bluuebunny/crossref_metadata_2025 huggingface dataset:
Venture creation patterns in academic entrepreneurship: the role of founder motivations
Authors: Hossinger Stefan , Block Jörn , Chen Xiangyu , Werner Arndt
Published: November 2021

The path to academic entrepreneurship is characterized by a sequence of venture creation activities, which can be classified into operational-, financing- and commercialization activities. Academic entrepreneurship research is concerned with the question how different motives of scientists affect the patterns of these venture creation activities. Using a longitudinal two-period dataset of 165 academic entrepreneurs from 73 universities in Germany, we propose and test a multi-activity-based model that links different types of entrepreneurial motives to venture creation activities. The findings show that founder motives related to self-realization, necessity and an increased financial income increase the likelihood of completing venture creation activities, whereas work-life balance motivations and the drive to make better use of one’s professional knowledge decrease that likelihood. The desire to translate research ideas into practice has no effect. Our results further show that the positive effects of seeking self-realization and an increased financial income are more pronounced for completing commercialization activities than for operational activities. Our study contributes to research on academic entrepreneurship and entrepreneurial motivations and helps university administrators and policymakers to design their entrepreneurship support programs more effectively.
The energetic barrier to single-file water flow through narrow channels
Authors: Pfeffermann Juergen , Goessweiner-Mohr Nikolaus , Pohl Peter
Published: November 2021

Various nanoscopic channels of roughly equal diameter and length facilitate single-file diffusion at vastly different rates. The underlying variance of the energetic barriers to transport is poorly understood. First, water partitioning into channels so narrow that individual molecules cannot overtake each other incurs an energetic penalty. Corresponding estimates vary widely depending on how the sacrifice of two out of four hydrogen bonds is accounted for. Second, entropy differences between luminal and bulk water may arise: additional degrees of freedom caused by dangling OH-bonds increase entropy. At the same time, long-range dipolar water interactions decrease entropy. Here, we dissect different contributions to Gibbs free energy of activation, ΔG‡, for single-file water transport through narrow channels by analyzing experimental results from water permeability measurements on both bare lipid bilayers and biological water channels that (i) consider unstirred layer effects and (ii) adequately count the channels in reconstitution experiments. First, the functional relationship between water permeabilities and Arrhenius activation energies indicates negligible differences between the entropies of intraluminal water and bulk water. Second, we calculate ΔG‡ from unitary water channel permeabilities using transition state theory. Plotting ΔG‡ as a function of the number of H-bond donating or accepting pore-lining residues results in a 0.1 kcal/mol contribution per residue. The resulting upper limit for partial water dehydration amounts to 2 kcal/mol. In the framework of biomimicry, our analysis provides valuable insights for the design of synthetic water channels. It thus may aid in the urgent endeavor towards combating global water scarcity.
Meet the IUPAB Councilor—Hans-Joachim Galla
Authors: Galla Hans-Joachim
Published: November 2021

As one of the twelve Councilors, it is my pleasure to provide a short biographical sketch for the readers of Biophys. Rev. and for the members of the Biophysical Societies. I have been a member of the council in the former election period. Moreover, I served since decades in the German Biophysical Society (DGfB) as board member, secretary, vice president, and president. I hold a diploma degree in chemistry as well as PhD from the University of Göttingen. The experimental work for both qualifications has been performed at the Max Planck Institute for Biophysical Chemistry in Göttingen under the guidance of Erich Sackmann and the late Herman Träuble. When E. Sackmann moved to the University of Ulm, I joined his group as a research assistant performing my independent research on structure and dynamics of biological and artificial membranes and qualified for the “habilitation” thesis in Biophysical Chemistry. I have spent a research year at Stanford University supported by the Deutsche Forschungsgemeinschaft (DFG) and after coming back to Germany, I was appointed as a Heisenberg Fellow by the DFG and became Professor in Biophysical Chemistry in the Chemistry Department of the University of Darmstadt. Since 1990, I spent my career at the Institute for Biochemistry of the University of Muenster as full Professor and Director of the institute. I have trained numerous undergraduate, 150 graduate, and postdoctoral students from chemistry, physics, and also pharmacy as well as biology resulting in more than 350 published papers including reviews and book articles in excellent collaboration with colleagues from different academic disciplines in our university and also internationally, e.g., as a guest professor at the Chemistry Department of the Chinese Academy of Science in Beijing.
A method to optimize the length of flexible hose of the radial jet drilling technology
Authors: Hu Zhifang , Yue Weimin , Chi Huanpeng , Xue Zongan , Tang Guanwei , Zhang Xinyu
Published: November 2021

Radial jet drilling (RJD) technology has been applied to enhance the recovery of difficult-to-produce reserves by multiple horizontal micro-holes. The micro-hole length drilled by high-pressure water jets is of vital importance for the oil and gas recovery effect and is usually tens of meters long for applications in maturing oil fields in China. The water jets are generated by multiple orifices nozzle generally. Many studies focused on improving the self-propelled force generated by water jets to increase the micro-hole length. However, there are few researches on improving the micro-hole extension capacity in terms of optimizing the flexible hose that acts as the drill pipe in conventional drilling technology. This paper firstly studied the relationship between the flexible hose length and the micro-hole extension limit according to the analytical model to calculate the micro-hole extension limit. Then, the method to optimize the flexible hose length and the flow rate was developed aiming to obtain maximum micro-hole extension limit. The results show that the micro-hole extension limit decreases logarithmically with the increase in the flexible hose length under the condition that the takes the maximum value. The optimization model is applied by a field case and is proved to be effective to increase the micro-hole extension limit. This study is significant to improve the micro-hole extension capacity. Moreover, it provides a reference for the design of the hydraulics and selection of flexible hose for the RJD.
So different yet so alike: micro and macro labour market outcomes in Germany and Spain
Authors: Güell Maia , Lafuente Cristina , Sánchez Manuel , Turon Hélène
Published: November 2021

