bluuebunny/crossref_metadata_2025 huggingface dataset:
Balancing the length of distal tip is key for stability and signalling function of primary cilia
Authors: Kanamaru Taishi , Neuner Annett , Kurtulmus Bahtiyar , Pereira Gislene
Published: June 2021

Primary cilia are antenna-like organelles required for signalling transduction. How cilia structure is mechanistically maintained at steady-state to promote signalling is largely unknown. Here, we define that mammalian primary cilia are formed by middle and distal segments, in analogy to sensory cilia of lower eukaryotes. The analysis of middle/distal segmentation indicated that perturbations leading to cilia over-elongation influenced middle or distal segment length with a different impact on cilia behaviour. We identified Septins as novel repressors of distal segment growth. We show that Septins control the localisation of MKS3 and CEP290 required for a functional transition zone, and through this the entrance of the microtubule-capping kinesin KIF7, a cilia-growth inhibitor, into the cilium. Live-cell imaging and analysis of sonic-hedgehog (SHH) signalling activation established that distal segment over-extension increased cilia excision events and decreased SHH activation. Our data underlies the importance of understanding cilia segmentation for length control and cilia-dependent signalling.
Joint degeneration in a mouse model of pseudoachondroplasia: ER stress, inflammation and autophagy blockage
Authors: Hecht Jacqueline T. , Veerisetty Alka C. , Hossain Mohammad G. , Patra Debabrata , Chiu Frankie , Coustry Francoise , Posey Karen L.
Published: June 2021

Pseudoachondroplasia (PSACH), a short limb skeletal dysplasia, associated with premature joint degeneration is caused by misfolding mutations in cartilage oligomeric matrix protein (COMP). Here, we define mutant-COMP-induced stress mechanisms that occur in articular chondrocytes of MT-COMP mice, a murine model of PSACH. The accumulation of mutant-COMP in the ER occurred early in MT-COMP articular chondrocytes and stimulated inflammation (TNFα) at 4 wks. Articular chondrocyte death increased at 8 wks and ER stress through CHOP was elevated by 12 wks. Importantly, blockage of autophagy (pS6), the major mechanism which clears the ER, sustained cellular stress in MT-COMP articular chondrocytes. Degeneration of MT-COMP articular cartilage was similar to that observed in PSACH and was associated with increased MMPs, degradative enzymes. Moreover, chronic cellular stresses stimulated senescence. Senescence-associated secretory phenotype (SASP) may play a role in generating and propagating a pro-degradative environment in the MT-COMP murine joint. The loss of CHOP or resveratrol treatment from birth preserved joint health in MT-COMP mice. Taken together, these results indicate that ER stress/CHOP signaling and autophagy blockage are central to mutant-COMP joint degeneration and MT-COMP mice joint health can be preserved by decreasing articular chondrocyte stress. Future joint sparing therapeutics for PSACH may include resveratrol.
MiR-384 Regulates Reelin by Inhibiting ADAMTS4 in Neuronal Cell Lines
Authors: Cao Qiushi , Huang Bisheng , Wang Ping , Zhao Gang , Zhao Min , Yu Xiao-Ming
Published: June 2021

MicroRNAs (miRNAs) are important regulators of gene expression at the post-transcriptional level. The present study aims to investigate the role of miR-384 in Reelin by regulating ADAMTS4 in neuronal cell lines. Brain tissues from Aβ1-42 induced mouse model of Alzheimer’s disease and the control group were collected. RT-PCR, Western blotting and immunohistochemistry were performed to detect the levels of ADAMTS4 and miR-384 in tissues. Luciferase reporter assay, Western blotting and in vitro assay were used to validate that ADAMTS4 was the target gene of miR-384. Neuronal cell line, Neuro-2a, was selected for transfection assay. ADAMTS4 was significantly down-regulated in hippocampi of Alzheimer’s disease mouse model, and negatively correlated with miR-384. Then, ADAMTS4 was identified as a direct target of miR-384. Over-expressing of miR-384 in Neuro-2a showed that ADAMTS4 and the cleaved Reelin fragments were down regulated, and proliferation of neuronal cell lines (Neuro-2a and SH-SY5Y) were inhibited through DAB-1 pathway. In conclusion, these results revealed that miR-384 may play a regulatory role in Reelin via inhibiting ADAMTS4 in neuronal cell lines.
Single-cell intracellular pH dynamics regulate the cell cycle by timing G1 exit and the G2 transition
Authors: Spear Julia S. , White Katharine A.
Published: June 2021

