bluuebunny/crossref_metadata_2025 huggingface dataset:
Terrorism in China and the Emerging Needs for Counter- Terrorism Medicine Following a Decade of Deaths and Injuries
Authors: Tin Derrick , Hart Alexander , Ciottone Gregory R.
Published: February 2021

Background:

China is ranked 42nd on the Global Terrorism Index (2019), a scoring system of terrorist activities. While China has a relatively low terrorism risk, events globally have wide-ranging repercussions for future attacks, putting first responders and emergency health workers at risk. This study aims to provide the epidemiological context for the past decade detailing the unique injury types responders are likely to encounter and to develop training programs utilizing these data.

Methods:

The Global Terrorism Database (GTD) was searched for all attacks in China between the years 2008-2018. Attacks met inclusion criteria if they fulfilled the terrorism-related criteria as set by the GTD’s Codebook. Ambiguous events, as defined by the GTD’s Codebook, were excluded. English language grey literature was searched to ensure no events meeting these criteria were missed. A focused search of online English language newspaper articles was also performed for any terrorist events between 2008-2018.

Results:

One-hundred and eight terrorist events occurred in the study time period. Of the 108 incidents, forty-seven (43.5%) involved Explosives/Bombs/Dynamite (E/B/D) only, with an average fatality count of 2.9 and injury count of 7.5 per event. Twenty-seven (25.0%) used bladed or blunt weapons in melees with an average fatality count of 9.7 and an injury count of 8.8 per event. Five (4.6%) involved incendiary weapons with an average fatality count of 2.4 and an injury count of 7.2 per event. Two used only chemical weapons (1.8%) with no recorded deaths and an injury count of 27.0 per event. Two events had unknown weapon types (1.8%) with one recorded death and no injury count. One event used a firearm (0.9%) and led to one death and no injuries. One event used a vehicle (0.9%), which also led to one death and no recorded injuries. Twenty-three attacks used a mix of weapons (21.2%) with an average fatality count of 17.1 and an injury count of 12.0 per event.

Conclusions:

One-hundred and eight terrorist attacks were recorded between 2008-2018 on Chinese soil using well-understood modalities. This resulted in a total of 809 recorded fatalities with 956 non-fatal injuries. The most commonly chosen methodology was E/B/D, followed by melees and the use of bladed weapons. Three events individually recorded a combined casualty toll of over 100 people.
The Ontological Work of Genre and Place:Wuthering Heightsand the Case of the Occulted Landscape
Authors: Goodlad Lauren M. E.
Published: February 2021

This essay shows howgenreandplaceenable the “ontological reading” of narrative fiction. Such sense-making dialectics enable readers to infer the terms of existence that shape fictional worlds. World-systems thinkers have theorized the critical premise of material worlds shaped though ongoing processes of combined and uneven development. Ontological reading is a comparative practice for studying the narrative work of “figuring out” those processes—for example, through the “occulted landscapes” of Yorkshire noir. Emily Brontë'sWuthering Heights() can be likened to a species of crime fiction in prefiguring the “hardboiled” pull from epistemological certainty to ontological complication. Whereas David Peace's millennialRed Ridingseries of novels and films palimpsestically layers multiple pasts and presents,Wuthering Heights’ photomontage-like landscape airbrushes the seams of combined and uneven histories. Both narratives evoke moorland terrains conducive to a long history of woolens manufacturing reliant on the energized capital and trade flows of Atlantic slavery. Both works body forth occulted landscapes with the capacity to narrate widely: their troubling of ontological difference—between human and animal, life and death, past and present, nature and supernature—lays the ground for generically flexile stories of regional becoming. Ontological reading thus widens literary study.
Socio-economic status and the double burden of malnutrition in Cambodia between 2000 and 2014: overweight mothers and stunted children
Authors: Nakphong Michelle K , Beltrán-Sánchez Hiram
Published: February 2021

Objective:

The Cambodian population has experienced an increase in the proportion of stunted children who have overweight mothers during a period of rapid social and economic growth. We aimed to identify socio-economic factors associated with this household-level double burden over time.

Design:

We used data from four Cambodia Demographic and Health Surveys from 2000 to 2014 to study the impact of socio-economic status (SES) on the link between child stunting and overweight mothers in two periods 2000–2005 v. 2010–2014. We hypothesised that SES would be a primary factor associated with this phenomenon.

Participants:

We included 14 988 children under the age of 5 years, among non-pregnant mothers aged 15–49 years of age and conducted analysis on a subsample of 1572 children with overweight mothers.

Setting:

Nationally representative household survey across all regions.

Results:

SES factors, specifically household wealth and maternal employment in service or manual occupations (in 2010–2014), are the main drivers of stunting among children of overweight mothers. Children with overweight mothers in the poorest households are more than twice as likely to be stunted than in the richest in both periods (2000–2005: adjusted OR (aOR) = 2·53, 95 % CI: 1·25, 5·13; 2010–2014: aOR = 2·61, 95 % CI: 1·43, 4·77), adjusting for other SES factors, indicating that despite decreasing income inequality, the poorest continue to bear excess risk of a double burden of malnutrition. Maternal short stature also doubled the likelihood of child stunting in both periods, which suggests intergenerational transmission of adversity and physical underdevelopment.