It is well known that German and Spanish labour markets are quite different from a macro point of view. In this paper, we look at these markets through the lenses of individual unstable spells. These include all forms of atypical employment (such as temporary contracts and mini-jobs) as well as unemployment. This combined unstable state captures a fuller picture of the individual experience of volatile income and uncertain employment status than unemployment alone. We find that the survival rates of unstable spells in the two countries are much more similar than those from unemployment. This suggests that the usual focus on unemployment stocks and durations exaggerates the contrast between the two countries in terms of workers’ experience of instability. We place these findings in the context of very similar aggregate shocks in the two countries and different policy choices on labour market reforms.
Application of VR technology in the aircraft cabin design process
Authors: Moerland-Masic Ivana , Reimer Fabian , Bock Thomas M. , Meller Frank , Nagel Björn
Published: November 2021

This paper addresses issues currently present in the aircraft cabin design process. It focuses on making the design process more time and cost efficient, while altogether involving the end-users (passengers and cabin crew) in the development process in its earliest stages. By understanding the underlying issues and reasons the cabin is developed according to the current approach, new methods are established and adapted to suit the needs of such a complex process. In this paper, the preposition is made that Virtual Reality is the key technology for achieving the following goals: shortening the initial cabin design process (from sketch to concept design) and including the end-users and their wishes and ideas into the ideation phase. Through cooperation with an external design agency, a Virtual Reality tool is implemented and tested to ensure the theory behind the established design methodology can also be put into practice.
On the Tits–Weiss conjecture and the Kneser–Tits conjecture for and (With an Appendix by R. M. Weiss)
Authors: Alsaody Seidon , Chernousov Vladimir , Pianzola Arturo
Published: November 2021

We prove that the structure group of any Albert algebra over an arbitrary field isR-trivial. This implies the Tits–Weiss conjecture for Albert algebras and the Kneser–Tits conjecture for isotropic groups of type$\mathrm {E}_{7,1}^{78}, \mathrm {E}_{8,2}^{78}$. As a further corollary, we show that some standard conjectures on the groups ofR-equivalence classes in algebraic groups and the norm principle are true for strongly inner forms of type$^1\mathrm {E}_6$.
Boundary layer dynamics and bottom friction in combined wave–current flows over large roughness elements
Authors: Yu Xiao , Rosman Johanna H. , Hench James L.
Published: November 2021

In the coastal ocean, interactions of waves and currents with large roughness elements, similar in size to wave orbital excursions, generate drag and dissipate energy. These boundary layer dynamics differ significantly from well-studied small-scale roughness. To address this problem, we derived spatially and phase-averaged momentum equations for combined wave–current flows over rough bottoms, including the canopy layer containing obstacles. These equations were decomposed into steady and oscillatory parts to investigate the effects of waves on currents, and currents on waves. We applied this framework to analyse large-eddy simulations of combined oscillatory and steady flows over hemisphere arrays (diameter$D$), in which current ($U_c$), wave velocity ($U_w$) and period ($T$) were varied. In the steady momentum budget, waves increase drag on the current, and this is balanced by the total stress at the canopy top. Dispersive stresses from oscillatory flow around obstacles are increasingly important as$U_w/U_c$increases. In the oscillatory momentum budget, acceleration in the canopy is balanced by pressure gradient, added-mass and form drag forces; stress gradients are small compared to other terms. Form drag is increasingly important as the Keulegan–Carpenter number$KC=U_wT/D$and$U_c/U_w$increase. Decomposing the drag term illustrates that a quadratic relationship predicts the observed dependences of steady and oscillatory drag on$U_c/U_w$and$KC$. For large roughness elements, bottom friction is well represented by a friction factor ($f_w$) defined using combined wave and current velocities in the canopy layer, which is proportional to drag coefficient and frontal area per unit plan area, and increases with$KC$and$U_c/U_w$.
Global electromagnetic turbulence simulations of W7-X-like plasmas with GENE-3D
Authors: Wilms Felix , Navarro Alejandro Bañón , Merlo Gabriele , Leppin Leonhard , Görler Tobias , Dannert Tilman , Hindenlang Florian , Jenko Frank
Published: November 2021

The GENE-3D code, the global stellarator version of the established GENE framework, has been extended to an electromagnetic gyrokinetic code. This paper outlines the basic structure of the algorithm, highlighting the treatment of the electromagnetic terms. The numerical implementation is verified against the radially global GENE code in linear and nonlinear tokamak simulations, recovering excellent agreement between both codes. As a first application to stellarator plasmas, linear and nonlinear global simulations with kinetic electrons of ion temperature gradient (ITG) turbulence in Wendelstein 7-X were performed, showing a decrease of ITG activity through the introduction of electromagnetic effects via a finite plasma-

$\beta$

. The upgrade makes it possible to study a large variety of new physical scenarios, including kinetic electron and electromagnetic effects, reducing the gap between gyrokinetic models and physically realistic systems.
Change in impulsivity is prospectively associated with treatment outcomes for binge-eating disorder
Authors: Boswell Rebecca G. , Gueorguieva Ralitza , Grilo Carlos M.
Published: November 2021

Background

Impulsivity may be a process underlying binge-eating disorder (BED) psychopathology and its treatment. This study examined change in impulsivity during cognitive-behavioral therapy (CBT) and/or pharmacological treatment for BED and associations with treatment outcomes.

