bluuebunny/crossref_metadata_2025 huggingface dataset:
Frailty indices based on self-report, blood-based biomarkers and examination-based data in the Canadian Longitudinal Study on Aging
Authors: Blodgett Joanna M , Pérez-Zepeda Mario U , Godin Judith , Kehler D Scott , Andrew Melissa K , Kirkland Susan , Rockwood Kenneth , Theou Olga
Published: March 2022

Background

Frailty can be operationalised using the deficit accumulation approach, which considers health deficits across multiple domains. We aimed to develop, validate and compare three different frailty indices (FI) constructed from self-reported health measures (FI-Self Report), blood-based biomarkers (FI-Blood) and examination-based assessments (FI-Examination).

Methods

Up to 30,027 participants aged 45–85 years from the baseline (2011–2015) comprehensive cohort of the Canadian Longitudinal Study on Aging were included in the analyses. Following standard criteria, three FIs were created: a 48-item FI-Self Report, a 23-item FI-Blood and a 47-item FI-Examination. In addition a 118-item FI-Combined was constructed. Mortality status was ascertained in July 2019.

Results

FI-Blood and FI-Examination demonstrated broader distributions than FI-Self Report. FI-Self Report and FI-Blood scores were higher in females, whereas FI-Examination scores were higher in males. All FI scores increased nonlinearly with age and were highest at lower education levels. In sex and age-adjusted models, a 0.01 increase in FI score was associated with a 1.08 [95% confidence interval (CI): 1.07,1.10], 1.05 (1.04,1.06), 1.07 (1.05,1.08) and a 1.13 (1.11,1.16) increased odds of mortality for FI-Self Report, FI-Blood, FI-Examination and FI-Combined, respectively. Inclusion of the three distinct FI types in a single model yielded the best prognostic accuracy and model fit, even compared to the FI-Combined, with all FIs remaining independently associated with mortality.

Conclusion

Characteristics of all FIs were largely consistent with previously established FIs. To adequately capture frailty levels and to improve our understanding of the heterogeneity of ageing, FIs should consider multiple types of deficits including self-reported, blood and examination-based measures.
International Registry of Coronavirus Exposure in Pregnancy (IRCEP): Cohort Description and Methodological Considerations
Authors: Hernández-Díaz Sonia , Smith Louisa H , Dollinger Camille , Rasmussen Sonja A , Schisterman Enrique F , Bellocco Rino , Wyszynski Diego F
Published: March 2022

Limited data are available about the potential health effects of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pregnant women and their developing offspring. We established the International Registry of Coronavirus Exposure in Pregnancy (IRCEP) to provide data on the risk of major adverse obstetric and neonatal outcomes among women with varying degrees of severity and timing of coronavirus disease 2019 (COVID-19) during pregnancy. We describe here the cohort and share the lessons learned. The IRCEP enrolls women tested for SARS-CoV-2 or with a clinical diagnosis of COVID-19 during pregnancy and obtains information using an online data collection system. By March 2021, 17,532 participants from 77 countries had enrolled; 54% enrolled during pregnancy and 46% afterward. Among women with symptomatic COVID-19 with a positive SARS-CoV-2 test (n = 4,934), symptoms were mild in 41%, moderate in 52%, and severe in 7%; 7.7% were hospitalized for COVID-19 and 1.7% were admitted to an intensive care unit. The biggest challenges were retention of participants enrolled during pregnancy and the potential bias introduced when participants enroll after pregnancy outcomes are known. Multiple biases need to be considered and addressed when estimating and interpreting the effects of COVID-19 in pregnancy in these types of cohorts.
Classification of Coadjoint Orbits for Symplectomorphism Groups of Surfaces
Authors: Kirillov Ilia
Published: March 2022

We classify generic coadjoint orbits for symplectomorphism groups of compact symplectic surfaces with or without boundary. We also classify simple Morse functions on such surfaces up to a symplectomorphism.
Palatability and apparent total tract macronutrient digestibility of retorted black soldier fly larvae-containing diets and their effects on the fecal characteristics of cats consuming them
Authors: Do Sungho , Koutsos Elizabeth A , McComb Alejandra , Phungviwatnikul Thunyaporn , de Godoy Maria R C , Swanson Kelly S
Published: March 2022