Transient changes in intracellular pH (pHi) regulate normal cell behaviors, but roles for spatiotemporal pHi dynamics in single-cell behaviors remains unclear. Here, we mapped single-cell spatiotemporal pHi dynamics during mammalian cell cycle progression both with and without cell cycle synchronization. We found that single-cell pHi is dynamic throughout the cell cycle: pHi decreases at G1/S, increases in mid-S, decreases at late S, increases at G2/M, and rapidly decreases during mitosis. Importantly, while pHi is highly dynamic in dividing cells, non-dividing cells have attenuated pHi dynamics. Using two independent pHi manipulation methods, we found that low pHi inhibits completion of S phase while increased pHi promotes both S/G2 and G2/M transitions. Our data also suggest that low pHi cues G1 exit, with decreased pHi shortening G1 and increased pHi elongating G1. Furthermore, dynamic pHi is required for S phase timing, as high pHi elongates S phase and low pHi inhibits S/G2 transition. This work reveals spatiotemporal pHi dynamics are necessary for cell cycle progression at multiple phase transitions in single human cells.
STED super-resolution imaging of membrane packing and dynamics by exchangeable polarity-sensitive dyes
Authors: Carravilla Pablo , Dasgupta Anindita , Zhurgenbayeva Gaukhar , Danylchuk Dmytro I. , Klymchenko Andrey S. , Sezgin Erdinc , Eggeling Christian
Published: June 2021

Understanding the plasma membrane nano-scale organisation and dynamics in living cells requires microscopy techniques with high spatial and temporal resolution, permitting for long acquisition times, and that allow for the quantification of membrane biophysical properties such as lipid ordering. Among the most popular super-resolution techniques, stimulated emission depletion (STED) microscopy offers one of the highest temporal resolutions, ultimately defined by the scanning speed. However, monitoring live processes using STED microscopy is significantly limited by photobleaching, which recently has been circumvented by exchangeable membrane dyes that only temporarily reside in the membrane. Here, we show that NR4A, a polarity-sensitive exchangeable plasma membrane probe based on Nile Red, permits the super-resolved quantification of membrane biophysical parameters in real time with high temporal and spatial resolution as well as long acquisition times. The potential of this polarity-sensitive exchangeable dye is showcased by live-cell real-time 3D-STED recordings of bleb formation and lipid exchange during membrane fusion, as well as by STED-fluorescence correlation spectroscopy (STED-FCS) experiments for the simultaneous quantification of membrane dynamics and lipid packing, which correlate in model and live-cell membranes.
Numerical modeling of inverse problem of parameter identification for viscoelastic functionally graded materials/structures
Authors: Zhang Linlin , Yang Haitian
Published: June 2021

Purpose

This paper attempts to develop an efficient algorithm to solve the inverse problem of identifying constitutive parameters in VFG (viscoelastic functionally graded) materials/structures.

Design/methodology/approach

An adaptive recursive algorithm with high fidelity is developed to acquire the derivatives of displacements with respect to constitutive parameters, which are required for the accurate and stable gradient based inverse analysis. A two-step strategy is presented in the process of identification, by which the unknown parameters can be separately identified and the scale and complexity of the inverse VFG problem are reduced. At each step, the process of identification is treated as an optimization problem that is solved by the Levenberg–Marquardt method.

Findings

The solution accuracy of forward problems and derivatives of displacements can be stably achieved with different step sizes, and constitutive parameters of homogenous/regional-inhomogeneous VFG materials/structures can be effectively and accurately identified. By examining the reliability, resolution, impacts of reference information and noisy data, the effectiveness of the proposed approach is numerically verified via three numerical examples.

Originality/value

An adaptive recursive algorithm is developed for derivatives computing with high fidelity, providing a solid platform for the sensitivity analysis and thereby a two-step strategy in conjunction with Levenberg–Marquardt method is presented in the process of identification. Consequently, an effective algorithm is developed to identify constitutive parameters of homogenous/regional-inhomogeneous VFG materials/structures.
Applications of Bayesian approaches in construction management research: a systematic review
Authors: Hon Carol K.H. , Sun Chenjunyan , Xia Bo , Jimmieson Nerina L. , Way Kïrsten A. , Wu Paul Pao-Yen
Published: June 2021

Purpose

Bayesian approaches have been widely applied in construction management (CM) research due to their capacity to deal with uncertain and complicated problems. However, to date, there has been no systematic review of applications of Bayesian approaches in existing CM studies. This paper systematically reviews applications of Bayesian approaches in CM research and provides insights into potential benefits of this technique for driving innovation and productivity in the construction industry.

Design/methodology/approach

A total of 148 articles were retrieved for systematic review through two literature selection rounds.

Findings

Bayesian approaches have been widely applied to safety management and risk management. The Bayesian network (BN) was the most frequently employed Bayesian method. Elicitation from expert knowledge and case studies were the primary methods for BN development and validation, respectively. Prediction was the most popular type of reasoning with BNs. Research limitations in existing studies mainly related to not fully realizing the potential of Bayesian approaches in CM functional areas, over-reliance on expert knowledge for BN model development and lacking guides on BN model validation, together with pertinent recommendations for future research.

