bluuebunny/crossref_metadata_2025 huggingface dataset:
Political Thought and the Emotion of Shame: John Stuart Mill and the Jamaica Committee during the Governor Eyre Controversy
Authors: Richards Jake Subryan
Published: June 2022

This article argues that the emotion of shame explains how John Stuart Mill and the Jamaica Committee developed intellectual arguments in response to the brutal suppression by Governor Edward Eyre of the Morant Bay rebellion in post-emancipation colonial Jamaica in 1865. Positioning the emotions as integral to cognitive systems, the article traces Mill and the committee's arguments against their opponents, the Eyre Defence Committee. The Jamaica Committee was not solely concerned with liberal imperial order. Instead, under Mill's leadership, the committee sought to reconstruct and defend the pre-rebellion political culture that freedpeople in Jamaica had developed. The committee also demonstrated the illegality of martial law. There were, nonetheless, differences between Mill and other committee members, including Charles Buxton and Frederic Harrison. Shame, the emotion experienced when a subject fails to meet the values to which they are attached, helps to explain these differences. Shame also helped to generate the possibility of reforming the colonial political relationship.
The Big Data Revolution Unlocks New Opportunities for Seismology
Authors: Arrowsmith Stephen , Trugman Daniel , Bergen Karianne , Magnani Beatrice
Published: June 2022

The field of seismology is entering a new era where our understanding of earthquakes and the solid earth is increasingly driven by new Big Data experiments and algorithms.
Mixed Layer Depth Promotes Trophic Amplification on a Seasonal Scale
Authors: Xue Tianfei , Frenger Ivy , Oschlies Andreas , Stock Charles A. , Koeve Wolfgang , John Jasmin G. , Prowe A. E. Friederike
Published: June 2022

The Humboldt Upwelling System is of global interest due to its importance to fisheries, though the origin of its high productivity remains elusive. In regional physical‐biogeochemical model simulations, the seasonal amplitude of mesozooplankton net production exceeds that of phytoplankton, indicating “seasonal trophic amplification.” An analytical approach identifies amplification to be driven by a seasonally varying trophic transfer efficiency due to mixed layer variations. The latter alters the vertical distribution of phytoplankton and thus the zooplankton and phytoplankton encounters, with lower encounters occurring in a deeper mixed layer where phytoplankton are diluted. In global model simulations, mixed layer depth appears to affect trophic transfer similarly in other productive regions. Our results highlight the importance of mixed layer depth for trophodynamics on a seasonal scale with potential significant implications, given mixed layer depth changes projected under climate change.
The Unexpected Oceanic Peak in Energy Input to the Atmosphere and Its Consequences for Monsoon Rainfall
Authors: Ramesh Nandini , Boos William R.
Published: June 2022

Monsoons have historically been understood to be caused by the low thermal inertia of land, allowing more energy from summer insolation to be transferred to the overlying atmosphere than over adjacent ocean. Here, we show that during boreal summer, the global maximum net energy input (NEI) to the atmosphere unexpectedly lies over the Indian Ocean, not over land. Observed radiative fluxes suggest that cloud‐radiative effects (CRE) almost double the NEI over ocean, shifting the NEI peak from land to ocean. Global climate model experiments with both land and interactive sea surface temperatures confirm that CRE create the oceanic NEI maximum. Interactions between CRE, NEI, circulation, and land‐sea contrast in surface heat capacity shift precipitation from Southeast to South Asia. CRE thus alter the global partitioning of precipitation between land and ocean and the spatial structure of Earth's strongest monsoon, in ways that can be understood through the NEI.
Interplate Slip Rate Variation Between Closely Spaced Earthquakes in Southern Mexico: The 2012 Ometepec and 2018 Pinotepa Nacional Thrust Events
Authors: Dominguez L. A. , Taira T. , Cruz‐Atienza V. M. , Iglesias A. , Villafuerte C. , Legrand D. , Pérez‐Campos X. , Raggi M.
Published: June 2022

On 20 March 2012, a Mw 7.5 thrust earthquake started a series of seven large events (7.0 ≤ Mw ≤ 8.2) that struck central Mexico during a period of 9 years (2012–2021). Before this event, the Mexican subduction zone did not experience significant subduction earthquakes (Mw > 7.0) for at least 12 years. Five of the events occurred in the plate interface, resulting in a significantly larger interplate slip rate in the states of Oaxaca and Guerrero. In this study, we explore how an aseismic slip transient caused by the 2012 Mw 7.5 earthquake affected the Oaxaca region and whether this earthquake had a causal relationship with the Mw 7.2 Pinotepa Nacional event that took place six years later in a nerby zone. To this end, we identified and analyzed characteristic repeating earthquakes along the Mexican subduction zone for assessing the plate interface slip history and found a remarkable increase in the aseismic slip rate following the 2012 mainshock, which suggests a long‐standing slip perturbation near the trench in Oaxaca that continued until the Pinotepa Nacional earthquake of 2018.
The effect of Functional Electrical Stimulation-assisted posture-shifting in bone mineral density: case series-pilot study
Authors: Armengol Monica , Zoulias Ioannis D. , Gibbons Robin S. , McCarthy Ian , Andrews Brian J. , Harwin William S. , Holderbaum William
Published: June 2022

Study design

A training intervention study using standing dynamic load-shifting Functional Electrical Stimulation (FES) in a group of individuals with complete spinal cord injury (SCI) T2 to T10.

Objectives

Investigate the effect of FES-assisted dynamic load-shifting exercises on bone mineral density (BMD).