There is a growing interest in using black soldier fly larvae (BSFL) due to its supposed sustainability and nutritional qualities. Because little research has been conducted to evaluate the use of BSFL in cats, our objective was to determine the palatability and apparent total tract macronutrient digestibility (ATTD) of BSFL-containing canned diets and the fecal characteristics of healthy adult cats consuming them. First, three palatability tests were conducted to compare the following diets: 1) diet with poultry byproduct meal (PBPM) and chicken serving as the primary protein sources (control) vs. diet with BSFL meal replacing PBPM (BSFL meal); 2) control vs. diet with whole BSFL replacing some PBPM and poultry fat (BSFL whole); and 3) control vs. diet with BSFL oil replacing poultry fat (BSFL oil). All diets were formulated to meet Association of American Feed Control Officials nutrient profiles for adult cats and were produced using a still retort. A paired t-test was conducted to analyze data from each palatability test, with a higher (P < 0.05) consumption ratio being observed for BSFL meal (1.93:1), BSFL whole (2.03:1), and BSFL oil (1.57:1). Second, 32 adult cats (20 females and 12 males; BW: 4.19 ± 0.55 kg; age: 3.3 ± 0.38 yr) were used in a completely randomized design study composed of a 21-d baseline period and a 70-d experimental period. Cats consumed the control diet during the baseline and were then allotted to one of four experimental diets (n = 8 per group): 1) control, 2) BSFL meal, 3) whole BSFL, and 4) BSFL oil. Fecal samples were collected after baseline and experimental periods for ATTD and fecal characteristic analysis. Fecal output was higher (P < 0.05) and fecal dry matter percentage was lower (P < 0.05) in cats fed BSFL meal than those fed BSFL oil. Organic matter, crude protein (CP), and energy ATTD were lower (P < 0.05) in cats fed BSFL meal than those fed BSFL oil or control. CP and energy ATTD were lower (P < 0.05) in cats fed BSFL whole than those fed BSFL oil. A few serum metabolites were affected by diet (P < 0.05) but remained within reference ranges. Hematology was not affected by diet (P > 0.05). Overall, our results suggest that BSFL-containing diets are palatable and do not negatively affect fecal characteristics or serum chemistry but may have slightly lower nutrient digestibilities in adult cats.
Polyamines protect boar sperm from oxidative stress in vitro
Authors: Li Rongnan , Wu Xiaodong , Zhu Zhendong , Lv Yinghua , Zheng Yi , Lu Hongzhao , Zhou Kaifeng , Wu De , Zeng Wenxian , Dong Wuzi , Zhang Tao
Published: March 2022

Sperm are susceptible to excessive reactive oxygen species (ROS). Spermine and spermidine are secreted in large amounts by the prostate and potent natural free radical scavengers and protect cells against redox disorder. Thus, we used boar sperm as a model to study the polyamines uptake and elucidate whether polyamines protected sperm from ROS stress. Seven mature and fertile Duroc boars (aged 15 to 30 mo) were used in this study. In experiment 1, spermine and spermidine (3.6 ± 0.3 and 3.3 ± 0.2 mmol/L, respectively) were abundant in seminal plasma, and the content of polyamine decreased (P < 0.05) after preservation at 17 °C for 7 d or incubation at 37 °C for 6 h. In experiment 2, using labeling of spermine or spermidine by conjugation with fluorescein isothiocyanate and ultra-high-performance liquid chromatography, we found that the accumulation of spermine or spermidine in sperm was inhibited by quinidine and dl-tetrahydropalmatine (THP, organic cation transporters [OCT] inhibitors, P < 0.05), but not mildronate and l-carnitine (organic cation/carnitine transporter [OCTN] inhibitors, P > 0.05). In experiment 3, the addition of spermine or spermidine (0.5 mmol/L) in the extender resulted in higher motility, plasma membrane and acrosome integrity, and lower ROS level after preservation in vitro at 17 °C for 7 d (P < 0.05). In experiment 4, in the condition of oxidative stress (treatment with H2O2 at 37 °C for 2 h), the addition of spermine (1 mmol/L) or spermidine (0.5 mmol/L) in extender increased activities of glutathione peroxidase, glutathione reductase, and glutathione S-transferase; reduced glutathione and oxidized glutathione ratio (P < 0.05); and alleviate oxidative stress-induced lipid peroxidation, DNA damage, mitochondrial membrane potential (ΔΨm) decline, adenosine triphosphate depletion, and intracellular calcium concentration ([Ca2+]i) overload (P < 0.05), thereby improving boar sperm motility, the integrity of plasma membrane and acrosome (P < 0.05) in vitro. These data suggest that spermine and spermidine alleviate oxidative stress via the antioxidant capacity, thereby improving the efficacy of boar semen preservation.
Evaluation of Standardized Bait Trapping Approaches and Climatic Factors That Influence Wireworm Catch in the Canadian Prairies
Authors: Drahun Ivan , Hunt Katherine A , van Herk Willem G , Cassone Bryan J
Published: March 2022

Wireworms are significant pests of a variety of economically important crops grown in the Canadian Prairies. These soil-dwelling larvae of click beetles feed on and burrow into the accessible underground plant tissues, which can result in cosmetic injury, stunting, wilting, and plant death. Successful management of wireworms relies on accurate estimations of their abundance and activity in infested fields. Bait trapping is the most commonly used method for sampling wireworms and standardized approaches have been developed; however, little work has been done to optimize trapping efficacy in different geographical regions. In this study, we evaluated the effect of bait trapping duration, seed formulation, and the causal relationship with CO2 production and soil temperature on the wireworm catch in three fields located in Manitoba, Canada. As expected, wireworm catch increased with trapping duration and placing traps in ground for 8 d is adequate in most cases. Both barley and wheat were more effective baits than soybean; however, barley released more CO2 (i.e., an attractant for wireworms) and performed better at elevated soil temperatures. Overall, the results of this study will serve as valuable guidelines to improve current wireworm sampling methods, and can be integrated into strategies aimed at managing these important pests to crop production.
Cerambycid Pheromones 3,2-Hydroxyketones Affect Catches of Some Bark and Ambrosia Beetles (Coleoptera: Curculionidae) in Ethanol-Baited Multiple-Funnel Traps in Southeastern United States
Authors: Miller D R , Sweeney J D
Published: March 2022