Originality/value

This systematic review contributes to providing a comprehensive understanding of the application of Bayesian approaches in CM research and highlights implications for future research and practice.
COVID-19 and the marginalized: an opinion piece on further measures to address COVID-19 in prisons in Sub-Saharan Africa
Authors: Katey Daniel , Morgan Anthony Kwame , Asori Moses , Ampofo Solomon Twum , Mpobi Robert Kwame Jumah
Published: June 2021

Purpose

This paper examines prison services and how they can be managed to uphold COVID-19 prevention etiquettes, in light of the contemporary rise in COVID-19 cases across the sub-Saharan Africa continent and the world at large.

Design/methodology/approach

An extensive review of existing literature on COVID-19 was conducted to ascertain the nature of the pandemic in prisons in sub-Saharan Africa.

Findings

In line with empirical observations, the paper recommends regular disinfection of prisons and correctional facilities on the sub-continent. Again, there is the need for countries to resort to alternative punitive measures other than imprisonment, to curb the issue of overcrowding in prisons. Furthermore, there is the need for national governments to build ultramodern prison facilities, which would make room for emergency situations, as well as make provision for any future rise in the number of inmates while, at the same time, meeting fundamental needs as peculiar to prisoners. Finally, medical units in prisons need to be well-equipped against contemporary rise in COVID-19 cases.

Originality/value

The authors hereby declare that this submission is their handmade which has not been submitted to any other journal outlet.
A control chart pattern recognition methodology for controlling information technology-enabled service (ITeS) process customer complaints
Authors: John Boby
Published: June 2021

Purpose

The purpose of this paper is to develop a control chart pattern recognition methodology for monitoring the weekly customer complaints of outsourced information technology-enabled service (ITeS) processes.

Design/methodology/approach

A two-step methodology is used to classify the processes as having natural or unnatural variation based on past 20 weeks' customer complaints. The step one is to simulate data on various control chart patterns namely natural variation, upward shift, upward trend, etc. Then a deep learning neural network model consisting of two dense layers is developed to classify the patterns as of natural or unnatural variation.

Findings

The validation of the methodology on telecom vertical processes has correctly detected unnatural variations in two terminated processes. The implementation of the methodology on banking and financial vertical processes has detected unnatural variation in one of the processes. This helped the company management to take remedial actions, renegotiate the deal and get it renewed for another period.

Practical implications

This study provides valuable information on controlling information technology-enabled processes using pattern recognition methodology. The methodology gives a lot of flexibility to managers to monitor multiple processes collectively and avoids the manual plotting and interpretation of control charts.

Originality/value

The application of control chart pattern recognition methodology for monitoring service industry processes are rare. This is an application of the methodology for controlling information technology-enabled processes. This study also demonstrates the usefulness of deep learning techniques for process control.
Prioritisation of root cause analysis in production disturbance management
Authors: Soares Ito Adriana , Ylipää Torbjörn , Gullander Per , Bokrantz Jon , Skoogh Anders
Published: June 2021

Purpose

Manufacturing companies struggle to manage production disturbances. One step of such management deals with prioritising those disturbances which should undergo root cause analysis. The focus of this work is on two areas. First, investigating current challenges faced by manufacturing companies when prioritising root cause analysis of production disturbances. Second, identifying the stakeholders and factors impacted by production disturbances. Understanding the current challenges and identifying impacted stakeholders and factors allows the development of more efficient prioritisation strategies and, thus, contributes to the reduction of frequency and impact of disturbances.

Design/methodology/approach

To achieve the intended purpose of this research, a qualitative approach was chosen. A series of interviews was conducted with practitioners, to identify current challenges. A series of focus groups was also held, to identify the impacted stakeholders and factors by disturbances.

Findings

Various challenges were identified. These are faced by manufacturing companies in their prioritisation of production disturbances and relate to the time needed, criteria used, centralisation of the process, perspective considered and data support. It was also found that a wide range of stakeholders is impacted by production disturbances, surpassing the limits of production and maintenance departments. Furthermore, the most critical factors impacted are quality, work environment, safety, time, company results, customer satisfaction, productivity, deliverability, resource utilisation, profit, process flow, plannability, machine health and reputation.

Originality/value

The current situation regarding root cause analysis prioritisation has not been identified in previous works. Moreover, there has been no prior systematic identification of the various stakeholders and factors impacted by production disturbances.
Developing a maintenance-focussed conservation model: an Australian overview
Authors: Cruz Arturo , Coffey Vaughan , Chan Tommy H.T. , Perovic Miljenka
Published: June 2021

Purpose

This paper presents a conceptual design process for developing a maintenance-focused heritage conservation model. Currently, there are several intervention approaches that can be applied in conservation from reconstruction, restoration and repairs to a “do-nothing” approach. This paper examines whether a maintenance solution is more than just an option or a necessity. The aim of the paper is to study the challenges and opportunities when putting more emphasis on the maintenance approach in conservation.

Design/methodology/approach

This research was conducted in an Australian context, where many major buildings were constructed from the 19th and 20th centuries and are now categorised as “modern heritage”. three case studies were undertaken to inform this paper and others. In addition, 17 global heritage conservation experts were interviewed, and their responses were analysed. Also, comparative field observations and archival records were examined and used to develop the initial framework model. Finally, using focus group discussions amongst 7 experts, the framework was reviewed and formally validated in order to ensure the development of a useful model for use in devising an effective maintenance management plan and monitoring conditions in heritage buildings.