Methods

In total, 108 patients with BED (NFEMALE = 84) in a randomized placebo-controlled clinical trial evaluating the efficacy of CBT and/or fluoxetine were assessed before treatment, monthly throughout treatment, at post-treatment (16 weeks), and at 12-month follow-up after completing treatment. Patients completed established measures of impulsivity, eating-disorder psychopathology, and depression, and were measured for height and weight [to calculate body mass index (BMI)] during repeated assessments by trained/monitored doctoral research-clinicians. Mixed-effects models using all available data examined changes in impulsivity and the association of rapid and overall changes in impulsivity on treatment outcomes. Exploratory analyses examined whether baseline impulsivity predicted/moderated outcomes.

Results

Impulsivity declined significantly throughout treatment and follow-up across treatment groups. Rapid change in impulsivity and overall change in impulsivity during treatment were significantly associated with reductions in eating-disorder psychopathology, depression scores, and BMI during treatment and at post-treatment. Overall change in impulsivity during treatment was associated with subsequent reductions in depression scores at 12-month follow-up. Baseline impulsivity did not moderate/predict eating-disorder outcomes or BMI but did predict change in depression scores.

Conclusions

Rapid and overall reductions in impulsivity during treatment were associated with improvements in specific eating-disorder psychopathology and associated general outcomes. These effects were found for both CBT and pharmacological treatment for BED. Change in impulsivity may be an important process prospectively related to treatment outcome.
Financial abuse of older people by third parties in banking institutions: a qualitative exploration
Authors: Phelan Amanda , O'Donnell Deirdre , McCarthy Sandra
Published: November 2021

Financial abuse is a significant form of elder maltreatment and is frequently ranked in the top two most common forms of abuse perpetration. Despite this, it is under-identified, under-reported and under-prosecuted. Financial institutions, such as banks, are important environments for identifying and responding to the financial abuse of older people. Traditionally, banks have not always been part of inter-sectorial responses to financial abuse, yet are important stakeholders. The aim of this study is to explore perceptions and experiences of financial abuse in five national banks. Data were collected from 20 bank managers and five members of the National Safeguarding Committee in the Republic of Ireland. Using thematic analysis, four themes were identified: defining a vulnerable adult; cases of financial abuse of vulnerable adults; case responses to financial abuse of vulnerable adults; and contextual issues. The data demonstrate the multiplicity of manifestations and the complexity of case investigation and management. Findings point to the need to enhance banks’ responses, through additional education and training, and promote integrated inter-sectorial collaboration. In addition, a change in societal beliefs is needed regarding financial entitlement, responding to ageism, public awareness of the consequences of financial decisions and types of financial abuse, as well as ensuring such crimes are addressed within the legal system.
Women, Violence, and Gender Dynamics during and after the Five Patani-Siam Wars, 1785–1838
Authors: Bradley Francis R.
Published: November 2021

This article examines five wars that occurred on the Malay-Thai Peninsula in the period 1785–1838 and the deep impact they had upon women's lives during and after the conflicts. Constituting the majority of surviving refugees, women rebuilt their lives in the wake of war through business and trade in Malaya, as Islamic teachers in Mecca and Southeast Asia, and as servants and slaves in Bangkok. In each of these settings, women encountered new forms of agency and newfound challenges, shifting cultural values that regulated decisions and actions, and evolving perceptions of the qualifications for leadership. Focused upon the political demise of the Patani Sultanate, a state with a long history of female rule, this study is of particular relevance to scholarly debates concerning women in contemporary warfare because of its transnational focus with keen attention to women in a variety of Islamic spaces and contexts, its aim of dispelling the pervasive notion of Muslim women as lacking agency, and as a point of comparison for the present armed conflict still raging in Southern Thailand that has claimed more than five thousand and continues to impact women and gender dynamics in the region.
Boreal Headwater Catchment as Hot Spot of Carbon Processing From Headwater to Fjord
Authors: Clayer F. , Thrane J.‐E. , Brandt U. , Dörsch P. , de Wit H. A.
Published: November 2021

Boreal headwaters and aquatic sediments are significant transporters, stores and processors of terrestrial carbon (C) as well as emitters of greenhouse gases (GHGs), mainly CO2 and CH4. While terrestrial ecosystems are net sinks of atmospheric C, lateral fluxes of total organic and dissolved inorganic C (TOC, DIC) as well as GHG release can significantly reduce the land C sink. However, the fate of the laterally exported C remains often unresolved. Here, we combine datasets from high‐frequency sensors, monitoring and modeling to produce a C budget for a typical boreal lake and its catchment and examine it in a regional context. We show that lake TOC removal is dominated by microbial metabolism which shows strong seasonal fluctuations following stratification and ice‐cover dynamics. We estimate that 11.5 g C m−2 catchment yr−1 are exported from the catchment soils and wetlands, including 9.5 g of TOC. Only 5.4 g C m−2 catchment yr−1 reach the coast while over 50% is reemitted to the atmosphere (5.7 g C m−2 catchment yr−1). Part of the reemitted C originates from rapid turnover cycles and would not affect atmospheric CO2 and the land C sink. However, we show that the land C sink at Langtjern is reduced by >14% over the whole aquatic continuum, and by >10% within the headwater catchment. Our regional analysis suggests that headwater lake TOC mineralization is the main TOC loss along the aquatic continuum with burial being relatively small, and highlights the significance of small headwaters as intensive and fast‐responding TOC processors.
Neurological complications and infection mechanism of SARS-CoV-2
Authors: Wan Dandan , Du Tingfu , Hong Weiqi , Chen Li , Que Haiying , Lu Shuaiyao , Peng Xiaozhong
Published: November 2021