In 2012–2013, we assessed the interactive effects of the cerambycid pheromones syn-2,3-hexanediol, 3-hydroxyhexan-2-one, and 3-hydroxyoctan-2-one on catches of bark and ambrosia beetles (Coleoptera: Curculionidae) in ethanol-baited multiple-funnel traps in north Georgia and South Carolina. We found that catches for nine of eleven species of ambrosia beetles in ethanol-baited traps were either unaffected or enhanced by the addition of 3,2-hydroxyketones. Similarly catches of five species of bark beetles were either unaffected or enhanced by the addition of 3,2-hydroxyketones. In particular, catches of Xylosandrus crassiusculus (Motschulsky), Cnestus mutilatus (Blandford), and Monarthrum fasciatum (Say) in ethanol-baited traps increased with the addition of 3-hydroxyhexan-2-one and/or 3-hydroxyoctan-2-one. Catches of the bark beetles Hylocurus rudis (LeConte) and Hypothenemus rotundicollis (Eichhoff) were enhanced by the addition of 3-hydroxyhexan-2-one and 3-hydroxyoctan-2-one, respectively. syn-2,3-Hexanediol had no effect on catches of bark and ambrosia beetles in ethanol-baited traps. Our data provide support for the use of ethanol + cerambycid pheromones for targeting non-native species of bark and ambrosia beetles as well as cerambycids in detection programs.
‘Going home when it was not home’: Jamais Vu in Nineteenth-Century British Fiction
Authors: Tett Sam
Published: March 2022

‘Jamais vu’ is a strange mnemonic disturbance that we continue to experience today, though few of us know what to call it. French for ‘never seen,’ jamais vu is the opposite of déjà vu (‘already seen’), and is defined as the temporary inability to recognize familiar things, people, and/or contexts. This essay comprises, to my knowledge, the first literary history of jamais vu. I begin by describing the complex features of this mnemonic disturbance, and uncovering its lost Victorian scientific archive. Though jamais vu went without a name until the 1920s, I also find it hiding in plain sight in nineteenth-century novels as early as Jane Austen’s Mansfield Park, as well as in the work of Charles Dickens, William Makepeace Thackeray, George Eliot, and Elizabeth Gaskell. From here, I follow jamais vu’s trajectory from realist accounts of everyday life into mid-century representations of the haunted house, where it becomes something more than a mnemonic disturbance. By attending to literary representations of jamais vu avant la lettre, I demonstrate its importance not just as a lost Victorian scientific concept, but also as a rich interdisciplinary category that is of great interest to scholars of the nineteenth century and beyond. Specifically, I show that jamais vu was integral to the development and popularity of the Victorian gothic, through which movement it exceeded its status as a mnemonic disturbance, re-emerging as a pervasive modern affect that we have inherited from the Victorians.
Handwriting Kinematics in Patients with Schizophrenia Treated with Long-Acting Injectable Atypical Antipsychotics: Results From the ALPINE Study
Authors: Caligiuri Michael P , Weiden Peter J , Legedza Anna , Yagoda Sergey , Claxton Amy
Published: March 2022

Handwriting kinematics (HWKs) were assessed in the randomized controlled ALPINE study of 2 long-acting injectable antipsychotics started during an acute exacerbation of schizophrenia. This exploratory analysis examined the relationship between baseline HWKs and response to acute antipsychotic treatment. Adults with acute schizophrenia were assigned to aripiprazole lauroxil or paliperidone palmitate (groups combined for this analysis). Treatment response was defined as ≥20% reduction from baseline in Positive and Negative Syndrome Scale (PANSS) total score at week 4. Two HWK measures, peak velocity (decreases with greater dysfunction) and percentage of nonballistic movements (%NBM; increases with greater dysfunction), were captured in 4 handwriting tasks (complex loops, maximum speed circles, overlay circles, and left-right loops). Peak velocity and %NBM at baseline were compared between responders and nonresponders. The analysis included 143 patients (mean baseline PANSS total score, 94.5). PANSS responders (n = 67 [46.9%]) had a lower mean peak velocity (i.e., slower pen movements) on all HWK tasks at baseline compared with nonresponders (n = 76): complex loops, 8.8 versus 12.1 cm/s; maximum speed circles, 18.0 versus 23.7 cm/s; overlay circles, 12.6 versus 17.2 cm/s; and left-right loops, 11.2 versus 14.6 cm/s. PANSS responders had a greater %NBM on 3 tasks compared with nonresponders: complex loops, 57.1% versus 47.4%; overlay circles, 30.6% versus 24.3%; and left-right loops, 58.7% versus 47.0%. In this exploratory analysis, PANSS responders to aripiprazole lauroxil or paliperidone palmitate treatment at week 4 had lower baseline HWK movement velocities and greater baseline %NBM versus nonresponders, suggesting that baseline HWKs might predict response to these antipsychotic drugs.
Workflow Optimization for Identification of Female Germline or Oogonial Stem Cells in Human Ovarian Cortex Using Single-Cell RNA Sequence Analysis
Authors: Alberico Hannah , Fleischmann Zoë , Bobbitt Tyler , Takai Yasushi , Ishihara Osamu , Seki Hiroyuki , Anderson Richard A , Telfer Evelyn E , Woods Dori C , Tilly Jonathan L
Published: March 2022