Findings

This paper supports others in a series that have already been accepted by this journal, focussing the research on heritage building conservation being conducted in Australia, the homeland of the Burra Charter. The other papers are entitled (1) model for the maintenance-focused heritage building conservation and (2) engineering in heritage conservation.

Originality/value

The paper examines contemporary issues in heritage building maintenance and conservation in Australia and focusses specifically on the lack of focus on maintenance as a conservation intervention for heritage buildings.
Health information-seeking behavior in the time of COVID-19: information horizons methodology to decipher source path during a global pandemic
Authors: Zimmerman Margaret S.
Published: June 2021

Purpose

To determine the differences, as represented by information horizons mapping, in the health information-seeking behavior from a group of participants between March 2019 and April 2020 of the novel coronavirus pandemic.

Design/methodology/approach

In March 2019, the author conducted a study on health information-seeking behavior in which 149 participants drew information horizons maps in a health-related context. They also took health and information literacy assessments. This exact study was replicated using the same population in April 2020 to determine the differences in what the participants drew on their maps and how these changes interacted with their health and information literacy, their age and their education.

Findings

There is a statistically significant difference in the increased number of sources and the ranked quality of the sources that people used during the pandemic. Participants were much more likely to use credible sources and news sources, especially if they were older, more educated and had higher literacy levels – both health and information. They also relied heavily on social media. The participant group in the pandemic had a much heavier reliance on sources that are often used in a passive encountering way but engaging with them in an active information-seeking manner. The health information-seeking behavior in this study did not adhere to other research that found issue with information overload, avoidance and cyberchondria in response to crisis situations.

Originality/value

This article utilizes information horizons methodology to explore pre- and post-pandemic information-seeking. It is completely unique in this approach.
“Data stickiness” in interagency government data sharing: a case study
Authors: Zhou Lihong , Chen Longqi , Han Yingying
Published: June 2021

Purpose

The provision of high-quality e-Government services requires efficient and collaborative sharing of data across varied types of government agencies. However, interagency government data sharing (IDS) is not always spontaneous, active and unconditional. Adopting a stickiness theory, this paper reports on a research study, which explores the causes of data stickiness in IDS.

Design/methodology/approach

This study employed an inductive case study approach. Twenty-three officials from the government of City M in Hubei Province, Central China, were approached and interviewed using a semi-structured question script.

Findings

The analysis of the interview data pointed to 27 causes of data stickiness in five main themes: data sharing willingness; data sharing ability; data articulatability; data residence; and data absorptive capacity. The analysis revealed that interagency tensions and lack of preparedness of individual agencies are the main causes of data stickiness in IDS.

Originality/value

The case setting is based on China's Government, but the findings offer useful insights and indications that can be shared across international borders.
Potential COVID-19 impacts on the transition to Industry 4.0 in the Brazilian manufacturing sector
Authors: Cazeri Gustavo Tietz , Anholon Rosley , Santa-Eulalia Luis Antonio , Rampasso Izabela Simon
Published: June 2021

Purpose

The purpose of this viewpoint is to present some reflections about the coronavirus disease 2019 (COVID-19) pandemic impacts on the transition to Industry 4.0 in the Brazilian manufacturing sector context.

Design/methodology/approach

Initially, a bibliographic research study was carried out to establish a theoretical background and contextualization. After analysing different kinds of documents, the authors of this viewpoint discussed potential COVID-19 impacts on the transition to Industry 4.0 in the Brazilian manufacturing sector. A multidisciplinary discursive approach was used in the debates.

Findings

The COVID-19 pandemic will negatively influence the transition of Brazilian manufacturing sector to Industry 4.0. Despite the fact that some “World Class Companies” based in Brazil still continue the transition process towards the “Digital Revolution”, most of Brazilian manufacturing companies are postponing important initiatives related to Industry 4.0 due to uncertainties. In addition, policies promoting innovation are increasingly necessary.

Practical implications

This viewpoint presents interesting implications for researchers and society. Researchers can use these reflections to structure surveys or case studies to better understand the aforementioned impacts on companies due to the pandemic. These reflections can also be used by society for public policy debates. For companies, the information presented highlights the relevance of Industry 4.0 as an important phenomenon to manufacturing sector and companies' competitiveness.

Originality/value

This viewpoint presents reflections which may be used to encourage debates about how to manage digital transformation in the manufacturing sector during an unstable environment.
Linking coopetition benefits and innovative performance within small and medium-sized enterprises networks: a strategic approach on knowledge sharing and direct collaboration
Authors: Vătămănescu Elena-Mădălina , Mitan Andreea , Andrei Andreia Gabriela , Ghigiu Alexandru Mihai
Published: June 2021

Purpose

The present study aims to tackle SMEs (small and medium-sized enterprises) managers' awareness of coopetition benefits underpinning the process of knowledge sharing with a view to achieve innovative performance. The scrutiny of coopetition is placed within the context of SMEs strategic networks, which foster a fertile ground for competitive knowledge sharing and direct collaboration among members.