Currently, SARS-CoV-2 has caused a global pandemic and threatened many lives. Although SARS-CoV-2 mainly causes respiratory diseases, growing data indicate that SARS-CoV-2 can also invade the central nervous system (CNS) and peripheral nervous system (PNS) causing multiple neurological diseases, such as encephalitis, encephalopathy, Guillain-Barré syndrome, meningitis, and skeletal muscular symptoms. Despite the increasing incidences of clinical neurological complications of SARS-CoV-2, the precise neuroinvasion mechanisms of SARS-CoV-2 have not been fully established. In this review, we primarily describe the clinical neurological complications associated with SARS-CoV-2 and discuss the potential mechanisms through which SARS-CoV-2 invades the brain based on the current evidence. Finally, we summarize the experimental models were used to study SARS-CoV-2 neuroinvasion. These data form the basis for studies on the significance of SARS-CoV-2 infection in the brain.
'You had to do something': prescribing antibiotics in Scotland during the COVID-19 pandemic restrictions and remobilisation
Authors: Duncan Eilidh M. , Goulao Beatriz , Clarkson Janet , Young Linda , Ramsay Craig R.
Published: November 2021

Introduction The COVID-19 pandemic brought about seismic change for dentistry including the direction to provide remote advice and prescribe analgesia and antimicrobials. The possibilities for care have widened, but the impact of both restrictions and remobilisation on antibiotic prescribing is not known.

Aims To report the impact of COVID-19 restrictions and remobilisation on dental antibiotic prescriptions and explore dentists' intentions and attitudes towards antibiotic prescribing.

Design and setting Public Health Scotland national prescribing and claims data are reported alongside an online survey of Scottish general and public health service dentists including closed and open-ended questions.

Results Antibiotic prescribing rose by 49% following the suspension of routine dental care, to a peak of 34,993 antibiotics (July 2020). The data also show that since the remobilisation of NHS dental care, antibiotic prescribing remains raised at levels around 28% higher than pre-pandemic. The survey highlights dentists' frustrations and concerns about this increased use of antibiotics. Most dentists intend to reduce their prescribing; however, significant challenges to this being realised were raised.

Conclusions The previous success within dentistry to protect against the development of antimicrobial resistance has suffered a knock-back during the pandemic. A renewed focus on reducing unnecessary antibiotics within dentistry is required but, crucially, needs to be approached sensitively alongside the current backdrop of challenges within the service.
At the dawn: cell-free DNA fragmentomics and gene regulation
Authors: Liu Yaping
Published: November 2021

Epigenetic mechanisms play instrumental roles in gene regulation during embryonic development and disease progression. However, it is challenging to non-invasively monitor the dynamics of epigenomes and related gene regulation at inaccessible human tissues, such as tumours, fetuses and transplanted organs. Circulating cell-free DNA (cfDNA) in peripheral blood provides a promising opportunity to non-invasively monitor the genomes from these inaccessible tissues. The fragmentation patterns of plasma cfDNA are unevenly distributed in the genome and reflect the in vivo gene-regulation status across multiple molecular layers, such as nucleosome positioning and gene expression. In this review, we revisited the computational and experimental approaches that have been recently developed to measure the cfDNA fragmentomics across different resolutions comprehensively. Moreover, cfDNA in peripheral blood is released following cell death, after apoptosis or necrosis, mainly from haematopoietic cells in healthy people and diseased tissues in patients. Several cfDNA-fragmentomics approaches showed the potential to identify the tissues-of-origin in cfDNA from cancer patients and healthy individuals. Overall, these studies paved the road for cfDNA fragmentomics to non-invasively monitor the in vivo gene-regulatory dynamics in both peripheral immune cells and diseased tissues.
Lipid droplets contribute myogenic differentiation in C2C12 by promoting the remodeling of the acstin-filament
Authors: Tan Yanjie , Jin Yi , Zhao Pengxiang , Wu Jian , Ren Zhuqing
Published: November 2021

Lipid droplet (LD), a multi-functional organelle, is found in most eukaryotic cells. LDs participate in the regulation of many cellular processes including proliferation, stress, and apoptosis. Previous studies showed the athlete’s paradox that trained athletes accumulate LDs in their skeletal muscle. However, the impact of LDs on skeletal muscle and myogenesis is not clear. We discovered that C2C12 myoblast cells containing more LDs formed more multinucleated muscle fibers. We also discovered that LDs promoted cell migration and fusion by promoting actin-filaments remodeling. Mechanistically, two LD-proteins, Acyl-CoA synthetase long chain family member 3 (ACSL3) and lysophosphatidylcholine acyltransferase 1 (LPCAT1), medicated the recruitment of actinin proteins which contributed to actin-filaments formation on the surface of LDs. During remodeling, the actinin proteins on LDs surface translocated to actin-filaments via ARF1/COPI vesicles. Our study demonstrate LDs contribute to cell differentiation, which lead to new insight into the LD function.
Single-cell transcriptome profiling reveals intratumoural heterogeneity and malignant progression in retinoblastoma
Authors: Yang Jie , Li Yongyun , Han Yanping , Feng Yiyi , Zhou Min , Zong Chunyan , He Xiaoyu , Jia Renbing , Xu Xiaofang , Fan Jiayan
Published: November 2021