Conclusions:

Socio-economic inequalities should be addressed to reduce disparities in the household-level double burden of malnutrition.
‘Distant Reading’ in French Music Criticism
Authors: Joubert Estelle
Published: February 2021

This article offers a series of experiments exploring the potential for ‘distant reading’ in French music criticism. ‘Distant reading’, a term first coined by literary theorist Franco Moretti, refers to quantitative approaches that allow for new insights into a large corpus of texts by aggregating data. While the main corpus employed here is the Revue et gazette musicale de Paris (1831–1877), I also use secondary corpora of reviews of Félicien David's Herculanum in 1859, Berlioz's reviews of Gluck and Beethoven in the Journal des débats and reviews that mention Gabriel Fauré in the Library of Congress’ Chronicling America database. My experiments employ a text analysis tool named Voyant, built by Geoffrey Rockwell and Stéfan Sinclair, thereby also offering a basic introduction to the range of visualizations employed in distant reading. My experiments focus on areas in which quantitative methods are particularly well suited to generating new knowledge: corpus-wide visualizations and queries, moving beyond traditional text searching, investigations of music critics’ authorial styles and detecting sentiment in reviews, and finally, to geographies of music criticism.
Profiles of exposure to potentially traumatic events in refugees living in Australia
Authors: Nickerson A. , Byrow Y. , Rasmussen A. , O'Donnell M. , Bryant R. , Murphy S. , Mau V. , McMahon T. , Benson G. , Liddell B.
Published: February 2021

Aims

Refugees and asylum-seekers are typically exposed to multiple potentially traumatic events (PTEs) in the context of war, persecution and displacement, which confer elevated risk for psychopathology. There are significant limitations, however, in extant approaches to measuring these experiences in refugees. The current study aimed to identify profiles of PTE exposure, and the associations between these profiles and key demographics, contextual factors (including ongoing stressors, method of travel to Australia and separation from family), mental health and social outcomes, in a large sample of refugees resettled in Australia.

Methods

Participants were 1085 from Arabic, Farsi, Tamil and English-speaking refugee backgrounds who completed an online or pen-and-paper survey in their own language. Constructs measured included PTE exposure, demographics, pre-displacement factors, ongoing stressors, post-traumatic stress disorder symptoms, depression symptoms, anger reactions, plans of suicide and social engagement.

Results

Latent class analysis identified four profiles of PTE exposure, including the torture and pervasive trauma class, the violence exposure class, the deprivation exposure class and the low exposure class. Compared to the low exposure class, participants in the trauma-exposed classes were more likely to be male, highly educated, from Farsi and Tamil-speaking backgrounds, have travelled to Australia by boat, experience more ongoing stressors and report both greater psychological symptoms and social engagement.

Conclusions

This study found evidence for four distinct profiles of PTE exposure in a large sample of resettled refugees, and that these were associated with different demographic, psychological and social characteristics. These findings suggest that person-centred approaches represent an important potential avenue for investigation of PTE exposure in refugees, particularly with respect to identifying subgroups of refugees who may benefit from different types or levels of intervention according to their pre-migration PTE experiences.
Survey on weedy rice (Oryza spp.) management practice and adoption of Clearfield® rice technology in Peninsular Malaysia
Authors: Dilipkumar Masilamany , Ahmad-Hamdani Muhammad Saiful , Rahim Hairazi , Chuah Tse Seng , Burgos Nilda Roma
Published: February 2021

A total of 452 rice farmers from three main granary areas of Muda Agricultural Development Authority (MADA), Kemubu Agricultural Development Authority (KADA), and Integrated Agricultural Development Area Barat Laut Selangor (IADA BLS) were surveyed in 2019. The goal was to determine farmers’ knowledge of and management practices for weedy rice (Oryza spp.) as well as the adoption level of Clearfield® rice technology (CRT) in Malaysia. Most farmers (74%) were adept at recognizing weedy rice. The majority of farmers (77%) perceived transplanting and water seeding rice systems as the best options to manage weedy rice, while only 10% of the farmers adopted CRT. The low level of adoption of this technology was due to several constraints, including the high cost of the CRT package and occurrence of imidazolinone (IMI)-resistant weedy rice in their farms. Farmers from MADA and IADA BLS reported the occurrence of IMI weedy rice in their farms for more than nine planting seasons, whereas those from KADA reported having resistant weedy rice for five to six planting seasons. The main factor contributing to the evolution of IMI-resistant weedy rice was ignorance about the technology and deliberate disregard of stewardship guidelines. The survey revealed that there is a need to increase awareness about CRT through training and educational programs for proper adoption of this technology.
Carbonaceous Aerosol Characterization and Their Relationship With Meteorological Parameters During Summer Monsoon and Winter Monsoon at an Industrial Region in Delhi, India
Authors: Sonwani Saurabh , Saxena Pallavi , Shukla Anuradha
Published: February 2021

PM10 samples were collected and atmospheric organic carbon (OC) and elemental carbon (EC) were determined during summer monsoon (SM) and winter monsoon (WM) seasons in 2016–2017 at an industrial location in New Delhi, India. Owing to high combustion and emission activities in the industrial area, it was imperative to characterize the carbonaceous aerosols, including their morphology and seasonal distribution. The mean PM10 concentration was 144 ± 53.7 and 210.4 ± 50.7 μg/m3 in SM and WM, respectively, with an overall average of 174.6 ± 64 μg/m3. Moreover, the OC concentration was 70.3 ± 53.7 and 94.3 ± 40.3 μgC/m3 during the SM and WM, respectively, with an overall average of 79.9 ± 44.9 μgC/m3, and the EC concentration was 50.8 ± 53 and 62.6 ± 49.8 μgC/m3, respectively, with an overall average of 58.3 ± 46.7 μgC/m3. The morphological observations of collected particles were studied and the char/soot particles, iron‐rich particles, and aggregates of calcium sulfate particles were observed during both the seasons. However, the predominance of combustion‐derived particles such as soot and char was higher in the WM than in the SM. Further, the OC/EC ratio suggested the presence of mixed sources at the industrial location, predominated by industry and motor vehicle emissions. The relationship of carbonaceous aerosol with meteorological variables was also studied, and it was found that temperature, atmospheric stability, wind direction, and rain intensity significantly affect the levels of OC as compared to that of EC during both seasons.
Thermo‐Hydro‐Mechanical Model and Caprock Deformation Explain the Onset of an Ongoing Seismo‐Volcanic Unrest
Authors: Akande Waheed Gbenga , Gan Quan , Cornwell David G. , De Siena Luca
Published: February 2021