Design/methodology/approach

In total, 102 top managers and business owners of European steel SMEs were questioned regarding various issues related to coopetition, knowledge, collaboration and innovative performance strategies. The collected data were analyzed via the technique of partial least squares structural equation modeling (PLS-SEM).

Findings

The obtained values confirm that intense competition in the field stimulates SMEs to become aware of the benefits of coopetition. This awareness directly influences the innovative performance of the SMEs, as well as their interest in competitive knowledge sharing and their willingness to engage in direct collaboration. Direct collaboration catalyzes more intense competitive knowledge sharing at the inter-unit level whereas both direct collaboration and competitive knowledge sharing lead to better innovative performance in the case of the studied steel SMEs.

Research limitations/implications

A key theoretical contribution resides in revealing the influence of manifold factors in the overall equation of innovative performance, integrating competition, coopetition and knowledge sharing as antecedents.

Originality/value

The research advances a phenomenological view on SMEs networks in their strategy to leverage competitive knowledge and enhance system-driven innovation.
Do governmental, technological and organizational factors influence the performance of financial management systems?
Authors: Chen Yu , Hao Shengbin , Li A.
Published: June 2021

Purpose

The critical issue in financial management is investigating the role of government in an organization's economy. Governmental facilities, loans and long-term financial plans may affect the performance of financial management systems. Financial management systems may be affected by various other factors, such as organizational, technological and governmental factors. Studying and investigating the influence of organizational, technological and governmental factors on financial management systems' performance is the primary goal of this paper.

Design/methodology/approach

Financial management has always been affected by the increasing role of technology. Also, the use of financial software, the entry of computer-based computing and math planning are examples of technology entry to financial management that has led to changes in recent years. Data were collected from the insurance offices through a questionnaire. Distributed questionnaires were conducted on a Likert scale. The causal model has been appraised by the structural equation modeling (SEM) method that has been utilized to assess the validity and reliability of the model. The software has been used to evaluate the questionnaire, and the hypotheses of the research are evaluated using SPSS 22 and SMART-PLS software.

Findings

The results showed that organizational, technological and governmental factors directly affect financial management systems' performance. For this reason, the role of organizational, technological and governmental factors on the success of financial management systems in insurance companies must be considered for decision-making in the future.

Research limitations/implications

This study includes some restrictions required to be examined in assessing the outcomes. First, sample research was selected from the managers of the insurance offices in Harbin, China. So, the sample size is not big, and the generalization of the results is limited. Second, the current research might have ignored other variables, which affect the performance of financial management systems. Future researchers intend to investigate the impact of investments and projects on financial management systems' performance as a proposal. Nevertheless, the subsequent investigation can assess vital factors like investments and plans on financial management systems' performance.

Practical implications

The research also includes insurance companies and all departments and individuals associated with financial management systems somehow.

Originality/value

In the current article, the performance of financial management systems is highlighted, and the method to resolve the issue has been utilized as an experimental example. This article's introduced model supplies a comprehensive framework to investigate the impact of organizational, technological and governmental factors on financial management systems' performance.
Influence of reduced diffusing capacity and FEV1on outcome after cardiac surgery
Authors: Risom Emilie C. , Buggeskov Katrine B. , Petersen René H. , Mortensen Jann , Ravn Hanne B.
Published: June 2021

Background

Impaired lung function is a well‐known risk factor in cardiac surgery patients and reduced forced expiratory volume in 1 second (FEV1) is associated with increased mortality. However, there is limited knowledge regarding the influence of impaired diffusing capacity of the lungs for carbon monoxide (DLCO) in unselected cardiac surgery patients. The aim of this study was to investigate the association of impaired DLCO and/or reduced FEV1on post‐operative mortality and morbidity in cardiac surgery patients.

Methods

In a prospective cohort study, 390 patients scheduled for elective cardiac surgery underwent preoperative lung function test including spirometry and DLCO measurements. We defined reduced FEV1as FEV1below lower limit of normal (LLN) and impaired DLCO as DLCO <60% of predicted.

Results

Mortality within 1 year (90‐570 days) was significantly higher in patients with impaired DLCO (12% vs 3%,P = .010) and with reduced FEV1(9% vs 3%,P = .028). Mortality was higher in patients with impaired DLCO both in the presence and absence of FEV1 < LLN. In multivariate analysis, only impaired DLCO [OR: 3.3, 95% confidence interval (CI) 1.4‐7.5;P = .005] and age (OR: 1.1 per year, 95% CI 1.0‐1.2;P = .001) were independent predictors of the combined outcome of mortality and prolonged intensive care unit (ICU) stay. Impaired DLCO was also associated with post‐operative respiratory complications.