Retinoblastoma is a childhood retinal tumour that is the most common primary malignant intraocular tumour. However, it has been challenging to identify the cell types associated with genetic complexity. Here, we performed single-cell RNA sequencing on 14,739 cells from two retinoblastoma samples to delineate the heterogeneity and the underlying mechanism of retinoblastoma progression. Using a multiresolution network-based analysis, we identified two major cell types in human retinoblastoma. Cell trajectory analysis yielded a total of 5 cell states organized into two main branches, and the cell cycle-associated cone precursors were the cells of origin of retinoblastoma that were required for initiating the differentiation and malignancy process of retinoblastoma. Tumour cells differentiation reprogramming trajectory analysis revealed that cell-type components of multiple tumour-related pathways and predominantly expressed UBE2C were associated with an activation state in the malignant progression of the tumour, providing a potential novel “switch gene” marker during early critical stages in human retinoblastoma development. Thus, our findings improve our current understanding of the mechanism of retinoblastoma progression and are potentially valuable in providing novel prognostic markers for retinoblastoma.
circKDM4C enhances bladder cancer invasion and metastasis through miR-200bc-3p/ZEB1 axis
Authors: Ma Xueyou , Ying Yufan , Sun Jiazhu , Xie Haiyun , Li Jiangfeng , He Liujia , Wang Weiyu , Chen Shiming , Shen Haixiang , Yi Jiahe , Luo Jindan , Wang Xiao , Zheng Xiangyi , Liu Ben , Xie Liping
Published: November 2021

Circular RNAs (circRNAs) play essential roles in human bladder cancer (BCa) development, however, unusual expression patterns and functional dysfunction of circRNAs in BCa have not been evaluated. In this study, we validated that circKDM4C (hsa_circ_0001839), derived from the KDM4C gene, is elevated in BCa cell lines as well as tissues. Functionally, overexpression of circKDM4C significantly enhances, and silencing of circKDM4C suppresses migration and invasion capabilities of BCa cells. Mechanistically, circKDM4C can directly interact with miR-200b-3p and miR-200c-3p as a miRNA sponge, which enhances the expression of ZEB1 and promotes ﻿mesenchymal phenotype. Conclusively, our findings indicate that circKDM4C may act as a pro-oncogenic factor in BCa invasion and metastasis via the circKDM4C/miR-200bc-3p/ZEB1 axis, which is a potential biomarker or therapeutic target for bladder cancer.
Receptor interacting protein 3 kinase, not 1 kinase, through MLKL-mediated necroptosis is involved in UVA-induced corneal endothelium cell death
Authors: Yu Zhen , Efstathiou Nikolaos E. , Correa Victor S. M. C. , Chen Xiaohong , Ishihara Kenji , Iesato Yasuhiro , Narimatsu Toshio , Ntentakis Dimitrios , Chen Yanyun , Vavvas Demetrios G.
Published: November 2021

Ultraviolet (UV) is one of the most energetic radiations in the solar spectrum that can result in various tissue injury disorders. Previous studies demonstrated that UVA, which represents 95% of incident photovoltaic radiation, induces corneal endothelial cells (CECs) death. Programmed cell death (PCD) has been implicated in numerous ophthalmologic diseases. Here, we investigated receptor-interacting protein 3 kinase (RIPK3), a key signaling molecule of PCD, in UVA-induced injury using a short-term corneal endothelium (CE) culture model. UVA irradiation activated RIPK3 and mediated necroptosis both in mouse CE and primary human CECs (pHCECs). UVA irradiation was associated with upregulation of key necroptotic molecules (DAI, TRIF, and MLKL) that lie downstream of RIPK3. Moreover, RIPK3 inhibition or silencing in primary corneal endothelial cells suppresses UVA-induced cell death, along with downregulation of MLKL in pHCECs. In addition, genetic inhibition or knockout of RIPK3 in mice (RIPK3K51A and RIPK3−/− mice) similarly attenuates cell death and the levels of necroptosis in ex vivo UVA irradiation experiments. In conclusion, these results identify RIPK3, not RIPK1, as a critical regulator of UVA-induced cell death in CE and indicate its potential as a future protective target.
Spatial and temporal intratumour heterogeneity has potential consequences for single biopsy-based neuroblastoma treatment decisions
Authors: Schmelz Karin , Toedling Joern , Huska Matt , Cwikla Maja C. , Kruetzfeldt Louisa-Marie , Proba Jutta , Ambros Peter F. , Ambros Inge M. , Boral Sengül , Lodrini Marco , Chen Celine Y. , Burkert Martin , Guergen Dennis , Szymansky Annabell , Astrahantseff Kathy , Kuenkele Annette , Haase Kerstin , Fischer Matthias , Deubzer Hedwig E. , Hertwig Falk , Hundsdoerfer Patrick , Henssen Anton G. , Schwarz Roland F. , Schulte Johannes H. , Eggert Angelika
Published: November 2021

