bluuebunny/crossref_metadata_2025_split huggingface dataset:
Localization of PPM1H phosphatase tunes Parkinson’s disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis
Authors: Yeshaw Wondwossen M. , Adhikari Ayan , Chiang Claire Y. , Dhekne Herschel S. , Wawro Paulina S. , Pfeffer Suzanne R. 
Published: June 2023

ABSTRACTPPM1H phosphatase reverses Parkinson’s disease-associated, LRRK2-mediated Rab GTPase phosphorylation. We show here that PPM1H relies on an N-terminal amphipathic helix for Golgi localization. The amphipathic helix enables PPM1H to bind to liposomes in vitro, and small, highly curved liposomes stimulate PPM1H activity. We artificially anchored PPM1H to the Golgi, mitochondria, or mother centriole. Our data show that regulation of Rab10 GTPase phosphorylation requires PPM1H access to Rab10 at or near the mother centriole. Moreover, poor co-localization of Rab12 explains in part why it is a poor substrate for PPM1H in cells but not in vitro. These data support a model in which localization drives PPM1H substrate selection and centriolar PPM1H is critical for regulation of Rab GTPase-regulated ciliogenesis. Moreover, Golgi localized PPM1H maintains active Rab GTPases on the Golgi to carry out their non-ciliogenesis-related functions in membrane trafficking.Significance StatementPathogenic, hyperactive LRRK2 kinase is strongly linked to Parkinson’s disease and LRRK2 phosphorylates a subset of Rab GTPases that are master regulators of membrane trafficking. PPM1H phosphatase specifically dephosphorylates Rab8A and Rab10, the major LRRK2 substrates. Here we provide novel cell biological and biochemical insight related to the localization and activation of PPM1H phosphatase. Understanding how PPM1H modulates LRRK2 activity is of fundamental interest and also important, as activators of PPM1H may eventually benefit Parkinson’s disease patients.
A novel 4D fMRI clustering technique to examine event-related spatiotemporal dynamics of face processing in naturalistic stimuli
Authors: Ekstrand C. 
Published: June 2023

AbstractCortical function is complex, nuanced, and involves information processing in a multimodal and dynamic world. However, previous functional magnetic resonance imaging (fMRI) research has generally characterized static activation differences between strictly controlled proxies of real-world stimuli that do not encapsulate the complexity of everyday multimodal experiences. Of primary importance to the field of neuroimaging is the development of techniques that distill complex spatiotemporal information into simple, behaviorally relevant representations of neural activation. Herein, we present a novel 4D spatiotemporal clustering method to examine dynamic neural activity associated with events (specifically the onset of human faces in audiovisual movies). Results from this study showed that 4D spatiotemporal clustering can extract clusters of fMRI activation over time that closely resemble the known spatiotemporal pattern of human face processing without the need to model a hemodynamic response function. Overall, this technique provides a new and exciting window into dynamic functional processing across both space and time using fMRI that has wide applications across the field of neuroscience.
Secondary structures that regulate mRNA translation provide insights for ASO-mediated modulation of cardiac hypertrophy
Authors: Hedaya Omar M. , Subbaiah Kadiam C. Venkata , Jiang Feng , Xie Li Huitong , Wu Jiangbin , Khor EngSoon , Zhu Mingyi , Mathews David H. , Proschel Chris , Yao Peng 
Published: June 2023

AbstractTranslation of upstream open reading frames (uORFs) typically abrogates translation of main (m)ORFs. The molecular mechanism of uORF regulation in cells is not well understood. Here, we identified a double-stranded RNA (dsRNA) structure residing within theGATA4uORF that augments uORF translation and inhibits mORF translation. Antisense oligonucleotides (ASOs) that disrupt this dsRNA structure promote mORF translation, while ASOs that base-pair immediately downstream (i.e., forming a bimolecular double-stranded region) of either the uORF or mORF start codon enhance uORF or mORF translation, respectively. Human cardiomyocytes and mice treated with a uORF-enhancing ASO showed reduced cardiac GATA4 protein levels and increased resistance to cardiomyocyte hypertrophy. We further show the general utility of uORF-dsRNA- or mORF- targeting ASO to regulate mORF translation for other mRNAs. Our work demonstrates a regulatory paradigm that controls translational efficiency and a useful strategy to alter protein expression and cellular phenotypes by targeting or generating dsRNA downstream of a uORF or mORF start codon.Bullet points for discoveriesdsRNA withinGATA4uORF activates uORF translation and inhibits mORF translation.ASOs that target the dsRNA can either inhibit or enhanceGATA4mORF translation.ASOs can be used to impede hypertrophy in human cardiomyocytes and mouse hearts.uORF- and mORF-targeting ASOs can be used to control translation of multiple mRNAs.
Assumptions for creating matrices of evidence to estimate overlap of primary studies in overviews of reviews: Protocol for a meta-research study
Authors: Bracchiglione Javier , Meza Nicolás , Lunny Carole , Pieper Dawid , Madrid Eva , Urrútia Gerard , Bonfill Cosp Xavier 
Published: June 2023