Conclusion

In patients undergoing elective cardiac surgery, preoperative impaired FEV1and DLCO were associated with increased mortality and morbidity. In multivariate analysis, only DLCO and age were independent predictors of a combined outcome of mortality and prolonged ICU stay.
Human muscle stem cells are refractory to aging
Authors: Novak James S. , Mázala Davi A. G. , Nearing Marie , Hindupur Ravi , Uapinyoying Prech , Habib Nayab F. , Dickson Tessa , Ioffe Olga B. , Harris Brent T. , Fidelia‐Lambert Marie N. , Rossi Christopher T. , Hill D. Ashely , Wagner Kathryn R. , Hoffman Eric P. , Partridge Terence A.
Published: June 2021

Age‐related loss of muscle mass and strength is widely attributed to limitation in the capacity of muscle resident satellite cells to perform their myogenic function. This idea contains two notions that have not been comprehensively evaluated by experiment. First, it entails the idea that we damage and lose substantial amounts of muscle in the course of our normal daily activities. Second, it suggests that mechanisms of muscle repair are in some way exhausted, thus limiting muscle regeneration. A third potential option is that the aged environment becomes inimical to the conduct of muscle regeneration. In the present study, we used our established model of human muscle xenografting to test whether muscle samples taken from cadavers, of a range of ages, maintained their myogenic potential after being transplanted into immunodeficient mice. We find no measurable difference in regeneration across the range of ages investigated up to 78 years of age. Moreover, we report that satellite cells maintained their myogenic capacity even when muscles were grafted 11 days postmortem in our model. We conclude that the loss of muscle mass with increasing age is not attributable to any intrinsic loss of myogenicity and is most likely a reflection of progressive and detrimental changes in the muscle microenvironment such as to disfavor the myogenic function of these cells.
Dual trajectories of cannabis and alcohol use among young adults in a state with legal nonmedical cannabis
Authors: Guttmannova Katarina , Fleming Charles B. , Rhew Isaac C. , Alisa Abdallah Devon , Patrick Megan E. , Duckworth Jennifer C. , Lee Christine M.
Published: June 2021

Background

Understanding the nature of the association between cannabis and alcohol use within individuals over time in the era of legalized cannabis is of crucial importance for assessing the public health consequences of increasing cannabis use. An important unanswered question is whether cannabis and alcohol use substitute for one another. Specifically, is greater use of one substance associated with less use of the other substance (i.e., a negative association) or are the substances complementary and their association positive?

Methods

We used 24 consecutive months of data on a young adult sample (n = 774; 56% female, age 18–25 during the study) who drank alcohol in the year prior to enrollment. The sample was recruited in Washington State in 2015/2016 (after legalization of nonmedical cannabis) using media advertisements and community flyers and outreach. Using parallel process latent growth curve models, we assessed three types of association between cannabis and alcohol use across the 24‐month period: (1) an association between average levels of cannabis and alcohol use; (2) an association between rates of change in cannabis and alcohol use; and (3) correlations between shorter‐term deviations/fluctuations off of longer‐term trajectories of level and change in cannabis and alcohol use.

Results

We found a positive association between the average frequency of cannabis and alcohol use; individuals who used cannabis more frequently on average also drank alcohol more frequently on average. Change over time in cannabis use was positively associated with change in alcohol use. There was also a contemporaneous positive association between fluctuations in cannabis and alcohol use.

Conclusions

Overall, we found no evidence of substitution. Rather, the results suggest a complementary relationship between cannabis and alcohol use, such that the use of cannabis and alcohol rises and falls together.
Institutional trading in stock market anomalies in Australia
Authors: Zhong Angel
Published: June 2021

This study examines the role played by institutional investors in Australia. With a unique database that provides comprehensive coverage of institutional ownership, this study is the first to examine the overall performance of all institutions in the Australian equity market. Institutional investors do not outperform the market. Examining their trading activities in greater detail, we find that institutional investors do not exploit well‐known stock market anomalies, with the exception of momentum. Institutional investors are also found to sell loser stocks heavily at the end of the financial year, thus contributing to a strong quarter‐end momentum effect.
Historical trends for the standards in scrotal ultrasonography: What was, what is and what will be normal
Authors: Lotti Francesco , Bertolotto Michele , Maggi Mario
Published: June 2021

Background

Ultrasonography is the gold standard imaging method for scrotal investigation. Colour Doppler ultrasonography, contrast‐enhanced ultrasonography and sonoelastography allow sonographers to assess size, echotexture, vascular features and stiffness of the scrotal organs and abnormalities. Scrotal ultrasonography has been used to investigate male reproductive health, scrotal pain, masses and trauma. However, ultrasonography thresholds/classifications used to distinguish normal and pathologic features of the scrotal organs have changed over time, and have not yet been fully standardized.

Objectives

To evaluate historical trends for the standards in scrotal ultrasonography: what was, what is and what will be normal.

Methods

An extensive Medline search was performed identifying the most relevant studies in the English language from inception to date.