Intratumour heterogeneity is a major cause of treatment failure in cancer. We present in-depth analyses combining transcriptomic and genomic profiling with ultra-deep targeted sequencing of multiregional biopsies in 10 patients with neuroblastoma, a devastating childhood tumour. We observe high spatial and temporal heterogeneity in somatic mutations and somatic copy-number alterations which are reflected on the transcriptomic level. Mutations in some druggable target genes including ALK and FGFR1 are heterogeneous at diagnosis and/or relapse, raising the issue whether current target prioritization and molecular risk stratification procedures in single biopsies are sufficiently reliable for therapy decisions. The genetic heterogeneity in gene mutations and chromosome aberrations observed in deep analyses from patient courses suggest clonal evolution before treatment and under treatment pressure, and support early emergence of metastatic clones and ongoing chromosomal instability during disease evolution. We report continuous clonal evolution on mutational and copy number levels in neuroblastoma, and detail its implications for therapy selection, risk stratification and therapy resistance.
The mechanics of landslide mobility with erosion
Authors: Pudasaini Shiva P. , Krautblatter Michael
Published: November 2021

Erosion can significantly increase the destructive power of a landslide by amplifying its volume, mobility and impact force. The threat posed by an erosive landslide is linked to its mobility. No mechanical condition has yet been presented for when, how and how much energy erosive landslides gain or lose. Here, we pioneer a mechanical model for the energy budget of erosive landslides that controls enhanced or reduced mobility. Inertia is related to an entrainment velocity, is a fundamentally new understanding. This ascertains the true inertia of erosive landslides, making a breakthrough in correctly determining the landslide mobility. Erosion velocity, which regulates the energy budget, determines the enhanced or reduced mobility. Newly developed energy generator offers the first-ever mechanical quantification of erosional energy and a precise description of mobility. This addresses the long-standing question of why many erosive landslides generate higher mobility, while others reduce mobility. We demonstrate that erosion and entrainment are different processes. Landslides gain energy and enhance mobility if the erosion velocity exceeds the entrainment velocity. Energy velocity delineates distinct excess energy regimes. Newly introduced mobility scaling and erosion number deliver the explicit measure of mobility. Presented dynamical equations correctly include erosion induced net momentum production.
ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury
Authors: Yamaguchi Tomokazu , Hoshizaki Midori , Minato Takafumi , Nirasawa Satoru , Asaka Masamitsu N. , Niiyama Mayumi , Imai Masaki , Uda Akihiko , Chan Jasper Fuk-Woo , Takahashi Saori , An Jianbo , Saku Akari , Nukiwa Ryota , Utsumi Daichi , Kiso Maki , Yasuhara Atsuhiro , Poon Vincent Kwok-Man , Chan Chris Chung-Sing , Fujino Yuji , Motoyama Satoru , Nagata Satoshi , Penninger Josef M. , Kamada Haruhiko , Yuen Kwok-Yung , Kamitani Wataru , Maeda Ken , Kawaoka Yoshihiro , Yasutomi Yasuhiro , Imai Yumiko , Kuba Keiji
Published: November 2021

Angiotensin-converting enzyme 2 (ACE2) is a receptor for cell entry of SARS-CoV-2, and recombinant soluble ACE2 protein inhibits SARS-CoV-2 infection as a decoy. ACE2 is a carboxypeptidase that degrades angiotensin II, thereby improving the pathologies of cardiovascular disease or acute lung injury. Here we show that B38-CAP, an ACE2-like enzyme, is protective against SARS-CoV-2-induced lung injury. Endogenous ACE2 expression is downregulated in the lungs of SARS-CoV-2-infected hamsters, leading to elevation of angiotensin II levels. Recombinant Spike also downregulates ACE2 expression and worsens the symptoms of acid-induced lung injury. B38-CAP does not neutralize cell entry of SARS-CoV-2. However, B38-CAP treatment improves the pathologies of Spike-augmented acid-induced lung injury. In SARS-CoV-2-infected hamsters or human ACE2 transgenic mice, B38-CAP significantly improves lung edema and pathologies of lung injury. These results provide the first in vivo evidence that increasing ACE2-like enzymatic activity is a potential therapeutic strategy to alleviate lung pathologies in COVID-19 patients.
Developmental decrease of entorhinal-hippocampal communication in immune-challenged DISC1 knockdown mice
Authors: Xu Xiaxia , Song Lingzhen , Kringel Rebecca , Hanganu-Opatz Ileana L.
Published: November 2021

The prefrontal-hippocampal dysfunction that underlies cognitive deficits in mental disorders emerges during early development. The lateral entorhinal cortex (LEC) is tightly interconnected with both prefrontal cortex (PFC) and hippocampus (HP), yet its contribution to the early dysfunction is fully unknown. Here we show that mice that mimic the dual genetic (G) -environmental (E) etiology (GE mice) of psychiatric risk have poor LEC-dependent recognition memory at pre-juvenile age and abnormal communication within LEC-HP-PFC networks throughout development. These functional and behavioral deficits relate to sparser projections from LEC to CA1 and decreased efficiency of axonal terminals to activate the hippocampal circuits in neonatal GE mice. In contrast, the direct entorhinal drive to PFC is not affected, yet the PFC is indirectly compromised, as target of the under-activated HP. Thus, the entorhinal-hippocampal circuit is already impaired from neonatal age on in GE mice.
Structure of the class C orphan GPCR GPR158 in complex with RGS7-Gβ5
Authors: Jeong Eunyoung , Kim Yoojoong , Jeong Jihong , Cho Yunje
Published: November 2021