In 2004, the identification of female germline or oogonial stem cells (OSCs) that can support post–natal oogenesis in ovaries of adult mice sparked a major paradigm shift in reproductive biology. Although these findings have been independently verified, and further extended to include identification of OSCs in adult ovaries of many species ranging from pigs and cows to non–human primates and humans, a recent study rooted in single–cell RNA sequence analysis (scRNA-seq) of adult human ovarian cortical tissue claimed that OSCs do not exist, and that other groups working with OSCs following isolation by magnetic-assisted or fluorescence-activated cell sorting have mistaken perivascular cells (PVCs) for germ cells. Here we report that rare germ lineage cells with a gene expression profile matched to OSCs but distinct from that of other cells, including oocytes and PVCs, can be identified in adult human ovarian cortical tissue by scRNA-seq after optimization of analytical workflow parameters. Deeper cell-by-cell expression profiling also uncovered evidence of germ cells undergoing meiosis-I in adult human ovaries. Lastly, we show that, if not properly controlled for, PVCs can be inadvertently isolated during flow cytometry protocols designed to sort OSCs because of inherently high cellular autofluorescence. However, human PVCs and human germ cells segregate into distinct clusters following scRNA-seq due to non–overlapping gene expression profiles, which would preclude the mistaken identification and use of PVCs as OSCs during functional characterization studies.
Modernizing the NEURON Simulator for Sustainability, Portability, and Performance
Authors: Awile Omar , Kumbhar Pramod , Cornu Nicolas , Dura-Bernal Salvador , King James Gonzalo , Lupton Olli , Magkanaris Ioannis , McDougal Robert A. , Newton Adam J.H. , Pereira Fernando , Săvulescu Alexandru , Carnevale Nicholas T. , Lytton William W. , Hines Michael L. , Schürmann Felix
Published: March 2022

Abstract

The need for reproducible, credible, multiscale biological modeling has led to the development of standardized simulation platforms, such as the widely-used NEURON environment for computational neuroscience. Developing and maintaining NEURON over several decades has required attention to the competing needs of backwards compatibility, evolving computer architectures, the addition of new scales and physical processes, accessibility to new users, and efficiency and flexibility for specialists. In order to meet these challenges, we have now substantially modernized NEURON, providing continuous integration, an improved build system and release workflow, and better documentation. With the help of a new source-to-source compiler of the NMODL domain-specific language we have enhanced NEURON’s ability to run efficiently, via the CoreNEURON simulation engine, on a variety of hardware platforms, including GPUs. Through the implementation of an optimized in-memory transfer mechanism this performance optimized backend is made easily accessible to users, providing training and model-development paths from laptop to workstation to supercomputer and cloud platform. Similarly, we have been able to accelerate NEURON’s reaction-diffusion simulation performance through the use of just-in-time compilation. We show that these efforts have led to a growing developer base, a simpler and more robust software distribution, a wider range of supported computer architectures, a better integration of NEURON with other scientific workflows, and substantially improved performance for the simulation of biophysical and biochemical models.
Elevated p21 (CDKN1a) mediates β-thalassemia erythroid apoptosis but its loss does not improve β-thalassemic erythropoiesis
Authors: Menon Vijay , Lin Miao , Liang Raymond , Arif Tasleem , Menon Anagha , Breda Laura , Rivella Stefano , Ghaffari Saghi
Published: March 2022

β-thalassemias are common hemoglobinopathies due to mutations in the β-globin gene that lead to hemolytic anemias. Premature death of β-thalassemic erythroid precursors results in ineffective erythroid maturation, increased production of erythropoietin (Epo), expansion of erythroid progenitor compartment, extramedullary erythropoiesis and splenomegaly. However, the molecular mechanism of erythroid apoptosis in β-thalassemia is not well understood. Using a mouse model of β-thalassemia (Hbbth3/+), we show that dysregulated expression of Foxo3 transcription factor and its upstream pro-apoptotic regulator TP53 is implicated in β-thalassemia erythroid apoptosis. In Foxo3-/-/Hbbth3/+ mice, erythroid apoptosis is significantly reduced while erythroid cell maturation, red blood cell and hemoglobin production are substantially improved. However, persistence of elevated reticulocytes and splenomegaly suggests that ineffective erythropoiesis is not resolved in Foxo3-/-/Hbbth3/+. We next focused on cell cycle inhibitor Cdkn1a (p21) and show that p21 that is a target of both Foxo3 and TP53 is markedly upregulated in both mouse and patients-derived β-thalassemic erythroid precursors. To address the contribution of p21 to β-thalassemia pathophysiology, we generated p21-/-/Hbbth3/+ mice. Double mutant p21/Hbbth3/+ mice exhibited embryonic lethality with only a fraction of mice surviving to weaning. Notably, studies in adult mice showed apoptosis and circulating Epo were greatly reduced in erythroid compartments of surviving p21-/-/Hbbth3/+ relative to Hbbth3/+ mice, while ineffective erythroid cell maturation, extramedullary erythropoiesis and splenomegaly were not modified. These combined results indicate that while lack of Foxo3 reduces apoptosis and improves anemia, diminished p21-mediated apoptosis is insufficient to improve red blood cell production in Hbbth3/+ mice. They also suggest that a molecular network constituted by p21, FOXO3 and TP53, control erythroid cell survival and differentiation in β-thalassemia. Overall, these studies provide a new framework for investigating ineffective erythropoiesis in β-thalassemia.