AbstractIntroductionOverlap of primary studies among systematic reviews (SRs) included in an overview is a major challenge, as it may bias results or artificially increase the precision of the synthesis. Matrices of evidence and corrected covered area (CCA) calculation are recommended methods to manage overlap, but there is little guidance on how to construct these matrices. This research aims to explore variations in the estimation of overlap using CCA matrices under different assumptions.MethodsWe will include overviews published in 2023. We will describe the methods used by authors to deal with overlap, and we will calculate a summary CCA (a CCA for the whole matrix of evidence) and a pairwise CCA (a CCA for each possible pair of included SRs), comparing the results under different assumptions that may modify the evidence matrix and thus the CCA. These assumptions include: publication-thread adjustments (i.e. the consideration of each set of references regarding a single primary study as a unique row in a matrix of evidence), scope adjustments (i.e. the consideration only of the SRs and primary studies providing useful data for a given outcome within an overview) and chronological structural missingness adjustments (i.e. the exclusion of primary studies published after a given SR for purposes of CCA calculation). We will assess overlap at an overview and outcome level.DiscussionWe propose clear definitions for the key assumptions for creating matrices of evidence. We expect to provide a guide for overview authors to better interpret their CCA estimations.Article SummaryStrengths and limitations of this studyThis protocol explores the assumptions underlying the overlap assessment in overviews of systematic reviews, that so far have not been explicitly addressed.These assumptions include scope adjustments, publication-thread adjustments, structural missingness adjustments, and analysis at an overview or outcome level.We provide clear definitions for key overlap concepts that will guide authors for making their overlap assessments more explicit when using a matrix of evidence or corrected covered area approach.We plan to conduct exploratory analyses under different assumptions in a purposive sample of overview, hence, we will not comprehensively include all the overviews in the study period.We will conduct all the analysis calculating the corrected covered area for the whole matrices (overall approach) and for every possible pair of systematic reviews within each matrix (pairwise approach).
A small molecule inhibitor of PTP1B and PTPN2 enhances T cell anti-tumor immunity
Authors: Liang Shuwei , Tran Eric , Du Xin , Dong Jiajun , Sudholz Harrison , Chen Hao , Qu Zihan , Huntington Nicholas D. , Babon Jeffrey J. , Kershaw Nadia J. , Zhang Zhong-Yin , Baell Jonathan B. , Wiede Florian , Tiganis Tony 
Published: June 2023

ABSTRACTThe inhibition of protein tyrosine phosphatases 1B (PTP1B) and N2 (PTPN2) has emerged as an exciting approach for bolstering T cell anti-tumor immunity. ABBV-CLS-484 is a PTP1B/PTPN2 inhibitor in clinical trials for solid tumors. Here we have explored the therapeutic potential of a related small-molecule-inhibitor, Compound-182. We demonstrate that Compound-182 is a highly potent and selective active site competitive inhibitor of PTP1B and PTPN2 that enhances T cell recruitment and activation and represses the growth of tumors in mice, without promoting overt immune-related toxicities. The enhanced anti-tumor immunity in immunogenic tumors could be ascribed to the inhibition of PTP1B/PTPN2 in T cells, whereas in cold tumors, Compound-182 elicited direct effects on both tumor cells and T cells. Importantly, treatment with Compound-182 rendered otherwise resistant tumors sensitive to α-PD1 therapy. Our findings establish the potential for small molecule inhibitors of PTP1B and PTPN2 to enhance anti-tumor immunity and combat cancer.
Global brands or local heroes? A comparative study of Egyptian consumer perceptions and behaviors in the fashion and apparel industry
Authors: Boseila Iman , Mahrous Abeer A. , Abouaish Ehab 
Published: June 2023

PurposeThe paper examined the impact of brand-identity expressiveness and perceived brand value that was neglected in prior literature, in addition to perceived brand quality and prestige, on behavioral intention. Research also tests if certain consumer values moderate this relationship.Design/methodology/approachMall-interception technique was used. Also, partial least square-structural equation modelling (PLS-SEM) was used to analyze data and test research hypotheses.FindingsResults indicate that perceived brand globalness (PBG) and perceived brand localness (PBL) are significantly positively associated with perceived quality and prestige. Besides, the inclusion of brand-identity expressiveness and perceived brand value was supported. PBL showed a greater association with brand identity expressiveness compared to PBG, different from previous findings. Furthermore, the total indirect effect of PBG on behavioral intentions was significant through the routes of perceived quality and prestige, compared to a weak and non-significant effect for PBL through the quality route.Originality/valueThis study proposes a comprehensive model testing additional pathways through which global and local brands can boost their preferences.
Developing a multidimensional performance measurement framework for international construction joint ventures (ICJVs): the perspective of Ghana-hosted ICJVs' practitioners
Authors: Tetteh Mershack Opoku , Chan Albert P.C. , Darko Amos , Özorhon Beliz , Adinyira Emmanuel 
Published: June 2023