Modeling seismicity at volcanoes remains challenging as the processes that control seismic energy release due to fluid transport, heat flow, and rock deformation are firmly coupled in complex geological media. Here, we couple fluid‐flow and mechanical (deformation) simulators (TOUGHREACT–FLAC3D) to reproduce fluid‐induced seismicity at Campi Flegrei caldera (southern Italy) in isothermal (HM) and nonisothermal (THM) conditions. The unique ability of the Campi Flegrei caprock to withstand stress induced by hot‐water injections is included in the model parametrization. After pore pressure accumulation is guided by a combination of thermal and hydromechanical interactions, contrasting compressive and extensional forces act on the basal and top parts of the caprock, respectively. Then, pressure perturbation and caprock deformation induce fractures that allow hot fluids uprising to pressurize the overlying fault, driving it toward failure and triggering seismicity. Under similar mechanical boundary conditions, the induced thermal effects prompt seismic slip earlier but with higher seismic magnitudes when (1) thermal equilibrium is preserved and (2) the thermal contrast is enhanced due to increased fluid injection temperatures. The results indicate that numerical models of volcano seismicity must consider the influence of rock‐sealing formations to obtain more robust, accurate, and realistic seismic predictions at volcanoes. The proposed models satisfactorily reproduce the magnitude–depth distribution of the swarm (October 5, 2019), preceding the two strongest earthquakes recorded in 35 years at the caldera (3.1 and 3.3—on December 6, 2019, and April 26, 2020, respectively) using hot‐water injection from depth.
Controlling Factors of Methane in Tropical Lakes of Different Depths
Authors: Mendoza‐Pascual Milette U. , Itoh Masayuki , Aguilar Jaydan I. , Padilla Karol Sophia Agape R. , Papa Rey Donne S. , Okuda Noboru
Published: February 2021

To understand methane (CH4) dynamics in tropical lakes and describe their importance in overall CH4 emissions, we observed temporal trends of CH4 stored in the water columns of Philippine lakes of different depths (shallow, moderately deep, and deep). We detected higher CH4 stored in profundal anoxic layers of deeper lakes. The average surface and profundal CH4 concentrations throughout our monthly monitoring were 0.27 ± 0.07 and 421 ± 189 μmol L–1 in the shallow lake, 0.48 ± 0.37 and 1,121 ± 125 μmol L–1 in the moderately deep lake, and 0.34 ± 0.23 and 943 ± 119 μmol L–1 in the deep lake. The fate of CH4 stored in the water column was related to depth, owing to different stratification and mixing regimes. Analyses of temporal relationships of CH4 with daily weather and physicochemical parameters revealed their impact on CH4 dynamics by controlling the frequency and mixing intensity throughout the year. Only shallow lake exhibited increase in CH4 concentrations with lowering atmospheric pressure. This allows vertical mixing and transport of CH4 from deeper to shallower layers. In moderately deep, and deep lakes, effects of daily weather parameters were not apparent on CH4 concentrations in the deepest layers (below 30 m depth). This suggests that lake depth and stratification should be considered for precise estimation of tropical lakes' CH4 emissions. Comparison with lakes under different climate conditions revealed the importance of tropical lakes for surface CH4 emission due to higher surface CH4 concentrations. Changes in water temperature is one of the factors controlling profundal CH4 production, storage, and its transport to shallower layer.
Physically Based Scaling Models to Predict Gas Transfer Velocity in Streams and Rivers
Authors: Wang Junna , Bombardelli Fabián A. , Dong Xiaoli
Published: February 2021

Air‐water gas transfer influences fundamental processes of aquatic systems such as photosynthesis, respiration, and greenhouse gas emission. Previous predictive models for gas transfer velocity (KL) often only apply to a small range of streams and rivers. Two “universal” scalings, KL ∼ 1/4 power of turbulent dissipation rate (ε1/4) and KL ∼ shear velocity (U*), deduced from classic thin‐film theory and surface renewal theory, have been reported for lake and marine systems, but have not been adequately tested for streams or rivers. To test the two scalings and understand how KL varies across systems, we compiled 588 field measurements of KL, and used inverse modeling based on long‐term high‐frequency dissolved oxygen time series to estimate KL of 35 streams and rivers capturing a wide range of discharge (0–221 m3/s). We found that the two scalings held for both the KL estimated by inverse modeling and the KL from measurements and outperformed 23 previous models in predicting KL. Furthermore, the main driver of KL variation shifts from bottom friction to other factors with increasing stream/river size. In most streams and a few rivers, correlation between U* and KL is high, and discharge‐KL relationships are strongly positive, indicating that turbulence generated by bottom friction dominates near‐surface turbulence, a fundamental control of KL, thus, the two scaling models are applicable to these systems. However, most rivers (mean discharge >10 m3/s) show low correlations between U* and KL, suggesting biochemical factors and winds likely override bottom friction in driving near‐surface turbulence and KL.
High glucose induces Drp1-mediated mitochondrial fission via the Orai1 calcium channel to participate in diabetic cardiomyocyte hypertrophy
Authors: Wu Qing-Rui , Zheng Dan-Lin , Liu Pei-Ming , Yang Hui , Li Lu-An , Kuang Su-Juan , Lai Ying-Yu , Rao Fang , Xue Yu-Mei , Lin Ji-Jin , Liu Shuang-Xin , Chen Chun-Bo , Deng Chun-Yu
Published: February 2021