Key Points

Elevated p21 mediates β-thalassemia erythroid cell apoptosis

Loss of Foxo3 or p21 reduces β-thalassemia erythroid cell apoptosis but does not improve β-thalassemia ineffective erythropoiesis

A network of Foxo3, p21 and TP53 controls β-thalassemia erythroid apoptosis

Apoptosis may be uncoupled from ineffective erythropoiesis in β-thalassemia
Development and evaluation of a loop-mediated isothermal amplification (LAMP) method for detection of the potato wart pathogen Synchytrium endobioticum
Authors: Jiang Junye , Feindel Will , Feindel David , Bajema Stacey , Feng Jie
Published: March 2022

Potato (Solanum tuberosum) wart, caused by the biotrophic fungal pathogen Synchytrium endobioticum, is a serious disease of cultivated potatoes. A rapid and accurate method for wart diagnosis is needed. In this study, we described the development and evaluation of a loop-mediated isothermal amplification (LAMP) method for the detection of S. endobioticum. Four sets of LAMP primers were designed. Their sensitivity was tested on a gBlock and the specificity of the most sensitive primer set (LAMP1) was verified by in silico analysis and on DNA of non-target species. The LAMP1 primer set showed a detection limit at 7-8 gBlock DNA molecules per reaction. On sensitivity, the LAMP was comparable to qPCR (SYBR green- and probe-based) and about 10 times more sensitive than conventional PCR. Considering the convenience of operation, the LAMP protocol is accurate and robust and should be recommended for the routine lab testing for potato wart.
Temporal and spatial dynamics mapping reveals follicle development regulated by different stromal cell populations
Authors: Sheng Xiaoqiang , Zhou Jidong , Kang Nannan , Liu Wenwen , Yu Lina , Zhang Zhe , Zhang Yang , Yue Qiuling , Yang Qiwen , Zhang Xinke , Li Chaojun , Yan Guijun , Sun Haixiang
Published: March 2022

Follicle development is a complex dynamic process. The follicles are encapsulated in the stroma, and once the follicle develops, the follicle moves from the cortex to the medulla and finally to the cortex to ovulate in the process of continuous growth. Many of these processes cannot be explained with the follicle alone. Through single-cell and spatial transcriptome sequencing at key time points of follicular development in mice after birth, we found that ovarian stromal cells are not only one of the main cell groups that make up the ovary but that their cell population and spatial location are also closely related to follicular development. Through analysis of cell communication, it was found that ovarian stromal cells were the main transmitters of intercellular communication, and many of the signals they sent were received by granulosa cells and oocytes to participate in follicle development. Ovarian stromal cells are not a homogeneous cell population. We combined single cell types with their spatial location information to divide ovarian stromal cells into four types, namely, structural stromal cells, perifollicular stromal cells, stromal progenitor cells, and steroidogenic stromal cells, each of which plays a different function in follicle development. Indepth studies of the different spatial locations and different types of stromal cells will expand our understanding of follicle development dynamics, leading to new targets and novel approaches for the treatment of ovarian-related diseases.
Near Infrared-II Fluorescent protein for In-vivo Imaging
Authors: Chang Zong , Liu ChenChen , Zhao Shubi , Chen Jiaqi , Zhang Xiaoping , Tian Hanyu , Sun Qinchao
Published: March 2022

In vivo fluorescent imaging in the second near-infrared window (NIR-II) provides an excellent approach for understanding the biological processes in substantially scattered tissue environments with reasonable temporal-spatial resolution. In spite of an enormous amount of organic and inorganic NIR-II fluorophores developed, there is no NIR-II fluorescent protein reported. Here, we present the first NIR-II fluorescent protein, IRFP1032 which exhibits strong exciton absorption and emission in the NIR-II region, with exciton extinction coefficient about 4.1 ×106 M-1cm-1 at the excitation maximum 1008 nm, emission maximum of 1032 nm, and emission quantum yield about 0.84%. The IRFP1032 is found to be the brightest NIR-II fluorophore ever reported (brightness of 3.4 × 104 M-1cm-1 in PBS) which is thousands-fold brighter than IR26 in DCM. Taking the advantage of the excellent photo-properties of the NIR-II fluorescent proteins, a collection of high-quality in vivo imaging research was realized, for instance, real time observation of blood flow dynamics, dual-channel imaging of the lymphatic/blood vessel network and the trajectories of single bacterial cell travelling in blood vessels. Moreover, a mammalian expression vector was constructed for the IRFP1032, and the corresponding NIR-II fluorescence was able to be recorded unambiguously. The promising NIR-II in vivo imaging properties of IRPF1032 demonstrated here would open a new scene in fluorescent protein-based imaging.
Effects of somatic mutations on cellular differentiation in iPSC models of neurodevelopment
Authors: Puigdevall Pau , Jerber Julie , Danecek Petr , Castellano Sergi , Kilpinen Helena
Published: March 2022