Setting

University Lab within the Biomedical Engineering

Methods

Twelve participants with ASIA A SCI were recruited for this study. Three participants completed side-to-side load-shifting FES-assisted exercises for 29 ± 5 weeks, 2× per week for 1 h, and FES knee extension exercises on alternate days 3× per week for 1 h. Volumetric Bone Mineral density (vBMD) at the distal femur and tibia were assessed using peripheral quantitative computed tomography (pQCT) before and after the intervention study.

Results

Participants with acute and subacute SCI showed an absolute increase of f trabecular vBMD (vBMDTRAB) in the proximal (mean of 26.9%) and distal tibia (mean of 22.35%). Loss of vBMDTRAB in the distal femur was observed.

Conclusion

Improvements in vBMDTRAB in the distal tibia were found in acute and subacute SCI participants, and in the proximal tibia of acute participants, when subjected to anti-gravity FES-assisted load-bearing exercises for 29 ± 5 weeks. No vBMD improvement in distal femur or tibial shaft were observed in any of the participants as was expected. However, improvements of vBMD in the proximal and distal tibia were observed in two participants. This study provides evidence of an improvement of vBMDTRAB, when combining high-intensity exercises with lower intensity exercises 5× per week for 1 h.
Regulatory pathways and drugs associated with ferroptosis in tumors
Authors: Wang Dan , Tang Le , Zhang Yijie , Ge Guili , Jiang Xianjie , Mo Yongzhen , Wu Pan , Deng Xiangying , Li Lvyuan , Zuo Sicheng , Yan Qijia , Zhang Shanshan , Wang Fuyan , Shi Lei , Li Xiayu , Xiang Bo , Zhou Ming , Liao Qianjin , Guo Can , Zeng Zhaoyang , Xiong Wei , Gong Zhaojian
Published: June 2022

Ferroptosis is a type of cell death that depends on iron and reactive oxygen species (ROS). The accumulation of iron and lipid peroxidation primarily initiates oxidative membrane damage during ferroptosis. The core molecular mechanism of ferroptosis includes the regulation of oxidation and the balance between damage and antioxidant defense. Tumor cells usually contain a large amount of H2O2, and ferrous/iron ions will react with excessive H2O2 in cells to produce hydroxyl radicals and induce ferroptosis in tumor cells. Here, we reviewed the latest studies on the regulation of ferroptosis in tumor cells and introduced the tumor-related signaling pathways of ferroptosis. We paid particular attention to the role of noncoding RNA, nanomaterials, the role of drugs, and targeted treatment using ferroptosis drugs for mediating the ferroptosis process in tumor cells. Finally, we discussed the currently unresolved problems and future research directions for ferroptosis in tumor cells and the prospects of this emerging field. Therefore, we have attempted to provide a reference for further understanding of the pathogenesis of ferroptosis and proposed new targets for cancer treatment.
Emerging role of LETM1/GRP78 axis in lung cancer
Authors: Tran Quangdon , Lee Hyunji , Jung Jae Hun , Chang Seung-Hee , Shrestha Robin , Kong Gyeyeong , Park Jisoo , Kim Seon-Hwan , Park Kyu-Sang , Rhee Hyun-Woo , Yun Jeanho , Cho Myung-Haing , Kim Kwang Pyo , Park Jongsun
Published: June 2022

The selective autophagy of damaged mitochondria is called mitophagy. Mitochondrial dysfunction, mitophagy, and apoptosis have been suggested to be interrelated in various human lung carcinomas. Leucine zipper EF-hand-containing transmembrane protein-1 (LETM1) was cloned in an attempt to identify candidate genes for Wolf–Hirschhorn syndrome. LETM1 plays a role in mitochondrial morphology, ion homeostasis, and cell viability. LETM1 has also been shown to be overexpressed in different human cancer tissues, including lung cancer. In the current study, we have provided clear evidence that LETM1 acts as an anchoring protein for the mitochondria-associated ER membrane (MAM). Fragmented mitochondria have been found in lung cancer cells with LETM1 overexpression. In addition, a reduction of mitochondrial membrane potential and significant accumulation of microtubule-associated protein 1 A/1B-light chain 3 punctate, which localizes with Red-Mito, was found in LETM1-overexpressed cells, suggesting that mitophagy is upregulated in these cells. Interestingly, glucose-regulated protein 78 kDa (GRP78; an ER chaperon protein) and glucose-regulated protein 75 kDa (GRP75) were posited to interact with LETM1 in the immunoprecipitated LETM1 of H460 cells. This interaction was enhanced in cells treated with carbonyl cyanide m-chlorophenylhydrazone, a chemical mitophagy inducer. Treatment of cells with honokiol (a GRP78 inhibitor) blocked LETM1-mediated mitophagy, and CRISPR/Cas9-mediated GRP75 knockout inhibited LETM1-induced autophagy. Thus, GRP78 interacts with LETM1. Taken together, these observations support the notion that the complex formation of LETM1/GRP75/GRP78 might be an important step in MAM formation and mitophagy, thus regulating mitochondrial quality control in lung cancer.
Interaction between m6A methylation and noncoding RNA in glioma
Authors: Tao Nairong , Wen Tongxuan , Li Tong , Luan Lan , Pan Hai , Wang Yong
Published: June 2022