GPR158, a class C orphan GPCR, functions in cognition, stress-induced mood control, and synaptic development. Among class C GPCRs, GPR158 is unique as it lacks a Venus flytrap-fold ligand-binding domain and terminates Gαi/o protein signaling through the RGS7-Gβ5 heterodimer. Here, we report the cryo-EM structures of GPR158 alone and in complex with one or two RGS7-Gβ5 heterodimers. GPR158 dimerizes through Per-Arnt-Sim-fold extracellular and transmembrane (TM) domains connected by an epidermal growth factor-like linker. The TM domain (TMD) reflects both inactive and active states of other class C GPCRs: a compact intracellular TMD, conformations of the two intracellular loops (ICLs) and the TMD interface formed by TM4/5. The ICL2, ICL3, TM3, and first helix of the cytoplasmic coiled-coil provide a platform for the DHEX domain of one RGS7 and the second helix recruits another RGS7. The unique features of the RGS7-binding site underlie the selectivity of GPR158 for RGS7.
Naked mole-rat brown fat thermogenesis is diminished during hypoxia through a rapid decrease in UCP1
Authors: Cheng Hang , Sebaa Rajaa , Malholtra Nikita , Lacoste Baptiste , El Hankouri Ziyad , Kirby Alexia , Bennett Nigel C. , van Jaarsveld Barry , Hart Daniel W. , Tattersall Glenn J. , Harper Mary-Ellen , Pamenter Matthew E.
Published: November 2021

Naked mole-rats are among the most hypoxia-tolerant mammals. During hypoxia, their body temperature (Tb) decreases via unknown mechanisms to conserve energy. In small mammals, non-shivering thermogenesis in brown adipose tissue (BAT) is critical to Tb regulation; therefore, we hypothesize that hypoxia decreases naked mole-rat BAT thermogenesis. To test this, we measure changes in Tb during normoxia and hypoxia (7% O2; 1–3 h). We report that interscapular thermogenesis is high in normoxia but ceases during hypoxia, and Tb decreases. Furthermore, in BAT from animals treated in hypoxia, UCP1 and mitochondrial complexes I-V protein expression rapidly decrease, while mitochondria undergo fission, and apoptosis and mitophagy are inhibited. Finally, UCP1 expression decreases in hypoxia in three other social African mole-rat species, but not a solitary species. These findings suggest that the ability to rapidly down-regulate thermogenesis to conserve oxygen in hypoxia may have evolved preferentially in social species.
Monthly direct and indirect greenhouse gases emissions from household consumption in the major Japanese cities
Authors: Long Yin , Jiang Yida , Chen Peipei , Yoshida Yoshikuni , Sharifi Ayyoob , Gasparatos Alexandros , Wu Yi , Kanemoto Keiichiro , Shigetomi Yosuke , Guan Dabo
Published: November 2021

Urban household consumption contributes substantially to global greenhouse gases (GHGs) emissions. Urban household emissions encompass both direct and indirect emissions, with the former associated with the direct use of fossil fuels and the latter with the emissions embodied in the consumed goods and services. However, there is a lack of consistent and comprehensive datasets outlining in great detail emissions from urban household consumption. To bridge this data gap, we construct an emission inventory of urban household emissions for 52 major cities in Japan that covers around 500 emission categories. The dataset spans from January 2011 to December 2015 and contains 12,384 data records for direct emissions and 1,543,128 records for indirect emissions. Direct emission intensity is provided in g-CO2/JPY to facilitate both future studies of household emission in Japan, as well as act as a reference for the development of detailed household emission inventories in other countries.
The encapsulin from Thermotoga maritima is a flavoprotein with a symmetry matched ferritin-like cargo protein
Authors: LaFrance Benjamin J. , Cassidy-Amstutz Caleb , Nichols Robert J. , Oltrogge Luke M. , Nogales Eva , Savage David F.
Published: November 2021

Bacterial nanocompartments, also known as encapsulins, are an emerging class of protein-based ‘organelles’ found in bacteria and archaea. Encapsulins are virus-like icosahedral particles comprising a ~ 25–50 nm shell surrounding a specific cargo enzyme. Compartmentalization is thought to create a unique chemical environment to facilitate catalysis and isolate toxic intermediates. Many questions regarding nanocompartment structure–function remain unanswered, including how shell symmetry dictates cargo loading and to what extent the shell facilitates enzymatic activity. Here, we explore these questions using the model Thermotoga maritima nanocompartment known to encapsulate a redox-active ferritin-like protein. Biochemical analysis revealed the encapsulin shell to possess a flavin binding site located at the interface between capsomere subunits, suggesting the shell may play a direct and active role in the function of the encapsulated cargo. Furthermore, we used cryo-EM to show that cargo proteins use a form of symmetry-matching to facilitate encapsulation and define stoichiometry. In the case of the Thermotoga maritima encapsulin, the decameric cargo protein with fivefold symmetry preferentially binds to the pentameric-axis of the icosahedral shell. Taken together, these observations suggest the shell is not simply a passive barrier—it also plays a significant role in the structure and function of the cargo enzyme.
Nanovibrational stimulation inhibits osteoclastogenesis and enhances osteogenesis in co-cultures
Authors: Kennedy Ian W. , Tsimbouri P. Monica , Campsie Paul , Sood Shatakshi , Childs Peter G. , Reid Stuart , Young Peter S. , Meek Dominic R. M. , Goodyear Carl S. , Dalby Matthew J.
Published: November 2021