Results

We provide here (i) a brief overview of the history of ultrasonography, (ii) current indications for scrotal ultrasonography and (iii) previous and current normal values, cut‐offs and classifications of the main colour‐Doppler ultrasonography parameters/characteristics of the scrotal organs, as derived from recent guidelines and evidence‐based studies. In addition, we report recommendations and the clinical utility of contrast‐enhanced ultrasonography and sonoelastography. Finally, we discuss critical issues needing further evidence and future directions to fill in the current gaps.

Discussion

Several studies on scrotal ultrasonography are available. However, guidelines/recommendations dealing with specific ultrasonography applications have been published only in recent years. More recently, the European Academy of Andrology published evidence‐based scrotal colour‐Doppler ultrasonography reference ranges/normative parameters derived from a cohort of healthy, fertile men. In addition, a standardization of the methodology to evaluate qualitative and quantitative colour‐Doppler ultrasonography parameters was reported. Other international societies reported indications, methodological standards, clinical utility and limitations of contrast‐enhanced ultrasonography and sonoelastography.

Conclusions

To date, colour‐Doppler ultrasonography normative values for the scrotal organs are available. However, a wide international consensus on assessment and classification of several ultrasonography parameters is still lacking. An alignment of the world societies on these issues is advocated.
Intestinal mesenchymal cells regulate immune responses and promote epithelial regeneration in vitro and in dextran sulfate sodium‐induced experimental colitis in mice
Authors: Hidalgo‐Garcia Laura , Molina‐Tijeras José Alberto , Huertas‐Peña Francisco , Ruiz‐Malagón Antonio Jesús , Diez‐Echave Patricia , Vezza Teresa , Rodríguez‐Sojo María Jesús , Morón Rocío , Becerra‐Massare Patricia , Rodríguez‐Nogales Alba , Gálvez Julio , Rodríguez‐Cabezas María Elena , Anderson Per
Published: June 2021

Aim

Disruption of the intestinal mucosal tolerance, that is, the immunological unresponsiveness to innocuous food antigens and the commensal microbiota, in the colon is associated with several chronic diseases including inflammatory bowel disease (IBD). Understanding the mechanisms responsible for intestinal mucosal tolerance has potential translational value for its therapy and management. Human intestinal mesenchymal cells (iMCs) play important roles in colonic mucosal tolerance, but further studies on their tissue regenerative and immunomodulatory capacities are necessary in order to fully understand their function in health and disease.

Methods

In this study, we have isolated and analysed the capacity of human iMCs to promote wound healing and modulate immune responses in vitro and in vivo, using the dextran sulfate sodium (DSS)‐induced colitis model.

Results

Cultured iMCs were CD45−CD73+CD90+CD105+ and accelerated the wound closure in a normal colon mucosa (NCM) 356 human epithelial cell wound healing assay. Furthermore, iMCs blocked the LPS‐mediated induction of TNF‐α in THP‐1 macrophages and inhibited the proliferation of peripheral blood mononuclear cells, partly through the induction of indoleamine‐2,3‐dioxygenase. In DSS colitic mice, iMCs administration reduced the disease activity index and ameliorated intestinal tissue damage and permeability. Furthermore, iMCs reduced intestinal inflammation, evidenced by a decreased mRNA expression of pro‐inflammatory cytokines, reduced IL‐1β secretion by intestinal explants and inhibited colonic iNOS protein expression.

Conclusions

Our data show that human iMCs isolated from the noninflamed intestine possess tissue‐regenerative and immunomodulatory capacities that could potentially be harnessed/restored in order to reduce IBD severity.
High‐intensity exercise in hypoxia improves endothelial function via increased nitric oxide bioavailability in C57BL/6 mice
Authors: Lavier Jessica , Beaumann Manon , Menétrey Steeve , Bouzourène Karima , Rosenblatt‐Velin Nathalie , Pialoux Vincent , Mazzolai Lucia , Peyter Anne‐Christine , Pellegrin Maxime , Millet Grégoire P.
Published: June 2021

Aim

The optimal exercise intensity to improve endothelial function remains unclear, as well as whether the addition of hypoxia could potentiate this function. Therefore, the aim of this study was to compare the effects of different exercise intensities in normoxia and hypoxia on vascular reactivity and nitric oxide (NO) bioavailability in mice.

Methods

C57BL/6 mice underwent treadmill running three times per week, for 4 weeks at either low, maximal or supramaximal intensity in normoxia or hypoxia (inspire oxygen fraction = 0.13). Vascular reactivity and expression of genes and proteins involved in NO production/bioavailability were assessed in aorta using isolated vessel tension experiments, RT‐qPCR and western blot, respectively. Circulating NO metabolites and pro‐/antioxidant markers were measured.