Mitochondrial dysfunction and impaired Ca2+ handling are involved in the development of diabetic cardiomyopathy (DCM). Dynamic relative protein 1 (Drp1) regulates mitochondrial fission by changing its level of phosphorylation, and the Orai1 (Ca2+ release-activated calcium channel protein 1) calcium channel is important for the increase in Ca2+ entry into cardiomyocytes. We aimed to explore the mechanism of Drp1 and Orai1 in cardiomyocyte hypertrophy caused by high glucose (HG). We found that Zucker diabetic fat rats induced by administration of a high-fat diet develop cardiac hypertrophy and impaired cardiac function, accompanied by the activation of mitochondrial dynamics and calcium handling pathway-related proteins. Moreover, HG induces cardiomyocyte hypertrophy, accompanied by abnormal mitochondrial morphology and function, and increased Orai1-mediated Ca2+ influx. Mechanistically, the Drp1 inhibitor mitochondrial division inhibitor 1 (Mdivi-1) prevents cardiomyocyte hypertrophy induced by HG by reducing phosphorylation of Drp1 at serine 616 (S616) and increasing phosphorylation at S637. Inhibition of Orai1 with single guide RNA (sgOrai1) or an inhibitor (BTP2) not only suppressed Drp1 activity and calmodulin-binding catalytic subunit A (CnA) and phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) expression but also alleviated mitochondrial dysfunction and cardiomyocyte hypertrophy caused by HG. In addition, the CnA inhibitor cyclosporin A and p-ERK1/2 inhibitor U0126 improved HG-induced cardiomyocyte hypertrophy by promoting and inhibiting phosphorylation of Drp1 at S637 and S616, respectively. In summary, we identified Drp1 as a downstream target of Orai1-mediated Ca2+ entry, via activation by p-ERK1/2-mediated phosphorylation at S616 or CnA-mediated dephosphorylation at S637 in DCM. Thus, the Orai1–Drp1 axis is a novel target for treating DCM.
AAV-mediated inhibition of ULK1 promotes axonal regeneration in the central nervous system in vitro and in vivo
Authors: Ribas Vinicius Toledo , Vahsen Björn Friedhelm , Tatenhorst Lars , Estrada Veronica , Dambeck Vivian , Almeida Raquel Alves , Bähr Mathias , Michel Uwe , Koch Jan Christoph , Müller Hans Werner , Lingor Paul
Published: February 2021

Axonal damage is an early step in traumatic and neurodegenerative disorders of the central nervous system (CNS). Damaged axons are not able to regenerate sufficiently in the adult mammalian CNS, leading to permanent neurological deficits. Recently, we showed that inhibition of the autophagic protein ULK1 promotes neuroprotection in different models of neurodegeneration. Moreover, we demonstrated previously that axonal protection improves regeneration of lesioned axons. However, whether axonal protection mediated by ULK1 inhibition could also improve axonal regeneration is unknown. Here, we used an adeno-associated viral (AAV) vector to express a dominant-negative form of ULK1 (AAV.ULK1.DN) and investigated its effects on axonal regeneration in the CNS. We show that AAV.ULK1.DN fosters axonal regeneration and enhances neurite outgrowth in vitro. In addition, AAV.ULK1.DN increases neuronal survival and enhances axonal regeneration after optic nerve lesion, and promotes long-term axonal protection after spinal cord injury (SCI) in vivo. Interestingly, AAV.ULK1.DN also increases serotonergic and dopaminergic axon sprouting after SCI. Mechanistically, AAV.ULK1.DN leads to increased ERK1 activation and reduced expression of RhoA and ROCK2. Our findings outline ULK1 as a key regulator of axonal degeneration and regeneration, and define ULK1 as a promising target to promote neuroprotection and regeneration in the CNS.
SIRT1 attenuates sepsis-induced acute kidney injury via Beclin1 deacetylation-mediated autophagy activation
Authors: Deng Zhiya , Sun Maomao , Wu Jie , Fang Haihong , Cai Shumin , An Sheng , Huang Qiaobing , Chen Zhenfeng , Wu Chenglun , Zhou Ziwei , Hu Haoran , Zeng Zhenhua
Published: February 2021

Our previous studies showed that silent mating-type information regulation 2 homologue-1 (SIRT1, a deacetylase) upregulation could attenuate sepsis-induced acute kidney injury (SAKI). Upregulated SIRT1 can deacetylate certain autophagy-related proteins (Beclin1, Atg5, Atg7 and LC3) in vitro. However, it remains unclear whether the beneficial effect of SIRT1 is related to autophagy induction and the underlying mechanism of this effect is also unknown. In the present study, caecal ligation and puncture (CLP)-induced mice, and an LPS-challenged HK-2 cell line were established to mimic a SAKI animal model and a SAKI cell model, respectively. Our results demonstrated that SIRT1 activation promoted autophagy and attenuated SAKI. SIRT1 deacetylated only Beclin1 but not the other autophagy-related proteins in SAKI. SIRT1-induced autophagy and its protective effect against SAKI were mediated by the deacetylation of Beclin1 at K430 and K437. Moreover, two SIRT1 activators, resveratrol and polydatin, attenuated SAKI in CLP-induced septic mice. Our study was the first to demonstrate the important role of SIRT1-induced Beclin1 deacetylation in autophagy and its protective effect against SAKI. These findings suggest that pharmacologic induction of autophagy via SIRT1-mediated Beclin1 deacetylation may be a promising therapeutic approach for future SAKI treatment.
Sunitinib treatment promotes metastasis of drug-resistant renal cell carcinoma via TFE3 signaling pathway
Authors: Li Luchao , Zhao Shuo , Liu Zhengfang , Zhang Nianzhao , Pang Shuo , Liu Jikai , Liu Cheng , Fan Yidong
Published: February 2021

