bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAYSD1 senses UFMylated ribosome to safeguard co-translational protein translocation at the endoplasmic reticulum
Authors: Wang Lihui , Xu Yue , Yun Sijung , Yuan Quan , Satpute-Krishnan Prasanna , Ye Yihong 
Published: December 2022

AbstractTranslocon clogging at the endoplasmic reticulum (ER) as a result of translation stalling triggers ribosome UFMylation, activating aTranslocation-AssociatedQualityControl (TAQC) mechanism that degrades clogged substrates. How cells sense ribosome UFMylation to initiate TAQC is unclear. Here we use a genome-wide CRISPR/Cas9 screen to identify an uncharacterized membrane protein named SAYSD1 that facilitates TAQC. SAYSD1 associates with the Sec61 translocon, and also recognizes both ribosome and UFM1 directly, engaging a stalled nascent chain to ensure its transport via the TRAPP complex to lysosomes for degradation. Like UFM1 deficiency, SAYSD1 depletion causes the accumulation of translocation-stalled proteins at the ER and triggers ER stress. Importantly, disrupting UFM1- and SAYSD1-dependent TAQC inDrosophilaleads to intracellular accumulation of translocation-stalled collagens, defective collagen deposition, abnormal basement membranes, and reduced stress tolerance. Together, our data support a model that SAYSD1 acts as a UFM1 sensor that collaborates with ribosome UFMylation at the site of clogged translocon, safeguarding ER homeostasis during animal development.
Visualizing somatic alterations in spatial transcriptomics data of skin cancer
Authors: Chen Limin , Chang Darwin , Tandukar Bishal , Deivendran Delahny , Cho Raymond , Cheng Jeffrey , Bastian Boris C. , Ji Andrew L. , Shain A. Hunter 
Published: December 2022

AbstractTools to visualize genetic alterations within tissues remain underdeveloped despite the growth of spatial transcriptomic technologies, which measure gene expression in different regions of tissues. Since genetic alterations can be detected in RNA-sequencing data, we explored the feasibility of observing somatic alterations in spatial transcriptomics data. Extracting genetic information from spatial transcriptomic data would illuminate the spatial distribution of clones and allow for correlations with regional changes in gene expression to support genotype-phenotype studies. Recent work demonstrates that copy number alterations can be inferred from spatial transcriptomics data1. Here, we describe new software to further enhance the inference of copy number from spatial transcriptomics data. Moreover, we demonstrate that single nucleotide variants are also detectable in spatial transcriptomic data. We applied these approaches to map the location of point mutations, copy number alterations, and allelic imbalances in spatial transcriptomic data of two cutaneous squamous cell carcinomas. We show that both tumors are dominated by a single clone of cells, suggesting that their regional variations in gene expression2are likely driven by non-genetic factors. Furthermore, we observe mutant cells in histologically normal tissue surrounding one tumor, which were not discernible upon histopathologic evaluation. Finally, we detected mono-allelic expression of immunoglobulin heavy chains in B-cells, revealing clonal populations of plasma cells surrounding one tumor. In summary, we put forward solutions to add the genetic dimension to spatial transcriptomic datasets, augmenting the potential of this new technology.
Stat3 has a different role in axon growth during development than it does in axon regeneration after injury
Authors: Duan Qinwen , Zheng Hongfei , Qin Yanjun , Yan Jizhou , Burgess Shawn , Wang Jian , Fan Chunxin 
Published: December 2022