The use of induced pluripotent stem cells (iPSC) as models for development and human disease has enabled the study of otherwise inaccessible tissues. A remaining challenge in developing reliable models is our limited understanding of the factors driving irregular in vitro differentiation of iPSCs, particularly the impact of acquired somatic mutations. We leveraged data from a pooled dopaminergic neuron differentiation experiment of 238 iPSC lines profiled with single-cell and whole-exome sequencing to study how somatic mutations affect differentiation outcomes. Differentiation was tracked at three time points corresponding to neural progenitors, early neurons and mature neurons. We found that deleterious somatic mutations in key developmental genes, notably the BCOR gene, are strongly associated with failure in dopaminergic neuron differentiation, with lines carrying such mutations also showing larger proliferation rate in culture. We further identified broad differences in cell type composition between failed and successfully differentiating lines, as well as significant changes in gene expression contributing to the inhibition of neurogenesis, a functional process also targeted by deleterious mutations in failed lines. Our work highlights the need to routinely measure the burden of deleterious mutations in iPSC lines and calls for caution in interpreting differentiation-related phenotypes in disease-modelling experiments.
Ultrastructural analysis of wildtype and RIM1α knock-out active zones in a large cortical synapse
Authors: Lichter Katharina , Paul Mila Marie , Pauli Martin , Schoch Susanne , Kollmannsberger Philip , Stigloher Christian , Heckmann Manfred , Sirén Anna-Leena
Published: March 2022

Rab3A-interacting molecule (RIM) is crucial for fast Ca2+-triggered synaptic vesicle (SV) release in presynaptic active zones (AZ). While loss of RIM1α impairs long-term plasticity at hippocampal giant mossy fiber boutons (MFB), it remains unclear how AZ ultrastructure is altered. We investigated MFB AZ architecture in 3D using electron tomography of rapid cryo-immobilized acute brain slices in RIM1α-/- and wild-type mice. In RIM1α-/-, AZs are larger with increased synaptic cleft heights and with a three-fold reduced number of tightly docked SVs (0-2nm). The distance of tightly docked SVs to the AZ center is increased from 110 to 195 nm, and the width of their electron dense material between outer SV membrane and AZ membrane is reduced. Furthermore, the SV pool in RIM1α-/- is more heterogeneous. Thus, RIM1α, beside its role in tight SV docking, is crucial for synaptic architecture and vesicle pool organization in MFBs.
An environmentally responsive transcriptional state modulates cell identities during root development
Authors: Oliva Marina , Stuart Tim , Tang Dave , Pflueger Jahnvi , Poppe Daniel , Jabbari Jafar S. , Gigante Scott , Dragwidge Jonathan Michael , Whelan James , Lewsey Mathew G. , Lister Ryan
Published: March 2022

Roots are fundamental organs for plant development and response to their environment: they anchor the plant to its growth substrate, uptake nutrients and water vital to plant growth, and can sense and respond to a variety of biotic and abiotic stresses. The architecture of root systems and their growth are known to be strongly affected by the environmental conditions found in the soil. However, the acquisition of cell identities at the root meristem is still mainly viewed as ontogenetically driven, where a small number of stem cells generate all the cell types through stereotyped divisions followed by differentiation, along a simple developmental trajectory. The extent to which environmental cues precisely shape and affect these developmental trajectories remains an open question. We used single-cell RNA-seq, combined with spatial mapping, to deeply explore the trajectories of cell states at the tip of Arabidopsis roots, known to contain multiple developing lineages. Surprisingly, we found that most lineage trajectories exhibit a stereotyped bifid topology with two developmental trajectories rather than one. The formation of one of the trajectories is driven by a strong and specific activation of genes involved in the responses to various environmental stimuli, that affects only of a subset of the cells in multiple cell types simultaneously, revealing another layer of patterning of cell identities in the root that is independent of cell ontogeny. We demonstrate the robustness of this environmentally responsive transcriptional state by showing that it is present in a mutant where cell type identities are greatly perturbed, as well as in different Arabidopsis ecotypes. We also show that the root can adapt the proportion of cells that acquire this particular state in response to environmental signals such as nutrient availability. The discovery of this cell state reveals new layers of cell identity that may underpin the adaptive potential of plant development.
Lyophilization induces alterations in cryptococcal exopolysaccharide resulting in reduced antibody binding
Authors: Wear Maggie P. , Hargett Audra A. , Kelly John E. , McConnell Scott A. , Crawford Conor J. , Freedberg Darón I. , Stark Ruth E. , Casadevall Arturo
Published: March 2022

The structural, antigenic, and immunological characterization of microbial polysaccharides requires purification that often involves detergent precipitation and lyophilization. Here we examine physicochemical changes induced by lyophilization on exopolysaccharide (EPS) of the pathogenic fungus Cryptococcus neoformans. Solution 1H NMR reveals significant anomeric signal attenuation following lyophilization of native EPS while 1H ssNMR shows few changes, suggesting diminished molecular motion and consequent broadening of 1H NMR polysaccharide resonances. 13C ssNMR, dynamic light scattering, and transmission electron microscopy show that, while native EPS has rigid molecular characteristics and contains small, loosely packed polysaccharide assemblies, lyophilized and resuspended EPS is disordered and contains larger dense rosette-like aggregates, suggesting that structural water molecules in the interior of the polysaccharide assemblies are removed during extensive lyophilization. Importantly, mAbs to C. neoformans polysaccharide binds the native EPS more strongly than lyophilized EPS. Together, these observations argue for caution when interpreting the biological and immunological attributes of polysaccharides that have been lyophilized to dryness.
Conserved Pib2 regions have distinct roles in TORC1 regulation at the vacuole
Authors: Troutman Kayla K. , Varlakhanova Natalia V. , Tornabene Bryan A. , Ramachandran Rajesh , Ford Marijn G.J.
Published: March 2022