Glioma is considered to be the most common brain malignancy in the central nervous system. At present, the aetiology of glioma is not clear. Due to its rapidly growth and easily recurrence, the prognosis of patients with glioma is very poor. N6-methyladenosine (m6A) methylation is an internal reversible modification in most RNAs, including messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). Recent studies have shown that the m6A regulators are abnormal expressed, and are extensively involved in the progression of glioma by targeting ncRNAs. Moreover, as the most important epigenetic regulators, ncRNAs can also affect the function of m6A regulators in glioma. This review summarized the expression and function of certain common m6A regulators in glioma. Also, the current review sum up the mutual interactions between m6A regulators and ncRNAs in glioma.
Embryo-scale epithelial buckling forms a propagating furrow that initiates gastrulation
Authors: Fierling Julien , John Alphy , Delorme Barthélémy , Torzynski Alexandre , Blanchard Guy B. , Lye Claire M. , Popkova Anna , Malandain Grégoire , Sanson Bénédicte , Étienne Jocelyn , Marmottant Philippe , Quilliet Catherine , Rauzi Matteo
Published: June 2022

Cell apical constriction driven by actomyosin contraction forces is a conserved mechanism during tissue folding in embryo development. While much is now understood of the molecular mechanism responsible for apical constriction and of the tissue-scale integration of the ensuing in-plane deformations, it is still not clear if apical actomyosin contraction forces are necessary or sufficient per se to drive tissue folding. To tackle this question, we use the Drosophila embryo model system that forms a furrow on the ventral side, initiating mesoderm internalization. Past computational models support the idea that cell apical contraction forces may not be sufficient and that active or passive cell apico-basal forces may be necessary to drive cell wedging leading to tissue furrowing. By using 3D computational modelling and in toto embryo image analysis and manipulation, we now challenge this idea and show that embryo-scale force balance at the tissue surface, rather than cell-autonomous shape changes, is necessary and sufficient to drive a buckling of the epithelial surface forming a furrow which propagates and initiates embryo gastrulation.
Results of the phase IIa RADICAL trial of the FGFR inhibitor AZD4547 in endocrine resistant breast cancer
Authors: Coombes R. C. , Badman P. D. , Lozano-Kuehne J. P. , Liu X. , Macpherson I. R. , Zubairi I. , Baird R. D. , Rosenfeld N. , Garcia-Corbacho J. , Cresti N. , Plummer R. , Armstrong A. , Allerton R. , Landers D. , Nicholas H. , McLellan L. , Lim A. , Mouliere F. , Pardo O. E. , Ferguson V. , Seckl M. J.
Published: June 2022

We conducted a phase IIa, multi-centre, open label, single arm study (RADICAL; NCT01791985) of AZD4547 (a potent and selective inhibitor of Fibroblast Growth Factor Receptor (FGFR)-1, 2 and 3 receptor tyrosine kinases) administered with anastrozole or letrozole in estrogen receptor positive metastatic breast cancer patients who had become resistant to aromatase inhibitors. After a safety run-in study to assess safety and tolerability, we recruited 52 patients. The primary endpoint was change in tumour size at 12 weeks, and secondary endpoints were to assess response at 6 weeks, 20 weeks and every 8 weeks thereafter and tolerability of the combined treatment. Two partial responses (PR) and 19 stable disease (SD) patients were observed at the 12-week time point. At 28 weeks, according to centrally reviewed Response Evaluation Criteria in Solid Tumours (RECIST) criteria, five PR and 8 SD patients were observed in 50 assessable cases. Overall, objective response rate (5 PR) was of 10%, meeting the pre-specified endpoint. Fourteen patients discontinued due to adverse events. Eleven patients had retinal pigment epithelial detachments which was asymptomatic and reversible in all but one patient. Exploratory ribonucleic acid sequencing (RNA-Seq) analysis was done on patients’ samples: 6 differentially-expressed-genes could distinguish those who benefited from the addition of AZD4547.
Orgo-Seq integrates single-cell and bulk transcriptomic data to identify cell type specific-driver genes associated with autism spectrum disorder
Authors: Lim Elaine T. , Chan Yingleong , Dawes Pepper , Guo Xiaoge , Erdin Serkan , Tai Derek J. C. , Liu Songlei , Reichert Julia M. , Burns Mannix J. , Chan Ying Kai , Chiang Jessica J. , Meyer Katharina , Zhang Xiaochang , Walsh Christopher A. , Yankner Bruce A. , Raychaudhuri Soumya , Hirschhorn Joel N. , Gusella James F. , Talkowski Michael E. , Church George M.
Published: June 2022

Cerebral organoids can be used to gain insights into cell type specific processes perturbed by genetic variants associated with neuropsychiatric disorders. However, robust and scalable phenotyping of organoids remains challenging. Here, we perform RNA sequencing on 71 samples comprising 1,420 cerebral organoids from 25 donors, and describe a framework (Orgo-Seq) to integrate bulk RNA and single-cell RNA sequence data. We apply Orgo-Seq to 16p11.2 deletions and 15q11–13 duplications, two loci associated with autism spectrum disorder, to identify immature neurons and intermediate progenitor cells as critical cell types for 16p11.2 deletions. We further applied Orgo-Seq to identify cell type-specific driver genes. Our work presents a quantitative phenotyping framework to integrate multi-transcriptomic datasets for the identification of cell types and cell type-specific co-expressed driver genes associated with neuropsychiatric disorders.
High-resolution two-dimensional electronic spectroscopy reveals the homogeneous line profile of chromophores solvated in nanoclusters
Authors: Bangert Ulrich , Stienkemeier Frank , Bruder Lukas
Published: June 2022