Receptor tyrosine kinase (RTK) inhibitors, such as sunitinib and sorafenib, remain the first-line drugs for the treatment of mRCC. Acquired drug resistance and metastasis are the main causes of treatment failure. However, in the case of metastasis Renal Cell Cancer (mRCC), which showed a good response to sunitinib, we found that long-term treatment with sunitinib could promote lysosome biosynthesis and exocytosis, thereby triggering the metastasis of RCC. By constructing sunitinib-resistant cell lines in vivo, we confirmed that TFE3 plays a key role in the acquired resistance to sunitinib in RCC. Under the stimulation of sunitinib, TFE3 continued to enter the nucleus, promoting the expression of endoplasmic reticulum (ER) protein E-Syt1. E-Syt1 and the lysosomal membrane protein Syt7 form a heterodimer, which induces ER fragmentation, Ca2+ release, and lysosomal exocytosis. Lysosomal exocytosis has two functions: pumping sunitinib out from the cytoplasm, which promotes resistance to sunitinib in RCC, releasing cathepsin B (CTSB) into the extracellular matrix (ECM), which can degrade the ECM to enhance the invasion and metastasis ability of RCC. Our study found that although sunitinib is an effective drug for the treatment of mRCC, once RCC has acquired resistance to sunitinib, sunitinib treatment will promote metastasis.
Obesity-associated up-regulation of lipocalin 2 protects gastric mucosa cells from apoptotic cell death by reducing endoplasmic reticulum stress
Authors: Wen Xin , Su Bin , Gao Mingming , Chen Jiaqi , Zhou Donglei , You Hui , Li Nannan , Chang Shuaikang , Cheng Xiaoyun , Qian Chunhua , Gao Jingyang , Yang Peng , Qu Shen , Bu Le
Published: February 2021

Gastric mucosal injury is a less well known complication of obesity. Its mechanism remains to be further elucidated. Here, we explored the protective role of lipocalin 2 (LCN2) against endoplasmic reticulum stress and cell apoptosis in gastric mucosa in patients and mice with obesity. Through molecular and genetic analyses in clinical species, LCN2 secreted by parietal cells expression is elevated in obese. Immunofluorescence, TUNEL, and colorimetry results show that a more significant upregulation of pro-inflammatory factors and increased amount of apoptotic cells in gastric tissue sections in obese groups. Loss- and gain-of-function experiments in gastric epithelial cells demonstrate that increased LCN2 protected against obesity associated gastric injury by inhibiting apoptosis and improving inflammatory state. In addition, this protective effect was mediated by repressing ER stress. Our findings identify LCN2 as a gastric hormone could be a compensatory protective factor against gastric injury in obese.
Regulation of MYB by distal enhancer elements in human myeloid leukemia
Authors: Li Mengjia , Jiang Penglei , Cheng Kai , Zhang Zehui , Lan Shuyu , Li Xiaoxia , Zhao Lirong , Wang Yucheng , Wang Xiang , Chen Jing , Ji Tao , Han Bingshe , Zhang Junfang
Published: February 2021

MYB plays vital roles in regulating proliferation and differentiation of hematopoietic progenitor cells, dysregulation of MYB has been implicated in the pathogenesis of leukemia. Although the transcription of MYB has been well studied, its detailed underlying regulatory mechanisms still remain elusive. Here, we detected the long-range interaction between the upstream regions, −34k and −88k, and the MYB promoter in K562, U937, and HL-60 cells using circularized chromosome conformation capture (4C) assay, which declined when MYB was downregulated during chemical-induced differentiation. The enrichment of enhancer markers, H3K4me1 and H3K27ac, and enhancer activity at the −34k and −88k regions were confirmed by ChIP-qPCR and luciferase assay respectively. ChIP-qPCR showed the dynamic binding of GATA1, TAL1, and CCAAT/enhancer-binding protein (C/EBPβ) at −34k and −88k during differentiation of K562 cells. Epigenome editing by a CRISPR-Cas9-based method showed that H3K27ac at −34k enhanced TF binding and MYB expression, while DNA methylation inhibited MYB expression. Taken together, our data revealed that enhancer elements at −34k are required for MYB expression, TF binding, and epigenetic modification are closely involved in this process in human myeloid leukemia cells.
Transcriptional network constituted of CBP, Ku70, NOX2, and BAX prevents the cell death of necrosis, paraptosis, and apoptosis in human melanoma
Authors: Ding Liang , Wen Yalei , Zhang Xin , Zhao Fang , Lv Kenao , Shi Jian-hong , Shen Shigang , Pan Xuefeng
Published: February 2021