TORC1 is a critical controller of cell growth in eukaryotes. In yeast, the presence of nutrients is signaled to TORC1 by several upstream regulatory sensors that together coordinate TORC1 activity. TORC1 localizes to both vacuolar and endosomal membranes, where differential signaling occurs. This localization is mimicked by Pib2, a key upstream TORC1 regulator that is essential for TORC1 reactivation after nutrient starvation or pharmacological inhibition. Pib2 has both positive and negative effects on TORC1 activity, but the mechanisms remain poorly understood. Here, we pinpoint the Pib2 inhibitory function on TORC1 to residues within short, conserved N-terminal regions. We also show that Pib2 C-terminal regions, helical region E and tail, are essential for TORC1 reactivation. Further, the Pib2 FYVE domain is essential for vacuolar localization, however, it is surprisingly unnecessary for recovery from rapamycin exposure. Using chimeric Pib2 targeting constructs, we show that endosomal localization is not necessary for TORC1 reactivation and cell growth after rapamycin treatment. Thus, a comprehensive molecular dissection of Pib2 demonstrates that each of its conserved regions differentially contribute to Pib2 regulation of TORC1 activity.
Lung injury epigenetically primes mesenchyme for amplified activation upon re-injury
Authors: Jones Dakota L. , Caporarello Nunzia , Meridew Jeffrey A. , Choi Kyoung M. , Haak Andrew J. , Link Patrick A. , Tan Qi , Ordog Tamas , Ligresti Giovanni , Tschumperlin Daniel J.
Published: March 2022

The lungs have a remarkable capacity to repair. However, repetitive injury can lead to progressive fibrosis and end-stage organ failure. Whether tissue-resident mesenchymal cell populations retain epigenetic memory of prior injuries that contribute to this pathological process is unknown. Here we used a genetic lineage labeling approach to mark the lung mesenchyme prior to injury, then performed multi-modal analyses on isolated lung mesenchyme during the initiation, progression and resolution of the fibrotic response. Our results demonstrate the remarkable epigenetic and transcriptional plasticity of the lung mesenchyme during fibrogenic activation and de-activation. Despite this plasticity, we also find that the lung mesenchyme retains specific epigenetic traits (memory) of prior activation, resulting in amplified induction of a fibrogenic program upon re-injury. We identify Runx1 as a critical driver of both fibrogenic activation and epigenetic memory. Comparison of fresh isolated and cultured lung mesenchyme demonstrates that Runx1 is spontaneously activated in standard culture conditions, previously masking these roles of Runx1. Genetic and pharmacological targeting of Runx1 dampens fibrogenic mesenchymal cell activation in cell and tissue models, confirming its functional importance. Finally, publicly available scRNAseq data reveal selective expression of Runx1 in the fibrogenic cell subpopulations that emerge in mouse and human fibrotic lung tissue. Collectively, our findings implicate Runx1 in both the initiation and memory of fibrogenic mesenchymal cell activation that together prime amplified mesenchymal cell responses upon repeated injury.
Multidimensional performance measures and factors and their linkage with performance
Authors: Ahmad Kamilah , Mohamed Zabri Shafie , Atan Siti Anisah
Published: March 2022

Purpose

This study investigates the extent to which performance measures (PMs) are used, the relationship between multidimensional PMs and firm performance and the factors related to firms' PM use.

Design/methodology/approach

The authors surveyed a sample of Malaysian manufacturing firms. Participants responded to a questionnaire indicating their use of PMs, firm performance, level of managerial commitment, degree of environmental uncertainty and firm's use of technology.

Findings

The results indicate a high degree of PM use related to financial indicators, internal efficiency and customer-related metrics. The results also demonstrate that firm performance has significant positive relationships with use of PMs related to quality and customers, efficiency, innovativeness and social responsibility, as well as comprehensive PM use. Industry variation, firm size, technology use and environmental uncertainty are also significantly related to PM use.

Practical implications

Performance measurement systems (PMSs) are an important tool for improving organisational strategy in rapidly changing markets. These findings underscore the significant role of PMSs in manufacturing firms' performance, including emerging economies. The results suggest that individual PMS approaches should align with each firm's evolving needs and the characteristics of the sector and environment in which each firm operates.

Originality/value

This study advances understandings of the contingency approach to PMSs in manufacturing environments.
A framework for fire departments' performance assessment: a systematic literature review
Authors: Komsionchi Eslamzadeh Seyed Milad , Grilo António , Espadinha-Cruz Pedro , Rodrigues João Paulo C. , Lopes José Pedro
Published: March 2022

Purpose

The purpose of this research is to review literature about the performance assessment (PA) in urban fire departments (FDs) to gain state-of-the-art of the fire departments' performance assessment (FDPA) and identify its most applied methods and indicators.

Design/methodology/approach

A five-stage structured literature review (SLR) is conducted to review the FDPA-related studies; then, the statistical analysis is applied to reveal more information from the extracted data and design a general framework for FDPA.

Findings

The systematic literature review resulted in 336 independent variables for FDPA and finding the data envelopment analysis (DEA) as the most applied FDPA method among the mathematical and statistical models in the reviewed papers. By using analysis outcomes, a general conceptual framework for FDPA is proposed.

Research limitations/implications

The reviewed studies were limited to assessments at the strategic level and urban fire protection services.