Doped clusters in the gas phase provide nanoconfined model systems for the study of system-bath interactions. To gain insight into interaction mechanisms between chromophores and their environment, the ensemble inhomogeneity has to be lifted and the homogeneous line profile must be accessed. However, such measurements are very challenging at the low particle densities and low signal levels in cluster beam experiments. Here, we dope cryogenic rare-gas clusters with phthalocyanine molecules and apply action-detected two-dimensional electronic spectroscopy to gain insight into the local molecule-cluster environment for solid and superfluid cluster species. The high-resolution homogeneous linewidth analysis provides a benchmark for the theoretical modelling of binding configurations and shows a promising route for high-resolution molecular two-dimensional spectroscopy.
Factors shaping the abundance and diversity of the gut archaeome across the animal kingdom
Authors: Thomas Courtney M. , Desmond-Le Quéméner Elie , Gribaldo Simonetta , Borrel Guillaume
Published: June 2022

Archaea are common constituents of the gut microbiome of humans, ruminants, and termites but little is known about their diversity and abundance in other animals. Here, we analyse sequencing and quantification data of archaeal and bacterial 16S rRNA genes from 250 species of animals covering a large taxonomic spectrum. We detect the presence of archaea in 175 animal species belonging to invertebrates, fish, amphibians, birds, reptiles and mammals. We identify five dominant gut lineages, corresponding to Methanobrevibacter, Methanosphaera, Methanocorpusculum, Methanimicrococcus and “Ca. Methanomethylophilaceae”. Some archaeal clades, notably within Methanobrevibacter, are associated to certain hosts, suggesting specific adaptations. The non-methanogenic lineage Nitrososphaeraceae (Thaumarchaeota) is frequently present in animal samples, although at low abundance, but may have also adapted to the gut environment. Host phylogeny, diet type, fibre content, and intestinal tract physiology are major drivers of the diversity and abundance of the archaeome in mammals. The overall abundance of archaea is more influenced by these factors than that of bacteria. Methanogens reducing methyl-compounds with H2 can represent an important fraction of the overall methanogens in many animals. Together with CO2-reducing methanogens, they are influenced by diet and composition of gut bacteria. Our results provide key elements toward our understanding of the ecology of archaea in the gut, an emerging and important field of investigation.
Exploring disaster impacts on adaptation actions in 549 cities worldwide
Authors: Nohrstedt Daniel , Hileman Jacob , Mazzoleni Maurizio , Di Baldassarre Giuliano , Parker Charles F.
Published: June 2022

Whether disasters influence adaptation actions in cities is contested. Yet, the extant knowledge base primarily consists of single or small-N case studies, so there is no global overview of the evidence on disaster impacts and adaptation. Here, we use regression analysis to explore the effects of disaster frequency and severity on four adaptation action types in 549 cities. In countries with greater adaptive capacity, economic losses increase city-level actions targeting recently experienced disaster event types, as well as actions to strengthen general disaster preparedness. An increase in disaster frequency reduces actions targeting hazard types other than those that recently occurred, while human losses have few effects. Comparisons between cities across levels of adaptive capacity indicate a wealth effect. More affluent countries incur greater economic damages from disasters, but also have higher governance capacity, creating both incentives and opportunities for adaptation measures. While disaster frequency and severity had a limited impact on adaptation actions overall, results are sensitive to which disaster impacts, adaptation action types, and adaptive capacities are considered.
Enhancement of electrocatalytic oxygen evolution by chiral molecular functionalization of hybrid 2D electrodes
Authors: Liang Yunchang , Banjac Karla , Martin Kévin , Zigon Nicolas , Lee Seunghwa , Vanthuyne Nicolas , Garcés-Pineda Felipe Andrés , Galán-Mascarós José R. , Hu Xile , Avarvari Narcis , Lingenfelder Magalí
Published: June 2022

A sustainable future requires highly efficient energy conversion and storage processes, where electrocatalysis plays a crucial role. The activity of an electrocatalyst is governed by the binding energy towards the reaction intermediates, while the scaling relationships prevent the improvement of a catalytic system over its volcano-plot limits. To overcome these limitations, unconventional methods that are not fully determined by the surface binding energy can be helpful. Here, we use organic chiral molecules, i.e., hetero-helicenes such as thiadiazole-[7]helicene and bis(thiadiazole)-[8]helicene, to boost the oxygen evolution reaction (OER) by up to ca. 130 % (at the potential of 1.65 V vs. RHE) at state-of-the-art 2D Ni- and NiFe-based catalysts via a spin-polarization mechanism. Our results show that chiral molecule-functionalization is able to increase the OER activity of catalysts beyond the volcano limits. A guideline for optimizing the catalytic activity via chiral molecular functionalization of hybrid 2D electrodes is given.
Direct in-water radiation dose measurements using Cherenkov emission corrected signals from polarization imaging for a clinical radiotherapy application
Authors: Cloutier Émily , Beaulieu Luc , Archambault Louis
Published: June 2022

Cherenkov emission (CE) is a visible blueish light emitted in water mediums irradiated by most radiotherapy treatment beams. However, CE is produced anisotropically which currently imposes a geometrical constraint uncertainty for dose measurements. In this work, polarization imaging is proposed and described as a method enabling precise 2D dose measurements using CE. CE produced in a water tank is imaged from four polarization angles using a camera coupled to a rotating polarizer. Using Malus’ law, the polarized component of CE is isolated and corrected with Monte Carlo calculated CE polar and azimuthal angular distributions. Projected dose measurements resulting from polarization-corrected CE are compared to equivalent radiochromic film measurements. Overall, agreement between polarized corrected CE signal and films measurements is found to be within 3%, for projected percent depth dose (PPDD) and profiles at the different tested energies ($$\gamma$$
γ
: 6 and $$18\,\hbox {MV}$$