CREB-binding protein (CBP) is an acetyltransferase known to play multiple roles in the transcriptions of genes involving oxidative metabolism, cell cycle, DNA damage checkpoints, and cell death. In this study, CBP was found to positively regulate the expression of Ku70, and both CBP and Ku70 were found to negatively regulate the expression of NOX2, therefore, mitigating the intracellular ROS in human melanoma. Knocking down CBP or Ku70 induced necrotic and paraptotic cell death as indicated by high-level intracellular ROS, cytoplasmic vacuolization, and cell cycle arrest in the S phase. In addition, chromosomal condensations were also observed in the cells proceeding necrotic and paraptotic cell death, which was found to be related to the BAX-associated intrinsic pathway of apoptotic cell death, when Ku70 was decreased either by CBP depletion or by Ku70 depletion directly. Our results, therefore, supported the idea that CBP, Ku70, BAX, and NOX2 have formed a transcriptional network in the prevention of cell death of necrosis, paraptosis, and apoptosis in human melanoma.
Cholesterol activates the Wnt/PCP-YAP signaling in SOAT1-targeted treatment of colon cancer
Authors: Xu Huanji , Xia Hongwei , Zhou Sheng , Tang Qiulin , Bi Feng
Published: February 2021

Intracellular free cholesterol can be converted to cholesteryl ester and stored as lipid droplets through SOAT1-mediated esterification. Compelling evidence implicate targeting SOAT1 as a promising therapeutic strategy for cancer management. Herein, we demonstrate how targeting SOAT1 promotes YAP expression by elevating cellular cholesterol content in colon cancer cells. Results revealed that cholesterol alleviates the inhibitory effect of LRP6 on the Wnt/PCP pathway by impeding the interaction of LRP6 with FZD7. Subsequently, FZD7-mediated PCP signaling directly elevated YAP expression by activating RhoA. Nystatin-mediated cholesterol sequestration significantly inhibited YAP expression under SOAT1 inhibition. Moreover, nystatin synergized with the SOAT1 inhibitor avasimibe in suppressing the viability of colon cancer cells in vitro and in vivo. The present study provides new mechanistic insights into the functions of cholesterol metabolism on growth signaling pathways and implicates a novel strategy for cholesterol metabolic-targeted treatment of colon cancers.
Organic magnetoelectric and optomagnetic couplings: perspectives for organic spin optoelectronics
Authors: Wang Zhongxuan , Qin Wei
Published: February 2021

Over the past years, the development of organic ferromagnetic materials has been investigated worldwide for potential applications. Due to the couplings among the charge, orbit, spin, and phonon in organic ferromagnetic materials, magnetoelectric, and optomagnetic couplings have been realized and observed. In this review, progress in organic magnetoelectric and optomagnetic couplings is presented, and the mechanisms behind the phenomena are also briefly summarized. Hopefully, the understanding of magnetoelectric and optomagnetic couplings could provide guidance for the further development of organic spin optoelectronics.
PlasmidHawk improves lab of origin prediction of engineered plasmids using sequence alignment
Authors: Wang Qi , Kille Bryce , Liu Tian Rui , Elworth R. A. Leo , Treangen Todd J.
Published: February 2021

With advances in synthetic biology and genome engineering comes a heightened awareness of potential misuse related to biosafety concerns. A recent study employed machine learning to identify the lab-of-origin of DNA sequences to help mitigate some of these concerns. Despite their promising results, this deep learning based approach had limited accuracy, was computationally expensive to train, and wasn’t able to provide the precise features that were used in its predictions. To address these shortcomings, we developed PlasmidHawk for lab-of-origin prediction. Compared to a machine learning approach, PlasmidHawk has higher prediction accuracy; PlasmidHawk can successfully predict unknown sequences’ depositing labs 76% of the time and 85% of the time the correct lab is in the top 10 candidates. In addition, PlasmidHawk can precisely single out the signature sub-sequences that are responsible for the lab-of-origin detection. In summary, PlasmidHawk represents an explainable and accurate tool for lab-of-origin prediction of synthetic plasmid sequences. PlasmidHawk is available at https://gitlab.com/treangenlab/plasmidhawk.git.
Mechanically robust amino acid crystals as fiber-optic transducers and wide bandpass filters for optical communication in the near-infrared
Authors: Karothu Durga Prasad , Dushaq Ghada , Ahmed Ejaz , Catalano Luca , Polavaram Srujana , Ferreira Rodrigo , Li Liang , Mohamed Sharmarke , Rasras Mahmoud , Naumov Panče
Published: February 2021

Organic crystals are emerging as mechanically compliant, light-weight and chemically versatile alternatives to the commonly used silica and polymer waveguides. However, the previously reported organic crystals were shown to be able to transmit visible light, whereas actual implementation in telecommunication devices requires transparency in the near-infrared spectral range. Here we demonstrate that single crystals of the amino acid L-threonine could be used as optical waveguides and filters with high mechanical and thermal robustness for transduction of signals in the telecommunications range. On their (00$$\bar 1$$

1

¯

) face, crystals of this material have an extraordinarily high Young’s modulus (40.95 ± 1.03 GPa) and hardness (1.98 ± 0.11 GPa) for an organic crystal. First-principles density functional theory calculations, used in conjunction with analysis of the energy frameworks to correlate the structure with the anisotropy in the Young’s modulus, showed that the high stiffness arises as a consequence of the strong charge-assisted hydrogen bonds between the zwitterions. The crystals have low optical loss in the O, E, S and C bands of the spectrum (1250−1600 nm), while they effectively block infrared light below 1200 nm. This property favors these and possibly other related organic crystals as all-organic fiber-optic waveguides and filters for transduction of information.
Direct imaging and electronic structure modulation of moiré superlattices at the 2D/3D interface
Authors: Reidy Kate , Varnavides Georgios , Thomsen Joachim Dahl , Kumar Abinash , Pham Thang , Blackburn Arthur M. , Anikeeva Polina , Narang Prineha , LeBeau James M. , Ross Frances M.
Published: February 2021