AbstractSignal transducer and activator of transcription 3 (STAT3) is essential for neural development and regeneration as a key transcription factor and mitochondrial activator. In this study, using zebrafish posterior lateral line (PLL) axons, we demonstrate that Stat3 plays distinct roles in PLL axon embryonic growth and regeneration. In zebrafishstat3mutants the PLL axons were truncated during embryonic growth. Expressingstat3in neurons of the PLL ganglion rescued their axon growth suggestingstat3promoted PLL axon growth in a cell-autonomous manner. Using Jak/Stat signaling inhibitors or modified Stat3, we found Jak/Stat signaling was dispensable for PLL axon growth. We showed that Stat3 was co-localized with mitochondria in PLL axon and lower ATPase activity instat3mutant embryos than wild-type embryos. The PLL axon growth was affected by mitochondrial modulators indicating that Stat3 regulated PLL axon growth through mitochondrial Stat3 function. Mutation ofstat3or treating with Jak/Stat signaling inhibitors retarded PLL axon regeneration and Schwann cell migration. Taken together, Stat3 is required for embryonic PLL axon growth by regulating the ATP synthesis efficiency of mitochondria, whereas Stat3 stimulates PLL axon regeneration through regulating Schwann cell migration via Jak/Stat signaling. Our findings show a new mechanism of Stat3 in axon growth and regeneration.Author SummaryNeurons are one of the most specialized cell type in our body. A slender axon used for transmitting information between neuron and target cell extends from the cell body. Axon extension during both development and regeneration is regulated by intrinsic and extrinsic factors. In this study, we used the zebrafish posterior lateral line (PLL) axons which extends a long distance to study the regulation of axon extension. Signal transducer and activator of transcription 3 (STAT3) is a key transcription factor in Jak/Stat signaling and an activator for mitochondria functions. Our results demonstrate that Stat3 plays distinct roles in PLL axons development and regeneration. During embryonic development, Jak/Stat signaling is dispensable for PLL axons extension, whereas the mitochondrial Stat3 is required for embryonic axon growth through promoting ATP synthesis. During PLL axons regeneration, Jak/Stat is essential for Schwann cells migration which mediates axon regeneration.
Convergent deployment of ancestral programs during the evolution of mammalian flight membranes
Authors: Feigin Charles Y. , Moreno Jorge A. , Ramos Raul , Mereby Sarah A. , Alivisatos Ares , Wang Wei , van Amerongen Renée , Camacho Jasmin , Rasweiler John J. , Behringer Richard R. , Ostrow Bruce , Plikus Maksim V. , Mallarino Ricardo 
Published: December 2022

AbstractLateral flight membranes, or patagia, have evolved repeatedly in diverse mammalian lineages. While little is known about patagium development, its recurrent evolution may suggest a shared molecular basis. By combining transcriptomics, developmental experiments, and mouse transgenics, we demonstrate that lateral WNT5A expression in the marsupial sugar glider (Petaurus breviceps) promotes the differentiation of its patagium primordium. We further show that this function of WNT5A reprises ancestral roles in skin morphogenesis predating mammalian flight and has been convergently employed during patagium evolution in eutherian bats. Moreover, we find that many genes involved in limb development have been re-deployed during patagium outgrowth in both the sugar glider and bat. Taken together, our findings reveal that deeply conserved molecular toolkits underpin the evolutionary transition to flight in mammals.
Histone monoaminylation dynamics are regulated by a single enzyme and promote neural rhythmicity
Authors: Zheng Qingfei , Bastle Ryan M. , Zhao Shuai , Kong Lingchun , Vostal Lauren , Ramakrishnan Aarthi , Shen Li , Fulton Sasha L. , Wang Haifeng , Zhang Baichao , Upad Akhil , Dierdorff Lauren , Thompson Robert E. , Molina Henrik , Stransky Stephanie , Sidoli Simone , Muir Tom W. , Li Haitao , David Yael , Maze Ian 
Published: December 2022

ABSTRACTHistone H3 monoaminylations at glutamine(Q) 5 represent an important family of epigenetic markers in neurons that play critical roles in the mediation of permissive gene expression (1, 2). We previously demonstrated that H3Q5 serotonylation(ser) and dopaminylation(dop) are catalyzed by the Transglutaminase 2 (TGM2) enzyme and alter both local and global chromatin states (3, 4). Here, we found that TGM2 additionally functions as an “eraser” of H3 monoaminylations that is capable of “re-writing” these epigenetic marks in cells, including a new class of this modification, H3Q5 histaminylation(his), which displays dynamic diurnal expression in brain and contributes to neural rhythmicity. We found that H3Q5his inhibits binding of the MLL1 complex to the H3 N-terminus and attenuates its methyltransferase activity on H3 lysine(K) 4. We determined that H3Q5 monoaminylation dynamics are dictated by local monoamine concentrations, which are utilized by TGM2. Taken together, we present here a novel mechanism through which a single chromatin regulatory enzyme is capable of sensing chemical microenvironments to affect the epigenetic states of cells.One sentence summaryA single enzyme, TGM2, bidirectionally controls H3 monoaminylation dynamics, which, in turn, facilitate neural rhythmicity.
Asymmetric effect of renewable energy consumption and economic growth on environmental degradation in sub-Saharan Africa
Authors: Abdul-Mumuni Abdallah , Mensah Barbara Deladem , Amankwa Fosu Richard 
Published: December 2022