18

MV

, e$$^{-}$$

-

: 6 and 18$$\,\hbox {MeV}$$

MeV

). In comparison, raw Cherenkov emission presented deviations up 60% for electron beam PPDDs and 20% for photon beams PPDDs. Finally, a degree of linear polarization between 29% and 47% was measured for CE in comparison to $$0.2\pm 0.3$$

0.2
±
0.3

% for scintillation. Hence, polarization imaging is found to be a promising and powerful method for improved radio-luminescent dose measurements with possible extensions to signal separation.
Diversity and distribution of CO2-fixing microbial community along elevation gradients in meadow soils on the Tibetan Plateau
Authors: Feng Haiyan , Wang Zhe , Jia Pengli , Gai Jingping , Chen Baodong , Wang Shikuan
Published: June 2022

Soil CO2-fixing microbes play a significant role in CO2-fixation in the terrestrial ecosystems, particularly in the Tibetan Plateau. To understand carbon sequestration by soil CO2-fixing microbes and the carbon cycling in alpine meadow soils, microbial diversity and their driving environmental factors were explored along an elevation gradient from 3900 to 5100 m, on both east and west slopes of Mila Mountain region on the Tibetan Plateau. The CO2-fixing microbial communities were characterized by high-throughput sequencing targeting the cbbL gene, encoding the large subunit for the CO2-fixing protein ribulose 1, 5-bisphosphate carboxylase/oxygenase. The overall OTU (Operational Taxonomic Unit) abundance is concentrated at an altitude between 4300  and  4900 m. The diversity of CO2-fixing microbes is the highest in the middle altitude area, and on the east slope is higher than those on the west slope. In terms of microbial community composition, Proteobacteria is dominant, and the most abundant genera are Cupriavidus, Rhodobacter, Sulfurifustis and Thiobacillus. Altitude has the greatest influence on the structural characteristics of CO2-fixing microbes, and other environmental factors are significantly correlated with altitude. Therefore, altitude influences the structural characteristics of CO2-fixing microbes by driving environmental factors. Our results are helpful to understand the variation in soil microbial community and its role in soil carbon cycling along elevation gradients.
Geometric property of off resonance error robust composite pulse
Authors: Kukita Shingo , Kiya Haruki , Kondo Yasushi
Published: June 2022

The precision of quantum operations is affected by unavoidable systematic errors. A composite pulse (CP), which has been well investigated in nuclear magnetic resonance (NMR), is a technique that suppresses the influence of systematic errors by replacing a single operation with a sequence of operations. In one-qubit operations, there are two typical systematic errors, Pulse Length Error (PLE) and Off Resonance Error (ORE). Recently, it was found that PLE robust CPs have a clear geometric property. In this study, we show that ORE robust CPs also have a simple geometric property, which is associated with trajectories on the Bloch sphere of the corresponding operations. We discuss the geometric property of ORE robust CPs using two examples.
The relationship between ambivalence towards supervisor's behavior and employee’s mental health
Authors: Herr Raphael M. , Birmingham Wendy C. , van Harreveld Frenk , van Vianen Annelies E. M. , Fischer Joachim E. , Bosch Jos A.
Published: June 2022

Ambivalence in social interactions has been linked to health-related outcomes in private relationships and recent research has started to expand this evidence to ambivalent leadership at the workplace by showing that ambivalent supervisor-employee relationships are related to higher stress levels in employees. However, the mental health consequences of ambivalent leadership have not been examined yet. Using a multilevel approach, this study estimated associations of ambivalent leadership with mental health indicators (depression, anxiety, vital exhaustion, fatigue) in 993 employees from 27 work groups. A total effect of ambivalent leadership was found for all four mental health measures, as well as within-group and between-group effects. The consistent relationships of ambivalent leadership with higher symptoms of mental ill-health at the individual- (i.e., within-group) and the group-level (i.e., between-group) support the existence of an un-confounded association, as well as group effects of collective ambivalence.
FISH improves risk stratification in acute leukemia by identifying KMT2A abnormal copy number and rearrangements
Authors: Li Qinlu , Xing Shugang , Zhang Heng , Mao Xia , Xiao Min , Wang Ying
Published: June 2022

Most cases of acute leukemia (AL) with KMT2A rearrangement (KMT2A-r) have a dismal prognosis. Detection of this aberration in Chinese adult patients relies on reverse transcription polymerase chain reaction (RT-PCR) and chromosome banding analysis (CBA). The fluorescence in situ hybridization (FISH) probe for KMT2A detects KMT2A-r and copy number variation (CNV) but is not routinely used as a detection technique. This study investigated the potential value of FISH in the treatment of AL by performing FISH along with CBA and RT-PCR in 269 de novo cases of AL. The three detection techniques were compared in identification of KMT2A-r, and the applicability of FISH for detecting KMT2A CNV was evaluated. Twenty-three samples were identified as positive for KMT2A-r (20 using FISH, 15 using RT-PCR, 16 using CBA, and eight according to all three). FISH also identified 17 KMT2A CNV, 15 with gains and two with deletions. Ten patients with acute myeloid leukemia (AML) harboring KMT2A CNV had a complex karyotype, a negative prognostic factor in AML. Adding FISH of KMT2A to routine detection leads to more accurate detection of KMT2A-r and improved identification of KMT2A CNV, which would benefit patients by improving the risk stratification in AL.
Live imaging-based assay for visualising species-specific interactions in gamete adhesion molecules
Authors: Nakajima Kohdai P. , Valansi Clari , Kurihara Daisuke , Sasaki Narie , Podbilewicz Benjamin , Higashiyama Tetsuya
Published: June 2022