The atomic structure at the interface between two-dimensional (2D) and three-dimensional (3D) materials influences properties such as contact resistance, photo-response, and high-frequency electrical performance. Moiré engineering is yet to be utilized for tailoring this 2D/3D interface, despite its success in enabling correlated physics at 2D/2D interfaces. Using epitaxially aligned MoS2/Au{111} as a model system, we demonstrate the use of advanced scanning transmission electron microscopy (STEM) combined with a geometric convolution technique in imaging the crystallographic 32 Å moiré pattern at the 2D/3D interface. This moiré period is often hidden in conventional electron microscopy, where the Au structure is seen in projection. We show, via ab initio electronic structure calculations, that charge density is modulated according to the moiré period, illustrating the potential for (opto-)electronic moiré engineering at the 2D/3D interface. Our work presents a general pathway to directly image periodic modulation at interfaces using this combination of emerging microscopy techniques.
Picosecond time-resolved photon antibunching measures nanoscale exciton motion and the true number of chromophores
Authors: Hedley Gordon J. , Schröder Tim , Steiner Florian , Eder Theresa , Hofmann Felix J. , Bange Sebastian , Laux Dirk , Höger Sigurd , Tinnefeld Philip , Lupton John M. , Vogelsang Jan
Published: February 2021

The particle-like nature of light becomes evident in the photon statistics of fluorescence from single quantum systems as photon antibunching. In multichromophoric systems, exciton diffusion and subsequent annihilation occurs. These processes also yield photon antibunching but cannot be interpreted reliably. Here we develop picosecond time-resolved antibunching to identify and decode such processes. We use this method to measure the true number of chromophores on well-defined multichromophoric DNA-origami structures, and precisely determine the distance-dependent rates of annihilation between excitons. Further, this allows us to measure exciton diffusion in mesoscopic H- and J-type conjugated-polymer aggregates. We distinguish between one-dimensional intra-chain and three-dimensional inter-chain exciton diffusion at different times after excitation and determine the disorder-dependent diffusion lengths. Our method provides a powerful lens through which excitons can be studied at the single-particle level, enabling the rational design of improved excitonic probes such as ultra-bright fluorescent nanoparticles and materials for optoelectronic devices.
Machine learning in spectral domain
Authors: Giambagli Lorenzo , Buffoni Lorenzo , Carletti Timoteo , Nocentini Walter , Fanelli Duccio
Published: February 2021

Deep neural networks are usually trained in the space of the nodes, by adjusting the weights of existing links via suitable optimization protocols. We here propose a radically new approach which anchors the learning process to reciprocal space. Specifically, the training acts on the spectral domain and seeks to modify the eigenvalues and eigenvectors of transfer operators in direct space. The proposed method is ductile and can be tailored to return either linear or non-linear classifiers. Adjusting the eigenvalues, when freezing the eigenvectors entries, yields performances that are superior to those attained with standard methods restricted to operate with an identical number of free parameters. To recover a feed-forward architecture in direct space, we have postulated a nested indentation of the eigenvectors. Different non-orthogonal basis could be employed to export the spectral learning to other frameworks, as e.g. reservoir computing.
Marine furanocembranoids-inspired macrocycles enabled by Pd-catalyzed unactivated C(sp3)-H olefination mediated by donor/donor carbenes
Authors: Hao Jiping , Guo Xueying , He Shijun , Xu Zhongliang , Chen Lu , Li Zhongyu , Song Bichao , Zuo Jianping , Lin Zhenyang , Yang Weibo
Published: February 2021

Biomimetic modularization and function-oriented synthesis of structurally diversified natural product-like macrocycles in a step-economical fashion is highly desirable. Inspired by marine furanocembranoids, herein, we synthesize diverse alkenes substituted furan-embedded macrolactams via a modular biomimetic assembly strategy. The success of this assembly is the development of crucial Pd-catalyzed carbene coupling between ene-yne-ketones as donor/donor carbene precursors and unactivated Csp3‒H bonds which represents a great challenge in organic synthesis. Notably, this method not only obviates the use of unstable, explosive, and toxic diazo compounds, but also can be amenable to allenyl ketones carbene precursors. DFT calculations demonstrate that a formal 1,4-Pd shift could be involved in the mechanism. Moreover, the collected furanocembranoids-like macrolactams show significant anti-inflammatory activities against TNF-α, IL-6, and IL-1β and the cytotoxicity is comparable to Dexamethasone.
Mechanochemical control of epidermal stem cell divisions by B-plexins
Authors: Jiang Chen , Javed Ahsan , Kaiser Laura , Nava Michele M. , Xu Rui , Brandt Dominique T. , Zhao Dandan , Mayer Benjamin , Fernández-Baldovinos Javier , Zhou Luping , Höß Carsten , Sawmynaden Kovilen , Oleksy Arkadiusz , Matthews David , Weinstein Lee S. , Hahn Heidi , Gröne Hermann-Josef , Graumann Peter L. , Niessen Carien M. , Offermanns Stefan , Wickström Sara A. , Worzfeld Thomas
Published: February 2021