PurposeWhile there are enormous studies on the determinants of environmental degradation, empirical studies on the effect of renewable energy consumption and economic growth on the environment remain limited. The purpose of this paper is to examine the asymmetric effect of renewable energy consumption and economic growth on environmental degradation in 31 selected sub-Saharan African countries spanning from 1990 to 2018.Design/methodology/approachTo examine possible asymmetric effects of the exogenous variables on environmental degradation, we used the panel nonlinear autoregressive distributed lag approach and secondary data was sourced from the World Bank (2021).FindingsThe cointegration test results suggest that there is a long-run cointegration among the variables whereas our main findings indicate that environmental degradation responds asymmetrically to changes in renewable energy consumption and economic growth. The results further reveal that both positive and negative shocks in renewable energy consumption reduce environmental degradation. On the other hand, positive and negative shocks in economic growth increase environmental degradation in the long run.Research limitations/implicationsThe implications of this study include the need for policymakers in sub-Saharan Africa to encourage the utilization of renewable energy as it reduces environmental degradation. Also, governments in the subregion should gradually replace the usage of fossil fuels by adapting renewable energy sources so as to achieve higher economic growth.Originality/valueThe positive and negative shocks of renewable energy consumption and economic growth on environmental degradation are examined to ascertain their asymmetric relationships.
Green knowledge management and organizational green culture: an interaction for organizational green innovation and green performance
Authors: Abbas Jawad , Khan Shumaila Mazhar 
Published: December 2022

PurposeBased on the sharp decline in the quantity and quality of natural resources, many organizations are shifting their operations to an eco-friendly system. However, this objective cannot be achieved without capitalizing on green knowledge and innovation. The purpose of this study is to examine whether green knowledge management (GKM) strengthens organizational green innovation capabilities, leading to green performance. Moreover, considering culture as the buffering condition, the authors took it as the conditional boundary between GKM and green innovation and investigated if it impacts their relationship.Design/methodology/approachThe authors focused on the manufacturing and services firms’ managerial and non-managerial staff and collected data following the non-probability convenience sampling technique. The collected data were examined through structural equation modeling.FindingsIt is found that GKM is a significant positive predictor of organizational green innovation and green performance and strengthens their abilities in these areas. However, green innovation partially mediates between GKM and corporate green performance. It is also found that green culture strengthens the relationship between GKM and organizational green innovation.Originality/valueThis study’s findings provide confidence to organizational managers and related stakeholders to achieve sustainability goals by capitalizing on GKM and promoting green culture in their setup. This study is also among the pioneer studies investigating GKM as a unified system and linking it with environmental performance domains.
B‐cell targeted therapy of pemphigus
Authors: Yamagami Jun 
Published: December 2022

AbstractPemphigus is an autoimmune disease that causes blistering and erosion of the skin and mucous membranes because of autoantibodies against desmoglein, which plays an important role in adhesion between epidermal keratinocytes. Treatment of pemphigus has long been centered on corticosteroids, and the guidelines for management of pemphigus have recommended high‐dose systemic corticosteroids as the first‐line treatment. While guideline‐based treatment has been shown to be beneficial in patients with pemphigus, it has also become clear that this treatment is accompanied by significant burden and risk. The challenge for future pemphigus treatment is to maximize efficacy while minimizing risk during the course of the disease. In this regard, treatment targeting B cells is expected to become increasingly important as autoreactive B cells in pemphigus patients are thought to play a major role in the production of autoantibodies, which form the basis of the pathogenesis. The recent expansion of insurance coverage to rituximab, a monoclonal antibody against CD20, for refractory pemphigus in the USA, Europe, and Japan has opened up a new era of pemphigus treatment by enabling treatment strategies with drugs targeting B cells in patients. Here, we discuss the current status and future prospects of pemphigus treatment, focusing on rituximab and Bruton's tyrosine kinase inhibitors, which are expected to become essential drugs for pemphigus treatment in the future.
Age and support for public debt reduction
Authors: ASPIDE ALESSIA , BROWN KATHLEEN J. , DIGIUSEPPE MATTHEW , SLASKI ALEXANDER 
Published: December 2022