Successful gamete fusion requires species-specific membrane adhesion. However, the interaction of adhesion molecules in gametes is difficult to study in real time through low-throughput microscopic observation. Therefore, we developed a live imaging-based adhesion molecule (LIAM) assay to study gamete adhesion molecule interactions in cultured cells. First, we modified a fusion assay previously established for fusogens introduced into cultured cells, and confirmed that our live imaging technique could visualise cell–cell fusion in the modified fusion assay. Next, instead of fusogen, we introduced adhesion molecules including a mammalian gamete adhesion molecule pair, IZUMO1 and JUNO, and detected their temporal accumulation at the contact interfaces of adjacent cells. Accumulated IZUMO1 or JUNO was partly translocated to the opposite cells as discrete spots; the mutation in amino acids required for their interaction impaired accumulation and translocation. By using the LIAM assay, we investigated the species specificity of IZUMO1 and JUNO of mouse, human, hamster, and pig in all combinations. IZUMO1 and JUNO accumulation and translocation were observed in conspecific, and some interspecific, combinations, suggesting potentially interchangeable combinations of IZUMO1 and JUNO from different species.
Neuroimaging and cognitive correlates of retinal Optical Coherence Tomography (OCT) measures at late middle age in a twin sample
Authors: Moran Chris , Xu Zheng Yang , Mehta Hemal , Gillies Mark , Karayiannis Chris , Beare Richard , Chen Christine , Srikanth Velandai
Published: June 2022

Sharing in embryology and function between the eye and brain has led to interest in whether assessments of the eye reflect brain changes seen in neurodegeneration. We aimed to examine the associations between measures of retinal layer thickness using optical coherence tomography (OCT) and multimodal measures of brain structure and function. Using a convenient sample of twins discordant for type 2 diabetes, we performed cognitive testing, structural brain MRI (tissue volumetry), diffusion tensor imaging (white matter microstructure), and arterial spin labelling (cerebral blood flow). OCT images were recorded and retinal thickness maps generated. We used mixed level modelling to examine the relationship between retinal layer thicknesses and brain measures. We enrolled 35 people (18 pairs, mean age 63.8 years, 63% female). Ganglion cell layer thickness was positively associated with memory, speed, gray matter volume, and altered mean diffusivity. Ganglion cell layer thickness was strongly positively associated with regional cerebral blood flow. We found only a limited number of associations between other retinal layer thickness and measures of brain structure or function. Ganglion cell layer thickness showed consistent associations with a range of brain measures suggesting it may have utility as a marker for future dementia risk.
MIF homolog d-dopachrome tautomerase (D-DT/MIF-2) does not inhibit accumulation and toxicity of misfolded SOD1
Authors: Alaskarov Amina , Barel Shir , Bakavayev Shamchal , Kahn Joy , Israelson Adrian
Published: June 2022

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of upper and lower motor neurons. About 20% of familial ALS cases are caused by dominant mutations in SOD1. It has been suggested that toxicity of mutant SOD1 results from its misfolding, however, it is unclear why misfolded SOD1 accumulates within specific tissues. We have demonstrated that macrophage migration inhibitory factor (MIF), a multifunctional protein with cytokine/chemokine and chaperone-like activity, inhibits the accumulation and aggregation of misfolded SOD1. Although MIF homolog, D-dopachrome tautomerase (D-DT/MIF-2), shares structural and genetic similarities with MIF, its biological function is not well understood. In the current study, we investigated, for the first time, the mechanism of action of D-DT in a model of ALS. We show that D-DT inhibits mutant SOD1 amyloid aggregation in vitro, promoting the formation of amorphous aggregates. Moreover, we report that D-DT interacts with mutant SOD1, but does not inhibit misfolded mutant SOD1 accumulation and toxicity in neuronal cells. Finally, we show that D-DT is expressed mainly in liver and kidney, with extremely low expression in brain and spinal cord of adult mice. Our findings contribute to better understanding of D-DT versus MIF function in the context of ALS.
Deficits in spontaneous and stimulus-dependent retrieval as an early sign of abnormal aging
Authors: Wereszczyński Michał , Niedźwieńska Agnieszka
Published: June 2022

Research on early cognitive markers of Alzheimer’s disease is primarily focused on episodic memory tests that involve deliberate retrieval. Our purpose was to provide clear evidence to support a novel Spontaneous Retrieval Deficit hypothesis, which predicts that people at pre-clinical stages of dementia, including those with amnestic Mild Cognitive Impairment (aMCI), are particularly impaired on tasks based on spontaneous retrieval. We compared 27 aMCI individuals and 27 healthy controls on mind-wandering while performing a task during which there were exposed to either highly meaningful or unmeaningful pictures. The substantial reduction in mind-wandering among individuals with aMCI was found with exposure to highly meaningful stimuli, but not to unmeaningful pictures, and it was most pronounced for past-oriented thoughts, i.e., involuntary autobiographical memories. Those findings provide strong support for this novel hypothesis, and show that it is the spontaneous, but bottom-up and cue-driven processes, for which meaningful environmental stimuli are crucial, that are very promising early markers of the disease.
Mirror-image streptavidin with specific binding to L-biotin, the unnatural enantiomer
Authors: Suganuma Masatoshi , Kubo Takuya , Ishiki Kengo , Tanaka Kota , Suto Kouzou , Ejima Daisuke , Toyota Masahiro , Tsumoto Kouhei , Sato Toshiyuki , Nishikawa Youichi
Published: June 2022