The precise spatiotemporal control of cell proliferation is key to the morphogenesis of epithelial tissues. Epithelial cell divisions lead to tissue crowding and local changes in force distribution, which in turn suppress the rate of cell divisions. However, the molecular mechanisms underlying this mechanical feedback are largely unclear. Here, we identify a critical requirement of B-plexin transmembrane receptors in the response to crowding-induced mechanical forces during embryonic skin development. Epidermal stem cells lacking B-plexins fail to sense mechanical compression, resulting in disinhibition of the transcriptional coactivator YAP, hyperproliferation, and tissue overgrowth. Mechanistically, we show that B-plexins mediate mechanoresponses to crowding through stabilization of adhesive cell junctions and lowering of cortical stiffness. Finally, we provide evidence that the B-plexin-dependent mechanochemical feedback is also pathophysiologically relevant to limit tumor growth in basal cell carcinoma, the most common type of skin cancer. Our data define a central role of B-plexins in mechanosensation to couple cell density and cell division in development and disease.
A CSB-PAF1C axis restores processive transcription elongation after DNA damage repair
Authors: van den Heuvel Diana , Spruijt Cornelia G. , González-Prieto Román , Kragten Angela , Paulsen Michelle T. , Zhou Di , Wu Haoyu , Apelt Katja , van der Weegen Yana , Yang Kevin , Dijk Madelon , Daxinger Lucia , Marteijn Jurgen A. , Vertegaal Alfred C. O. , Ljungman Mats , Vermeulen Michiel , Luijsterburg Martijn S.
Published: February 2021

Bulky DNA lesions in transcribed strands block RNA polymerase II (RNAPII) elongation and induce a genome-wide transcriptional arrest. The transcription-coupled repair (TCR) pathway efficiently removes transcription-blocking DNA lesions, but how transcription is restored in the genome following DNA repair remains unresolved. Here, we find that the TCR-specific CSB protein loads the PAF1 complex (PAF1C) onto RNAPII in promoter-proximal regions in response to DNA damage. Although dispensable for TCR-mediated repair, PAF1C is essential for transcription recovery after UV irradiation. We find that PAF1C promotes RNAPII pause release in promoter-proximal regions and subsequently acts as a processivity factor that stimulates transcription elongation throughout genes. Our findings expose the molecular basis for a non-canonical PAF1C-dependent pathway that restores transcription throughout the human genome after genotoxic stress.
Quasi-one-dimensional metallic conduction channels in exotic ferroelectric topological defects
Authors: Yang Wenda , Tian Guo , Zhang Yang , Xue Fei , Zheng Dongfeng , Zhang Luyong , Wang Yadong , Chen Chao , Fan Zhen , Hou Zhipeng , Chen Deyang , Gao Jinwei , Zeng Min , Qin Minghui , Chen Long-Qing , Gao Xingsen , Liu Jun-Ming
Published: February 2021

Ferroelectric topological objects provide a fertile ground for exploring emerging physical properties that could potentially be utilized in future nanoelectronic devices. Here, we demonstrate quasi-one-dimensional metallic high conduction channels associated with the topological cores of quadrant vortex domain and center domain (monopole-like) states confined in high quality BiFeO3 nanoislands, abbreviated as the vortex core and the center core. We unveil via the phase-field simulation that the superfine metallic conduction channels along the center cores arise from the screening charge carriers confined at the core region, whereas the high conductance of vortex cores results from a field-induced twisted state. These conducting channels can be reversibly created and deleted by manipulating the two topological states via electric field, leading to an apparent electroresistance effect with an on/off ratio higher than 103. These results open up the possibility of utilizing these functional one-dimensional topological objects in high-density nanoelectronic devices, e.g. nonvolatile memory.
Pre-mitotic genome re-organisation bookends the B cell differentiation process
Authors: Chan Wing Fuk , Coughlan Hannah D. , Zhou Jie H. S. , Keenan Christine R. , Bediaga Naiara G. , Hodgkin Philip D. , Smyth Gordon K. , Johanson Timothy M. , Allan Rhys S.
Published: February 2021

During cellular differentiation chromosome conformation is intricately remodelled to support the lineage-specific transcriptional programs required for initiating and maintaining lineage identity. When these changes occur in relation to cell cycle, division and time in response to cellular activation and differentiation signals has yet to be explored, although it has been proposed to occur during DNA synthesis or after mitosis. Here, we elucidate the chromosome conformational changes in B lymphocytes as they differentiate and expand from a naive, quiescent state into antibody secreting plasma cells. We find gene-regulatory chromosome reorganization in late G1 phase before the first division, and that this configuration is remarkably stable as the cells massively and rapidly clonally expand. A second wave of conformational change occurs as cells terminally differentiate into plasma cells, coincident with increased time in G1 phase. These results provide further explanation for how lymphocyte fate is imprinted prior to the first division. They also suggest that chromosome reconfiguration occurs prior to DNA replication and mitosis, and is linked to a gene expression program that controls the differentiation process required for the generation of immunity.
System-wide identification and prioritization of enzyme substrates by thermal analysis
Authors: Saei Amir Ata , Beusch Christian M. , Sabatier Pierre , Wells Juan Astorga , Gharibi Hassan , Meng Zhaowei , Chernobrovkin Alexey , Rodin Sergey , Näreoja Katja , Thorsell Ann-Gerd , Karlberg Tobias , Cheng Qing , Lundström Susanna L. , Gaetani Massimiliano , Végvári Ákos , Arnér Elias S. J. , Schüler Herwig , Zubarev Roman A.
Published: February 2021

Despite the immense importance of enzyme–substrate reactions, there is a lack of general and unbiased tools for identifying and prioritizing substrate proteins that are modified by the enzyme on the structural level. Here we describe a high-throughput unbiased proteomics method called System-wide Identification and prioritization of Enzyme Substrates by Thermal Analysis (SIESTA). The approach assumes that the enzymatic post-translational modification of substrate proteins is likely to change their thermal stability. In our proof-of-concept studies, SIESTA successfully identifies several known and novel substrate candidates for selenoprotein thioredoxin reductase 1, protein kinase B (AKT1) and poly-(ADP-ribose) polymerase-10 systems. Wider application of SIESTA can enhance our understanding of the role of enzymes in homeostasis and disease, opening opportunities to investigate the effect of post-translational modifications on signal transduction and facilitate drug discovery.