PurposeInternational construction joint ventures (ICJVs) will fully realize their potential for success and effectively monitor performance when an adequate and suitable performance benchmark is established. However, existing studies fall short of adequately providing a mutually acceptable benchmark for assessing the performance of ICJVs. This study aims to develop an adequate and suitable performance measurement framework for ICJVs.Design/methodology/approachA twofold structured questionnaire survey, supplemented by semi-structured interviews, was used to collect data from the practitioners of ICJVs hosted in the developing country of Ghana. The data were analyzed by using descriptive statistics, confirmatory factor analysis (CFA) and a hybrid-fuzzy logic approach.FindingsA list of 30 performance indicators (PIs), defined by project performance, perceived satisfaction, company/partner performance, socio-environmental performance and performance of ICJV management, was validated and proved to be significant. Only 22 out of the 30 PIs, focusing on project efficiency, societal improvement and organizational goals are realized by the ICJV practitioners. Further, suitable determinants and viable quantitative ranges for measuring each PI are established to prevent different interpretations of the meanings of PIs and objectively express the level of success in quantitative terms. The results call for further investigation of the convergence between the practice of and research into some PIs (e.g. socio-environmental performance) and a range of different performance levels (PLs) in a more scientific manner.Practical implicationsThis study not only advances the knowledge base and practice of performance measurement in ICJVs but could also assist stakeholders and decision-makers to assess, compare and monitor the performance of different ICJV projects on common grounds objectively.Originality/valueThis study not only comprehensively assessed PIs – what to measure – but also systematically determined suitable determinants – how to measure – for each PI.
The long-run impact of remittances on house prices in Kenya
Authors: Chege Fredrick , Gholipour Hassan F. , Yam Sharon 
Published: June 2023

Purpose
Given the coincidental and sustained rise in house prices and foreign capital flows in Kenya, this study aims to understand whether a long-run relationship exists between real diaspora remittances and real house prices.

Design/methodology/approach
This study uses data from 2004-Q1 to 2020-Q4 and applies an autoregressive distributed lag model for estimation.

Findings
The results indicate that a positive and significant relationship exists between real remittances and real house prices in Kenya in the long run.

Originality/value
To the best of the authors’ knowledge, there is no study exploring the relationship between real remittance inflows and house prices in Kenya, after controlling for other key macroeconomic determinants of house prices. This study addresses this research gap.
Does urban tourism development impact urban housing prices?
Authors: Cong Shufeng , Chin Lee , Abdul Samad Abdul Rahim 
Published: June 2023

Purpose
The purpose of this study is to investigate the relationship between tourism development and urban housing prices in Chinese cities. Specifically, the study aimed to explore whether there is a relationship between the two variables in tourist and non-tourist cities and whether there is a non-linear relationship between them.

Design/methodology/approach
In this study, the entropy method was used to construct the China City Tourism Development Index, which provides a more comprehensive measure of the level of tourism development in different cities. In total, 45 major cities in China were studied using the panel data approach for the period of 2011 to 2019.

Findings
The empirical analysis conducted for this study found that tourism development affects urban house prices, and that there is an inverted U-shaped relationship. However, this varies across cities, with house prices in tourist cities tending to be more influenced by tourism development than non-tourist cities. Also, foreign direct investment, population size, fixed asset investment and disposable income per capita were found to have an impact on house prices in both tourism and non-tourism cities.

Originality/value
There are significant differences in tourism development and urban house prices in different cities in China. This study considers these differences when examining the impact of tourism on house prices in 45 major cities in China by dividing the sample cities into tourist and non-tourist cities.
Improvement of supplier delivery performance under uncertain capacity allocation and delivery time window
Authors: Sakhare Chirag Suresh , Chakraborty Sayan , Sarmah Sarada Prasad , Singh Vijay 
Published: June 2023