AbstractMany scholars and policymakers see rising debt burdens in the industrialised world as the product of ageing populations. Prominent theoretical models of government debt accumulation – used to justify fiscal rules and austerity measures – explicitly assume that support for debt reduction decreases with age. While such models have been influential, the fundamental relationship between age and preferences for debt has not been tested empirically. We test this argument but further theorise that the relationship between age and debt preferences is non‐linear. While the elderly have a clear preference for ignoring debt burdens, we add that the young should also prefer to delay reckoning with high national debts given their low income and expectations of higher future earnings. Using survey data (N = 112,689), we find that age does have a small to modest non‐linear impact on concern for national deficits and debt burdens. Middle‐aged respondents are most concerned about debt reduction, while the young and old view reducing government debt as less of a policy priority. Notably, the relationship is strongest in countries with more generous old‐age benefits.
Catheter‐directed thrombolysis for lower limb ischaemia: A retrospective study of treatment outcomes
Authors: Parker Sophie , Midgley David John , Iosua Ella , Galletly Anna , Durran Alexandra , Lau Gabriel , Reddy Michael , Abcarian Peter , Letts James 
Published: December 2022

AbstractIntroductionLower limb ischaemia secondary to occlusion of a lower limb artery is a limb‐threatening condition that can be effectively treated by catheter‐directed thrombolysis (CDT). The purpose of this study was to examine treatment outcomes of CDT both at the time of treatment and ongoing patency up to 12 months following treatment. The secondary aim of the study was to investigate the influence of age of occlusion and treatment duration on success and complication rates.MethodA retrospective observational study was performed at a single institution over a 10‐year period from 2010 to 2019. Data for patient demographics, vessel occlusion factors and treatment information were obtained and analysed. Patency data were investigated using Kaplan–Meier analyses.ResultsA total of 218 limbs in 159 patients were treated during the study period. The aetiology of vessel occlusion was in situ thrombosis or occluded bypass graft in 74.5%. Technical success was achieved in 55.5% with CDT alone and 84.4% by using CDT in combination with adjunctive endovascular procedures (angioplasty or stenting). The overall probability of patency was 0.65 at 3 months and 0.44 at 12 months. The overall rate of major amputation within 30 days of thrombolysis was 8.2%. Thirty‐day mortality was 6.3% and was secondary to intracranial haemorrhage in three patients.ConclusionTechnical success of CDT was found to be significantly higher when combined with adjunctive endovascular procedures at the time of CDT. Despite an initial moderate technical success, the probability of patency at 12 months was only 44%. The likelihood of bleeding complications and technical and long‐term success remain key considerations when selecting patients for CDT.
Remembering Fraud in the Future: Investigating and Improving Auditors' Attention to Fraud during Audit Testing*
Authors: Austin Ashley A. 
Published: December 2022

ABSTRACTDuring the testing stages of the audit, auditors must divide their attention simultaneously between (i) performing the planned audit procedures and (ii) remaining broadly skeptical and alert for fraud. Regulators note instances in which auditors do not take actions that effectively respond to fraud risks during these later stages, suggesting auditors may devote insufficient attention to fraud while they are busy executing the planned audit procedures. Leveraging prospective memory theory, I identify and test an intervention that can improve auditors' attention to fraud by encouraging auditors to have implementation intentions—that is, more detailed plans about when and how they will consider fraud. I find that encouraging implementation intentions interacts with auditors' perceived fraud task importance to increase auditors' attention to fraud when this attention would otherwise be lower, making auditors more likely to take effective fraud actions. Importantly, these results also indicate that, even in a high fraud risk setting, auditors may devote insufficient attention to fraud while performing the planned audit procedures, confirming concerns voiced by regulators. However, my study also highlights concerns about regulators' inspection processes prompting auditors to focus too heavily on inspection risk, as the results suggest auditors are less likely to detect fraud in high‐risk audit areas thought to have low inspection risk.
Impacts of relatively rational and irrational investor sentiment on realized volatility
Authors: Tseng Tseng‐Chan , Lai Hung‐Cheng , Chen Jih‐Kuang 
Published: December 2022