Models of bone remodelling could be useful in drug discovery, particularly if the model is one that replicates bone regeneration with reduction in osteoclast activity. Here we use nanovibrational stimulation to achieve this in a 3D co-culture of primary human osteoprogenitor and osteoclast progenitor cells. We show that 1000 Hz frequency, 40 nm amplitude vibration reduces osteoclast formation and activity in human mononuclear CD14+ blood cells. Additionally, this nanoscale vibration both enhances osteogenesis and reduces osteoclastogenesis in a co-culture of primary human bone marrow stromal cells and bone marrow hematopoietic cells. Further, we use metabolomics to identify Akt (protein kinase C) as a potential mediator. Akt is known to be involved in bone differentiation via transforming growth factor beta 1 (TGFβ1) and bone morphogenetic protein 2 (BMP2) and it has been implicated in reduced osteoclast activity via Guanine nucleotide-binding protein subunit α13 (Gα13). With further validation, our nanovibrational bioreactor could be used to help provide humanised 3D models for drug screening.
Assessment of CT to CBCT contour mapping for radiomic feature analysis in prostate cancer
Authors: Schmidt Ryder M. , Delgadillo Rodrigo , Ford John C. , Padgett Kyle R. , Studenski Matthew , Abramowitz Matthew C. , Spieler Benjamin , Xu Yihang , Yang Fei , Dogan Nesrin
Published: November 2021

This study provides a quantitative assessment of the accuracy of a commercially available deformable image registration (DIR) algorithm to automatically generate prostate contours and additionally investigates the robustness of radiomic features to differing contours. Twenty-eight prostate cancer patients enrolled on an institutional review board (IRB) approved protocol were selected. Planning CTs (pCTs) were deformably registered to daily cone-beam CTs (CBCTs) to generate prostate contours (auto contours). The prostate contours were also manually drawn by a physician. Quantitative assessment of deformed versus manually drawn prostate contours on daily CBCT images was performed using Dice similarity coefficient (DSC), mean distance-to-agreement (MDA), difference in center-of-mass position (ΔCM) and difference in volume (ΔVol). Radiomic features from 6 classes were extracted from each contour. Lin’s concordance correlation coefficient (CCC) and mean absolute percent difference in radiomic feature-derived data (mean |%Δ|RF) between auto and manual contours were calculated. The mean (± SD) DSC, MDA, ΔCM and ΔVol between the auto and manual prostate contours were 0.90 ± 0.04, 1.81 ± 0.47 mm, 2.17 ± 1.26 mm and 5.1 ± 4.1% respectively. Of the 1,010 fractions under consideration, 94.8% of DIRs were within TG-132 recommended tolerance. 30 radiomic features had a CCC > 0.90 and 21 had a mean |%∆|RF < 5%. Auto-propagation of prostate contours resulted in nearly 95% of DIRs within tolerance recommendations of TG-132, leading to the majority of features being regarded as acceptably robust. The use of auto contours for radiomic feature analysis is promising but must be done with caution.
A proximity proteomics screen in three-dimensional spheroid cultures identifies novel regulators of lumen formation
Authors: Wang Li-Ting , Proulx Marie-Ève , Kim Anne D. , Lelarge Virginie , McCaffrey Luke
Published: November 2021

Apical-basal cell polarity and lumen formation are essential features of many epithelial tissues, which are disrupted in diseases like cancer. Here, we describe a proteomics-based screen to identify proteins involved in lumen formation in three-dimensional spheroid cultures. We established a suspension-based culture method suitable for generating polarized cysts in sufficient quantities for proteomic analysis. Using this approach, we identified several known and unknown proteins proximally associated with PAR6B, an apical protein involved in lumen formation. Functional analyses of candidates identified PARD3B (a homolog of PARD3), RALB, and HRNR as regulators of lumen formation. We also identified PTPN14 as a component of the Par-complex that is required for fidelity of apical-basal polarity. Cells transformed with KRASG12Vexhibit lumen collapse/filling concomitant with disruption of the Par-complex and down-regulation of PTPN14. Enforced expression of PTPN14 maintained the lumen and restricted the transformed phenotype in KRASG12V-expressing cells. This represents an applicable approach to explore protein–protein interactions in three-dimensional culture and to identify proteins important for lumen maintenance in normal and oncogene-expressing cells.
Novel non intrusive continuous use ZeBox technology to trap and kill airborne microbes
Authors: Phadke Kruttika S. , Madival Deepak G. , Venkataraman Janani , Kundu Debosmita , Ramanujan K. S. , Holla Nisha , Arakeri Jaywant , Tomar Gaurav , Datta Santanu , Ghatak Arindam
Published: November 2021

Preventing nosocomial infection is a major unmet need of our times. Existing air decontamination technologies suffer from demerits such as toxicity of exposure, species specificity, noxious gas emission, environment-dependent performance and high power consumption. Here, we present a novel technology called “ZeBox” that transcends the conventional limitations and achieves high microbicidal efficiency. In ZeBox, a non-ionizing electric field extracts naturally charged microbes from flowing air and deposits them on engineered microbicidal surfaces. The surface’s three dimensional topography traps the microbes long enough for them to be inactivated. The electric field and chemical surfaces synergistically achieve rapid inactivation of a broad spectrum of microbes. ZeBox achieved near complete kill of airborne microbes in challenge tests (5–9 log reduction) and $$>90\%$$

>
90
%

efficiency in a fully functional stem cell research facility in the presence of humans. Thus, ZeBox fulfills the dire need for a real-time, continuous, safe, trap-and-kill air decontamination technology.