financial resilience.

Design/methodology/approach

The present study is of a mixed-method and significant contributing factors have been identified after analyzing and reviewing the literature on resilience and financial resilience. These factors were classified and ranked using the analytic hierarchy process method. This paper operationalizes the concept of financial resilience.

Findings

The study results show that consistency in production and sales, access to a reliable supply chain, management ability to environmental adaptability, regional dimension and social support from the government’s side are among the determining factors in financial resilience at the market level. Some elements such as flexibility, risk identification, income, foreign exchange benefits, innovation in presenting goods and services, firm size and responsiveness of partners and beneficiaries inside and outside the organization are among the leading contributing factors at the organization level and management manner. Finally, the staff’s efficiency in using organization resources, shareholder staff and learning culture in the organization are among the main contributing factors to financial resilience under the staff’s influence.

Originality/value

The study results may give managers direction to evaluate companies’ resilience, especially in the emerging economy; besides, it improves the literature on the topic.
Heterogeneous effect of oil production on environmental degradation: panel evidence from OPEC member countries
Authors: Danmaraya Ismail Aliyu , Jakada Aminu Hassan , Mahmood Suraya , Ibrahim Bello Alhaji , Ali Ahmad Umar
Published: November 2021

Purpose

The purpose of this paper is to look at the asymmetric effect of oil production on environmental degradation in OPEC member countries from 1970–2019.

Design/methodology/approach

The authors build a nonlinear panel ARDL–PMG model using the Shinet al.(2014) nonlinear autoregressive distributed lag (ARDL) approach in panel form to assess both the short- and long-run impact of positive and negative oil production movements on CO2emissions.

Findings

The result demonstrates that the variables are cointegrated. According to the linear long run coefficients, oil production, FDI inflows and economic growth both have a positive and significant relationship with CO2emissions, implying that they deteriorate environmental quality in OPEC countries, while renewable energy has a negative relationship with CO2, implying that increasing renewable energy improves environmental quality. The asymmetric findings prove that positive and negative shocks of oil production exert a positive effect on carbon emissions in short run and long run.

Research limitations/implications

To begin with, the empirical assessments do not include all OPEC member nations; researchers are advised to resolve this constraint by looking at the economies of other OPEC members. Albeit the lack of data for other energy sources may serve as another constraint of this research, future research is expected to broaden the current framework via other energy sources such as nuclear, electricity, biomass, solar as well as wind.

Originality/value

The research adds to the body of knowledge as many of the prevailing studies in the literature failed to look at the asymmetric effect of oil production on the quality of environment. This is another gap in the literature that the current study is set out to fill. This study adds oil production as an explanatory variable and helps to extend the existing literature for OPEC countries, which could propose a solution to deal with ensuing environmental issues.
Is lean a theory? Viewpoints and outlook
Authors: Åhlström Pär , Danese Pamela , Hines Peter , Netland Torbjørn H. , Powell Daryl , Shah Rachna , Thürer Matthias , van Dun Desirée H.
Published: November 2021

Purpose

Lean remains popular in a wide range of private and public sectors and continues to attract a significant amount of research. However, most of this research is not grounded in theory. This paper presents and discusses different expert viewpoints on the role of theory in lean research and practice and provides guidelines for future research.

Design/methodology/approach

Seven experienced lean authors independently provide their views to the question “is Lean a theory?” before Rachna Shah summarizes the viewpoints and provides a holistic outlook for lean research.

Findings

Authors agree, disagree and sometimes agree to disagree. However, a close look reveals agreement on several key points. The paper concludes that Lean is not a theory but has plenty of theoretical underpinnings. Many lean-related theories provide promising opportunities for future research.

Originality/value

As researchers, we are asked to justify our research drawing on “theory,” but what does that mean for a practice-driven phenomenon such as lean? This paper provides answers and directions for future research.
Exploring the digital humanities research agenda: a text mining approach
Authors: Joo Soohyung , Hootman Jennifer , Katsurai Marie
Published: November 2021

Purpose

This study aims to explore knowledge structure and research trends in the domain of digital humanities (DH) in the recent decade. The study identified prevailing topics and then, analyzed trends of such topics over time in the DH field.

Design/methodology/approach

Research bibliographic data in the area of DH were collected from scholarly databases. Multiple text mining techniques were used to identify prevailing research topics and trends, such as keyword co-occurrences, bigram analysis, structural topic models and bi-term topic models.

Findings

Term-level analysis revealed that cultural heritage, geographic information, semantic web, linked data and digital media were among the most popular topics in the recent decade. Structural topic models identified that linked open data, text mining, semantic web and ontology, text digitization and social network analysis received increased attention in the DH field.

Originality/value

This study applied existent text mining techniques to understand the research domain in DH. The study collected a large set of bibliographic text, representing the area of DH from multiple academic databases and explored research trends based on structural topic models.
How do transaction costs, capabilities and networks influence the procurement strategies of small agri-food firms? Evidence from the wine industry
Authors: Varella Miranda Bruno , Ross Brent , Franken Jason , Gómez Miguel
Published: November 2021

Purpose

The purpose of this study is to disentangle the drivers of adoption of procurement strategies in situations where small agri-food firms deal with constrained organizational choices. More specifically, the authors investigate the role of transaction costs, capabilities and networks in the definition of feasible “make-or-buy” choices in emerging wine regions.

Design/methodology/approach

This article analyzes a unique dataset of small wineries from five US states: Illinois, Michigan, Missouri, New York and Vermont. The reported results derive from both a hurdle model (i.e. a probit model and a truncated regression model) and a tobit model.

Findings

The results suggest the importance of trust as a replacement for formal governance structures whenever small firms deal with highly constrained sets of organizational choices. On the other hand, the level of dependence on a limited mix of winegrape varieties and the perception that these varieties are fundamental in building legitimacy help to explain higher rates of vertical integration.

Originality/value

This study is important because it sheds light on organizational constraints that affect millions of farmers across the globe. The study of “make-or-buy” decisions in agri-food supply chains has mostly relied on the implicit assumption that all organizational choices are available to every firm. Nevertheless, limited capabilities and the participation in low-density networks may constrain the ability of a firm to adopt a governance mechanism. Stated organizational preferences and actual organizational choices may thus differ.