The streptavidin–biotin system is known to have a very high affinity and specificity and is widely used in biochemical immunoassays and diagnostics. However, this method is affected by endogenous D-biotin in serum sample measurements (biotin interference). While several efforts using alternative high-affinity binding systems (e.g., genetically modified streptavidin and biotin derivatives) have been attempted, these efforts have all led to reduction in affinity. To solve this interference issue, the enantiomer of streptavidin was synthesized, which enabled specific binding to L-biotin. We successfully obtained a functional streptavidin molecule by peptide synthesis using D-amino acids and an in vitro folding technique. Several characterizations, including size exclusion chromatography (SEC), circular dichroism spectra (CD), and heat denaturation experiments collectively confirmed the higher-order enantiomer of natural streptavidin had been formed with comparable stability to the natural protein. L-biotin specific binding of this novel molecule enabled us to avoid biotin interference in affinity measurements using the Biacore system and enzyme-linked immunosorbent assay (ELISA). We propose the enantiomer of streptavidin as a potential candidate to replace the natural streptavidin–biotin system, even for in vivo use.
Comparative clinical and radiographic outcomes between early and delayed wrist mobilization after volar fixed-angle plate fixation of distal radius fracture
Authors: Laohaprasitiporn Panai , Boonchai Kitidate , Monteerarat Yuwarat , Limthongthang Roongsak , Vathana Torpon
Published: June 2022

Postoperative immobilization protocols after volar fixed-angle plate fixation of distal radius fractures (DRF) vary among surgeons. This study aimed to compare functional outcomes, radiographic parameters, and complications between early and delayed mobilization after volar fixed-angle plate fixation of DRF. This study is a randomized controlled trial. The early group was allowed to perform wrist motion exercise immediately after surgery and the delayed group was allowed to perform it after 2 weeks of external immobilization. Postoperative patient-rated wrist evaluation (PRWE), disabilities of arm, shoulder, and hand (DASH), wrist range of motion, visual analog scale (VAS) pain score, and grip strength were evaluated. Forty-eight patients with DRF were enrolled and randomly allocated to the early or delayed mobilization groups. The PRWE, DASH, VAS pain score, grip strength, and wrist motion of both groups significantly improved over time. However, there were no significant differences between groups at any timepoint. Radiographic parameters were not different between groups. There were no significant differences in functional outcomes, radiographic parameters, and complications between early and delayed mobilization after volar fixed-angle plate of DRF. Immediate postoperative wrist range-of-motion exercise can be safely initiated after volar fixed-angle plate fixation of DRF without external immobilization.

Clinical trial registration: Thaiclinicaltrials.org identifier: TCTR20180927005. Registered 27/09/2018—retrospectively registered. https://www.thaiclinicaltrials.org/show/TCTR20180927005.
In vitro evaluation of the effects of different particle types in toothpastes on the efficacy against enamel erosion and wear
Authors: Fischer Melanie , Schlueter Nadine , Rupf Stefan , Ganss Carolina
Published: June 2022

The effects of the particle fraction in toothpastes in the context of erosion and erosive tooth wear has not been fully elucidated. Thus, aim of this study was to investigate experimental toothpastes, each with one specific particle type. Toothpastes with seven different types of silica or alumina were prepared as slurry either with or without active ingredients (NaF or F/Sn). Human enamel samples were exposed to a cyclic erosion/abrasion model, and were either treated with the respective slurries only or additionally brushed in a brushing machine. Tissue loss was profilometrically monitored. After treatment with slurries without active ingredients or with NaF, tissue loss increased significantly within groups over time (p < 0.001 each). At the end of the trial, there were minor differences between groups (not exceeding 10–20%; p > 0.05 for most comparisons). After treatment with the F/Sn slurries, tissue loss stagnated completely over time, with the exception of one silica type and alumina, but both still reduced tissue loss by 40–50% (compared to control p < 0.001 each). Relative to the type of the active ingredient, the particle type seems to be a secondary factor for the efficacy of toothpastes on erosion and erosive tooth wear in enamel.
Investigating the ligand agonism and antagonism at the D2long receptor by dynamic mass redistribution
Authors: Forster Lisa , Pockes Steffen
Published: June 2022

The signalling of the D2 receptor (D2R), a G protein-coupled receptor (GPCR), is a complex process consisting of various components. For the screening of D2R ligands, methods quantifying distinct second messengers such as cAMP or the interaction of the receptor with β-arrestin, are commonly employed. In contrast, a label-free biosensor technology like dynamic mass redistribution (DMR), where it is mostly unknown how the individual signalling pathways contribute to the DMR signal, provides a holistic readout of the complex cellular response. In this study, we report the successful application of the DMR technology to CHO-K1 cells stably expressing the human dopamine D2long receptor. In real-time kinetic experiments, studies of D2R reference compounds yielded results for agonists and antagonists that were consistent with those obtained by conventional methods and also allowed a discrimination between partial and full agonists. Furthermore, investigations on the signalling pathway in CHO-K1 hD2longR cells identified the Gαi/o protein as the main proximal trigger of the observed DMR response. The present study has shown that the DMR technology is a valuable method for the characterisation of putative new ligands and, due to its label-free nature, suggests its use for deorphanisation studies of GPCRs.
Fostering eating after stroke (FEASt) trial for improving post-stroke dysphagia with non-invasive brain stimulation
Authors: Kumar Sandeep , Marchina Sarah , Langmore Susan , Massaro Joseph , Palmisano Joseph , Wang Na , Searls David Eric , Lioutas Vasileios , Pisegna Jessica , Wagner Cynthia , Shinde Anant , Schlaug Gottfried
Published: June 2022