PurposeOriginal equipment manufacturers and other manufacturing companies rely on the delivery performance of their upstream suppliers to maintain a steady production process. However, supplier capacity uncertainty and delayed delivery often poses a major concern to manufacturers to carry out their production plan as per the desired schedules. The purpose of this paper is to develop a decision model that can improve the delivery performance of suppliers to minimise fluctuations in the supply quantity and the delivery time and thus maximising the performance of the supply chain.Design/methodology/approachThe authors studied a single manufacturer – single supplier supply chain considering supplier uncertain capacity allocation and uncertain time of delivery. Mathematical models are developed to capture expected profit of manufacturer and supplier under this uncertain allocation and delivery behaviour of supplier. A reward–penalty mechanism is proposed to minimise delivery quantity and time of delivery fluctuations from the supplier. Further, an order-fulfilment heuristic based on delivery probability is developed to modify the order quantity which can maximise the probability of a successful deliveries from the supplier.FindingsAnalytical results reveal that the proposed reward–penalty mechanism improves the supplier delivery consistency. This consistent delivery performance helps the manufacturer to maintain a steady production schedule and high market share. Modified ordering schedule developed using proposed probability-based heuristic improves the success probability of delivery from the supplier.Practical implicationsPractitioners can benefit from the findings of this study to comprehend how contracts and ordering policy can improve the supplier delivery performance in a manufacturing supply chain.Originality/valueThis paper improves the supplier delivery performance considering both the uncertain capacity allocation and uncertain time of delivery.
Three lines model paradigm shift: a blockchain-based control framework
Authors: Brender Nathalie , Gauthier Marion , Morin Jean-Henry , Salihi Arber 
Published: June 2023

PurposeWhile the three lines model (TLM) provides an organizational structure to execute risk and control duties, research and practice show limitations in the model's implementation. These limitations result in governance issues. Such issues, together with control weaknesses, could be addressed by leveraging properties of distribution, transparency, and immutability of blockchain technology. To this end, in this paper the authors propose a conceptual control framework based on blockchain technology to augment control practice.Design/methodology/approachThe design of the resulting blockchain-based control framework (BBCF) and its prototype, based on the design science research methodology (DSRM), is presented and discussed in terms of the potential impact in the context of the identified problems within the TLM.FindingsOne potential outcome of BBCF could be to redefine the scope and boundaries of some of the activities in audit and control practices from a more static to a more dynamic and prospective role. In a larger context of improving governance practices, the BBCF could set the path for a more inclusive and participatory interaction between the different governance actors of an organization.Research limitations/implicationsHowever, this assumes that blockchain is more widely adopted despite its complexity and rigidity.Practical implicationsBBCF covering both a conceptual model design and a reference implementation provides an innovation in audit and control. BBCF could include all relevant stakeholders who have an interest in corporate governance and control activities, including the regulators.Originality/valueThe contribution intends to serve both as a starting point for discussing the evolution of audit and control practice based on blockchain technology, as well as an initial actionable prototype for experimentation and further development.
Are animal personality, body condition, physiology and structural size integrated? A comparison of species, populations and sexes, and the value of study replication
Authors: Gaona‐Gordillo Irene , Holtmann Benedikt , Mouchet Alexia , Hutfluss Alexander , Sánchez‐Tójar Alfredo , Dingemanse Niels J. 
Published: June 2023

AbstractA major question in behavioural ecology is why behaviour, physiology and morphology are often integrated into syndromes. In great tits,Parus major, for example, explorative males are larger (vs. smaller) and leaner (vs. heavier) compared to less explorative individuals. Unfortunately, considerable debate exists on whether patterns found in specific studies are replicable. This debate calls for study replication among species, populations and sexes.We measured behavioural (exploration), physiological (breathing rate) and morphological traits (body mass, tarsus length, wing length, bill length) in two species (great vs. blue titsCyanistes caeruleus), two populations (Forstenrieder Park vs. Starnberg) and two sexes (males vs. females). We then tested whether the same pattern of integration characterized all unique combinations of these three biological categories (hereafter called datasets).We used a multi‐year repeated measures set‐up to estimate among‐individual trait correlation matrices for each dataset. We then used structural equation modelling to test for size‐dependent behaviour and physiology, size‐corrected (i.e. size‐independent) behaviour‐physiology correlations and size‐corrected body mass‐dependent behaviour and physiology. Finally, we used meta‐analyses to test which structural paths were generally (vs. conditionally) supported (vs. unsupported).We found general and consistent support for size‐dependent physiology and size‐corrected body mass‐dependent physiology across datasets: faster breathers were smaller but heavier for their size. Unexpectedly, condition‐dependent behaviour was not supported: explorative birds were neither leaner, nor was this relationship heterogeneous across datasets. All other hypothesized patterns were dataset‐specific: the covariance between size and behaviour, and between behaviour and physiology differed in sign between datasets, and both were, on average, not supported. This heterogeneity was not explained by any of our moderators: species, population or sex.The specific pattern of size‐ and condition‐dependent physiology reported for a unique combination of species, population, and sex, thus generally predicted those in others. Patterns of size‐ or condition‐dependent behaviour (i.e. ‘personality’), or behaviour‐physiology syndromes reported in specific datasets, by contrast, did not. These findings call for studies revealing the ecological background of this variation and highlight the value of study replication to help understand whether patterns of phenotypic integration reported in one study can be generalized.