AbstractWe adopt intraday data in this study to facilitate an exploration of the influences of relatively rational and irrational investor sentiment on volatility within the Taiwan stock markets. Following the decomposition of daily trading volume within the Taiwan Stock Exchange Capitalization Weighted Stock Index (TWSE) into two subsets, comprising the trading volume of institutional investors and individual investors, we go on to investigate the influence of each subset on realized volatility. We reveal that the relatively rational sentiment of institutional investors plays a stabilizing role in future volatility, whereas the relatively irrational sentiment of individual investors tends to exacerbate such volatility. Therefore, we suggest that our modified model, which takes into account the relatively rational and irrational sentiment of investors, is capable of more accurately predicting volatility than the benchmark model.
Chemotherapy‐induced phlebitis via the GBP5/NLRP3 inflammasome axis and the therapeutic effect of aescin
Authors: Liu Peng , Ye Lichun , Ren Yongshen , Zhao Guodun , Zhang Yun , Lu Shaojuan , Li Qiang , Wu Chen , Bai Lijie , Zhang Zhongyun , Zhao Zhongqiu , Shi Zhaohua , Yin Shijin , Liao Maochuan , Lan Zhou , Feng Jing , Chen Lvyi 
Published: December 2022

Background and PurposeIntravenous infusion of chemotherapy drugs can cause severe chemotherapy‐induced phlebitis (CIP) in patients. However, the underlying mechanism of CIP development remains unclear.Experimental ApproachRNA‐sequencing analysis was used to identify potential disease targets in CIP. Guanylate binding protein‐5 (GBP5) genetic deletion approaches also were used to investigate the role of GBP5 in NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in lipopolysaccharide (LPS) primed murine bone‐marrow‐derived macrophages (BMDMs) induced by vinorelbine (VIN) in vitro and in mouse models of VIN‐induced CIP in vivo. The anti‐CIP effect of aescin was evaluated, both in vivo and in vivo.Key ResultsHere, we show that the expression of GBP5 was upregulated in human peripheral blood mononuclear cells from CIP patients. Genetic ablation of GBP5 in murine macrophages significantly alleviated VIN‐induced CIP in the experimental mouse model. Mechanistically, GBP5 contributed to the inflammatory responses through activating NLRP3 inflammasome and driving the production of the inflammatory cytokine IL‐1β. Moreover, aescin, a mixture of triterpene saponins extracted from horse chestnut seed, can alleviate CIP by inhibiting the GBP5/NLRP3 axis.Conclusion and ImplicationsThese findings suggest that GBP5 is an important regulator of NLRP3 inflammasome in CIP mouse model. Our work further reveals that aescin may serve as a promising candidate in the clinical treatment of CIP.
CD34dim cells identified as pluripotent stem cell‐derived definitive hemogenic endothelium purified using bone morphogenetic protein 4
Authors: Jeon Soo‐Been , Han A‐Reum , Lee Sunghun , Lee Seung Chan , Lee Min Ji , Park Soon‐Jung , Moon Sung‐Hwan , Lee Ji Yoon 
Published: December 2022

AbstractHemogenic endothelium (HE) plays a pivotal and inevitable role in haematopoiesis and can generate all blood and endothelial lineage cells in the aorta‐gonad‐mesonephros of mouse embryos. Whether definitive HE can prospectively isolate pure HE from human pluripotent stem cells that can spontaneously differentiate into heterogeneous cells remains unknown. Here, we identified and validated a CD34dim subpopulation with hemogenic potential. We also purified CD34 cells with a CXCR4−CD73− phenotype as a definitive HE population that generated haematopoietic stem cells and lymphocytes. The frequency of CXCR4−CD73−CD34dim was evidently increased by bone morphogenetic protein 4, and purified HE cells differentiated into haematopoietic cells with myeloid and T lymphoid lineages including Vδ2+ subset of γ/δ T cells. We developed a simple method to purify HE cells that were enriched in CD34dim cells. We uncovered an initial step in differentiating haematopoietic lineage cells that could be applied to basic and translational investigations into regenerative medicine.