Dysphagia is a serious stroke complication but lacks effective therapy. We investigated safety and preliminary efficacy of anodal transcranial direct current stimulation (atDCS) paired with swallowing exercises in improving post-stroke dysphagia from an acute unilateral hemispheric infarction (UHI). We conducted a double-blind, early phase-2 randomized controlled trial, in subjects (n = 42) with moderate-severe dysphagia [Penetration and Aspiration Scale (PAS) score ≥ 4], from an acute-subacute UHI. Subjects were randomized to Low-Dose, High-Dose atDCS or Sham stimulation for 5 consecutive days. Primary safety outcomes were incidence of seizures, neurological, motor, or swallowing function deterioration. Primary efficacy outcome was a change in PAS scores at day-5 of intervention. Main secondary outcome was dietary improvement at 1-month, assessed by Functional Oral Intake (FOIS) score. No differences in pre-defined safety outcomes or adjusted mean changes in PAS, FOIS scores, between groups, were observed. Post-hoc analysis demonstrated that 22 /24 subjects in the combined atDCS group had a clinically meaningful dietary improvement (FOIS score ≥ 5) compared to 8 /14 in Sham (p = 0.037, Fisher-exact). atDCS application in the acute-subacute stroke phase is safe but did not decrease risk of aspiration in this early phase trial. The observed dietary improvement is promising and merits further investigation.
Amygdala–pons connectivity is hyperactive and associated with symptom severity in depression
Authors: Wong Jing Jun , Wong Nichol M. L. , Chang Dorita H. F. , Qi Di , Chen Lin , Lee Tatia M. C.
Published: June 2022

Knowledge of the neural underpinnings of processing sad information and how it differs in people with depression could elucidate the neural mechanisms perpetuating sad mood in depression. Here, we conduct a 7 T fMRI study to delineate the neural correlates involved only in processing sad information, including pons, amygdala, and corticolimbic regions. We then conduct a 3 T fMRI study to examine the resting-state connectivity in another sample of people with and without depression. Only clinically depressed people demonstrate hyperactive amygdala–pons connectivity. Furthermore, this connectivity is related to depression symptom severity and is a significant indicator of depression. We speculate that visual sad information reinforces depressed mood and stimulates the pons, strengthening the amygdala–pons connectivity. The relationship between this connectivity and depressive symptom severity suggests that guiding one’s visual attention and processing of sad information may benefit mood regulation.
Dynamic full-field optical coherence tomography allows live imaging of retinal pigment epithelium stress model
Authors: Groux Kassandra , Verschueren Anna , Nanteau Céline , Clémençon Marilou , Fink Mathias , Sahel José-Alain , Boccara Claude , Paques Michel , Reichman Sacha , Grieve Kate
Published: June 2022

Retinal degenerative diseases lead to the blindness of millions of people around the world. In case of age-related macular degeneration (AMD), the atrophy of retinal pigment epithelium (RPE) precedes neural dystrophy. But as crucial as understanding both healthy and pathological RPE cell physiology is for those diseases, no current technique allows subcellular in vivo or in vitro live observation of this critical cell layer. To fill this gap, we propose dynamic full-field OCT (D-FFOCT) as a candidate for live observation of in vitro RPE phenotype. In this way, we monitored primary porcine and human stem cell-derived RPE cells in stress model conditions by performing scratch assays. In this study, we quantified wound healing parameters on the stressed RPE, and observed different cell phenotypes, displayed by the D-FFOCT signal. In order to decipher the subcellular contributions to these dynamic profiles, we performed immunohistochemistry to identify which organelles generate the signal and found mitochondria to be the main contributor to D-FFOCT contrast. Altogether, D-FFOCT appears to be an innovative method to follow degenerative disease evolution and could be an appreciated method in the future for live patient diagnostics and to direct treatment choice.
The INSIDEOUT framework provides precise signatures of the balance of intrinsic and extrinsic dynamics in brain states
Authors: Deco Gustavo , Sanz Perl Yonatan , Bocaccio Hernan , Tagliazucchi Enzo , Kringelbach Morten L.
Published: June 2022

Finding precise signatures of different brain states is a central, unsolved question in neuroscience. We reformulated the problem to quantify the ‘inside out’ balance of intrinsic and extrinsic brain dynamics in brain states. The difference in brain state can be described as differences in the detailed causal interactions found in the underlying intrinsic brain dynamics. We used a thermodynamics framework to quantify the breaking of the detailed balance captured by the level of asymmetry in temporal processing, i.e. the arrow of time. Specifically, the temporal asymmetry was computed by the time-shifted correlation matrices for the forward and reversed time series, reflecting the level of non-reversibility/non-equilibrium. We found precise, distinguishing signatures in terms of the reversibility and hierarchy of large-scale dynamics in three radically different brain states (awake, deep sleep and anaesthesia) in electrocorticography data from non-human primates. Significantly lower levels of reversibility were found in deep sleep and anaesthesia compared to wakefulness. Non-wakeful states also showed a flatter hierarchy, reflecting the diversity of the reversibility across the brain. Overall, this provides signatures of the breaking of detailed balance in different brain states, perhaps reflecting levels of conscious awareness.