Practical implications

The results of this research can support fire protection service managers, decision-makers, PA researchers and academicians to have a better understanding of FDPA and state-of-the-art in this field.

Originality/value

A considerable number of studies have been done about the FDPA to provide methods to improve the efficiency and effectiveness of FDs. Although there are reviews about PA in fire service areas, to the best of our knowledge, no study has been done about FDPA.
Overall satisfaction formation across channels: an empirical study
Authors: Bezes Christophe
Published: March 2022

Purpose

No other research analyzes the formation of overall satisfaction across channels, including the reciprocal interactions between store and website satisfaction and the factors that moderate them. Therefore, the aim of the present study is to examine how overall customer satisfaction is formed from the image and perceived congruence of the two main existing channels and the satisfaction induced by each.

Design/methodology/approach

The online study covers 909 customers of a French mortar-to-click retailer specializing in women's and children's clothing. The conceptual model incorporates reciprocal interdependence between store satisfaction and website satisfaction. This model is tested using the procedure specific to non-recursive structural equation model.

Findings

Overall satisfaction with the retailer is not only generated by satisfaction with the store and the website, but also directly and indirectly by the image of each channel. The contribution of the variables depends on the personal and situational characteristics of the customer. Not only is the relationship confirmed from store satisfaction to website satisfaction, but for the first time, in rarer cases the reverse is also observed. On the other hand, while the perceived congruence of channels can improve satisfaction with the channel for certain types of customers, in other cases the congruence can also worsen customers' overall satisfaction.

Research limitations/implications

The detailed analysis of the formation of this satisfaction shows the pre-eminence of the customer over the retailer's initiatives. A retailer may facilitate or encourage virtuous interaction between retailer's channels by making the transfer of information and products more fluid (click and collect for example); but in the end, the customer is the one who decides whether or not to bring the channels closer together.

Originality/value

Contrary to what the literature assumes, in some cases, the retailer's attempt to integrate the channels may even reduce overall satisfaction if customers do not want this integration, just as a high level of satisfaction on the website can reduce in-store satisfaction.
Uncovering the affective affordances of videoconference technologies
Authors: Vidolov Simeon
Published: March 2022

Purpose

The purpose of this study is to examine the role of videoconferencing technologies for mediating and transforming emotional experiences in virtual context.

Design/methodology/approach

Drawing on empirical data of video conferencing experiences, this study identifies different constitutive relations with technology through which actors cope with actual or potential anxieties in virtual meetings. It draws on the phenomenological-existential tradition (Sartre and Merleau-Ponty) and on an interpretive phenomenological analysis (IPA) to conceptualize and illustrate the role of affective affordances in virtual settings.

Findings

The study identifies four different body–technology–other relations that provide different action possibilities, both disclosing and concealing, for navigating emotional experiences in virtual encounters of mutual gazing. These findings offer insights into the anatomy of virtual emotions and provide explanations on the nature of Zoom fatigue (interactive exhaustion) and heightened feelings of self-consciousness resulting from video conferencing interactions.

Originality/value

This paper builds on and extends current scholarship on technological affordances, as well as emotions, to suggest that technologies also afford different tactics for navigating emotional experiences. Thus, this paper proposes the notion of affective affordance that can expand current information system (IS) and organization studies (OS) scholarship in important ways. The focus is on videoconference technologies and meetings that have received little research attention and even less so from a perspective on emotions. Importantly, the paper offers nuanced insights that can advance current research discourse on the relationships between technology, human body and emotions.
Dilemmatic dual-factor determinants of discontinuous intention in cryptocurrency usage
Authors: Huang Cheng-Kui , Lee Neil Chueh-An , Chen Wen-Chi
Published: March 2022

Purpose

Cryptocurrency, an important application of blockchain technology, has gradually circulated, and its use has become widespread. While cryptocurrency is growing rapidly, potential risks are simultaneously emerging. Users thus may abandon their usage behavior of cryptocurrency, hindering the future development of cryptocurrency. While prior studies focus more on the intention to use cryptocurrency in the pre-adoption phase, less studies pay attention to discontinuance usage intention in the post-adoption phase. To fill this knowledge gap, this stfudy aims to explore factors that cause discontinuance usage intention regarding cryptocurrency.

Design/methodology/approach

Based on the net valence framework theoretically grounded on the theory of reason action, a dilemmatic dual-factor model is proposed to figure out cryptocurrency users' discontinuance usage intention from the perceived risk and perceived benefit. This study identifies four potential risks and three potential benefits that affect perceived risk and benefit. The model with nine hypotheses were developed, and research data were collected by a survey method. A total of 343 valid responses were received, and PLS-SEM with SmartPLS was utilized to test the nine hypotheses, with seven hypotheses supported empirically.

Findings

Our findings demonstrate that financial, legal and operational risks are critical to increase users' perceived risk, and perceived usefulness and seamless transactions play important roles in enhancing users' perceived benefit. Moreover, while perceived risk can increase users' discontinuance usage intention to cryptocurrency, perceived benefit can mitigate such intention.

Originality/value

This study contributes nascent knowledge to the literature by examining factors that influence discontinuous usage intention in regard to cryptocurrencies, to firms that have issued or attempted to issue cryptocurrencies and to the potential users of cryptocurrencies by adjusting the mode of operation and investment strategies and reducing user costs, achieving a win-win situation for firms and users.