Results

Hypoxic exercise improved both acetylcholine‐induced vasorelaxation and phenylephrine‐induced vasoconstriction compared to normoxic exercise, independently of intensity. In hypoxia, a higher acetylcholine‐induced vasorelaxation was observed with high intensities (supramaximal and maximal) compared to low intensity. Exercise protocols modulated endothelial nitric oxide synthase (eNOS) and α1‐adrenergic receptor (α1‐AR) mRNA level, but not superoxide dismutase 3 (SOD3) and p47phox. No significant differences were observed for protein expression of α1‐AR, total eNOS, phosphorylated eNOS, SOD isoforms and p47phox. However, plasma SOD and catalase activities were significantly increased in hypoxic supramaximal compared to hypoxic low intensity, while concentration of nitrotyrosine significantly decreased. The latter was also observed in hypoxic maximal and supramaximal compared to the same intensities in normoxia.

Conclusion

Hypoxic high‐intensity exercise increases NO bioavailability and improves vascular function, opening promising clinical perspectives for cardiovascular disease prevention.
Reliable kidney size determination by magnetic resonance imaging in pathophysiological settings
Authors: Gladytz Thomas , Millward Jason M. , Cantow Kathleen , Hummel Luis , Zhao Kaixuan , Flemming Bert , Periquito Joāo S. , Pohlmann Andreas , Waiczies Sonia , Seeliger Erdmann , Niendorf Thoralf
Published: June 2021

Aim

Kidney diseases constitute a major health challenge, which requires noninvasive imaging to complement conventional approaches to diagnosis and monitoring. Several renal pathologies are associated with changes in kidney size, offering an opportunity for magnetic resonance imaging (MRI) biomarkers of disease. This work uses dynamic MRI and an automated bean‐shaped model (ABSM) for longitudinal quantification of pathophysiologically relevant changes in kidney size.

Methods

A geometry‐based ABSM was developed for kidney size measurements in rats using parametric MRI (T2, T2* mapping). The ABSM approach was applied to longitudinal renal size quantification using occlusion of the (a) suprarenal aorta or (b) the renal vein, (c) increase in renal pelvis and intratubular pressure and (d) injection of an X‐ray contrast medium into the thoracic aorta to induce pathophysiologically relevant changes in kidney size.

Results

The ABSM yielded renal size measurements with accuracy and precision equivalent to the manual segmentation, with >70‐fold time savings. The automated method could detect a ~7% reduction (aortic occlusion) and a ~5%, a ~2% and a ~6% increase in kidney size (venous occlusion, pelvis and intratubular pressure increase and injection of X‐ray contrast medium, respectively). These measurements were not affected by reduced image quality following administration of ferumoxytol.

Conclusion

Dynamic MRI in conjunction with renal segmentation using an ABSM supports longitudinal quantification of changes in kidney size in pathophysiologically relevant experimental setups mimicking realistic clinical scenarios. This can potentially be instrumental for developing MRI‐based diagnostic tools for various kidney disorders and for gaining new insight into mechanisms of renal pathophysiology.
A drug screen with approved compounds identifies amlexanox as a novel Wnt/β‐catenin activator inducing lung epithelial organoid formation
Authors: Costa Rita , Wagner Darcy E. , Doryab Ali , De Santis Martina M. , Schorpp Kenji , Rothenaigner Ina , Lehmann Mareike , Baarsma Hoeke A. , Liu Xueping , Schmid Otmar , Campillos Monica , Yildirim Ali Önder , Hadian Kamyar , Königshoff Melanie
Published: June 2021

Background and Purpose

Emphysema is an incurable disease characterized by loss of lung tissue leading to impaired gas exchange. Wnt/β‐catenin signalling is reduced in emphysema, and exogenous activation of the pathway in experimental models in vivo and in human ex vivo lung tissue improves lung function and structure. We sought to identify a pharmaceutical able to activate Wnt/β‐catenin signalling and assess its potential to activate lung epithelial cells and repair.

Experimental Approach

We screened 1216 human‐approved compounds for Wnt/β‐catenin signalling activation using luciferase reporter cells and selected candidates based on their computationally predicted protein targets. We further performed confirmatory luciferase reporter and metabolic activity assays. Finally, we studied the regenerative potential in murine adult epithelial cell‐derived lung organoids and in vivo using a murine elastase‐induced emphysema model.

Key Results

The primary screen identified 16 compounds that significantly induced Wnt/β‐catenin‐dependent luciferase activity. Selected compounds activated Wnt/β‐catenin signalling without inducing cell toxicity or proliferation. Two compounds were able to promote organoid formation, which was reversed by pharmacological Wnt/β‐catenin inhibition, confirming the Wnt/β‐catenin‐dependent mechanism of action. Amlexanox was used for in vivo evaluation, and preventive treatment resulted in improved lung function and structure in emphysematous mouse lungs. Moreover, gene expression of Hgf, an important alveolar repair marker, was increased, whereas disease marker Eln was decreased, indicating that amlexanox induces pro‐regenerative signalling in emphysema.

Conclusion and Implications

Using a drug screen based on Wnt/β‐catenin activity, organoid assays and a murine emphysema model, amlexanox was identified as a novel potential therapeutic agent for emphysema.