bluuebunny/crossref_metadata_2025 huggingface dataset:
Heparan sulfate modifications of betaglycan promote TIMP3-dependent ectodomain shedding to fine-tune TGF-β signaling
Authors: Choi Alex S , Jenkins-Lane Laura M , Barton Wade , Kumari Asha , Lancaster Carly , Raulerson Calen , Ji Hao , Altomare Diego , Starr Mark D , Whitaker Regina , Phaeton Rebecca , Arend Rebecca , Shtutman Michael , Nixon Andrew B , Hempel Nadine , Lee Nam Y , Mythreye Karthikeyan
Published: August 2023

In pathologies such as cancer, aberrant Transforming Growth Factor-β (TGF-β) signaling exerts profound tumor intrinsic and extrinsic consequences. Intense clinical endeavors are underway to target this pivotal pathway. Central to the success of these interventions is pinpointing factors that decisively modulate the TGF-β responses. Betaglycan/type III TGF-β receptor (TβRIII), is an established co-receptor for the TGF-β superfamily known to bind directly to TGF-βs 1-3 and inhibin A/B. While betaglycan can be membrane-bound, it can also undergo ectodomain cleavage to produce soluble-betaglycan that can sequester its ligands. The extracellular domain of betaglycan undergoes heparan sulfate and chondroitin sulfate glycosaminoglycan modifications, transforming betaglycan into a proteoglycan. Here we report the unexpected discovery that the heparan sulfate modifications are critical for the ectodomain shedding of betaglycan. In the absence of such modifications, betaglycan is not shed. Such shedding is indispensable for the ability of betaglycan to suppress TGF-β signaling and the cells’ responses to exogenous TGF-β ligands. Using unbiased transcriptomics, we identified TIMP3 as a key regulator of betaglycan shedding and thereby TGF-β signaling. Our results bear significant clinical relevance as modified betaglycan is present in the ascites of patients with ovarian cancer and can serve as a marker for predicting patient outcomes and TGF-β signaling responses. These studies are the first to demonstrate a unique reliance on the glycosaminoglycan modifications of betaglycan for shedding and influence on TGF-β signaling responses. Dysregulated shedding of TGF-β receptors plays a vital role in determining the response and availability of TGF-βs’, which is crucial for prognostic predictions and understanding of TGF-β signaling dynamics.
Rab7a activation promotes degradation of select tight junction proteins at the blood-brain barrier after ischemic stroke
Authors: Cottarelli Azzurra , Shahriar Sanjid , Arac Ahmet , Glendinning Michael , Tuohy Mary Claire , Prochilo Grace , Neal Jason B. , Edinger Aimee L. , Agalliu Dritan
Published: August 2023

The stability of tight junctions (TJs) between endothelial cells (ECs) is essential to maintain blood-brain barrier (BBB) function in the healthy brain. Following ischemic stroke, TJ strand dismantlement due to protein degradation leads to BBB dysfunction, yet the mechanisms driving this process are poorly understood. Here, we show that endothelial-specific ablation of Rab7a, a small GTPase that regulates endolysosomal protein degradation, reduces stroke-induced TJ strand disassembly resulting in decreased paracellular BBB permeability and improved neuronal outcomes. Two pro-inflammatory cytokines, TNFα and IL1β, but not glucose and oxygen deprivation, induce Rab7a activation via Ccz1 in brain ECsin vitro, leading to increased TJ protein degradation and impaired paracellular barrier function. Silencing Rab7a in brain ECsin vitroreduces cytokine-driven endothelial barrier dysfunction by suppressing degradation of a key BBB TJ protein, Claudin-5. Thus, Rab7a activation by inflammatory cytokines promotes degradation of select TJ proteins leading to BBB dysfunction after ischemic stroke.
The mechanism ofGαqregulation ofPLCβ3-catalyzedPIP2hydrolysis
Authors: Falzone Maria E. , MacKinnon Roderick
Published: August 2023

PLCβenzymes cleavePIP2producing IP3 and DAG.PIP2modulates the function of many ion channels, while IP3 and DAG regulate intracellular Ca2+levels and protein phosphorylation by protein kinase C, respectively.PLCβenzymes are under the control of GPCR signaling through direct interactions with G proteinsGβγandGαqand have been shown to be coincidence detectors for dual stimulation ofGαqand Gαicoupled receptors.PLCβsare aqueous-soluble cytoplasmic enzymes, but partition onto the membrane surface to access their lipid substrate, complicating their functional and structural characterization. Using newly developed methods, we recently showed thatGβγactivatesPLCβ3by recruiting it to the membrane. Using these same methods, here we show thatGαqincreases the catalytic rate constant,kcat, ofPLCβ3. Since stimulation ofPLCβ3byGαqdepends on an autoinhibitory element (the X-Y linker), we propose thatGαqproduces partial relief of the X-Y linker autoinhibition through an allosteric mechanism. We also determined membrane-bound structures of thePLCβ3-Gαq,andPLCβ3-Gβγ(2)-Gαqcomplexes, which show that these G proteins can bind simultaneously and independently of each other to regulatePLCβ3activity. The structures rationalize a finding in the enzyme assay, that co-stimulation by both G proteins follows a product rule of each independent stimulus. We conclude that baseline activity ofPLCβ3is strongly suppressed, but the effect of G proteins, especially acting together, provides a robust stimulus upon G protein stimulation.

Significance Statement

For certain cellular signaling processes, the background activity of signaling enzymes must be minimal and stimulus-dependent activation robust. Nowhere is this truer than in signaling byPLCβ3, whose activity regulates intracellular Ca2+, phosphorylation by Protein Kinase C, and the activity of numerous ion channels and membrane receptors. In this study we show howPLCβ3enzymes are regulated by two kinds of G proteins,GβγandGαq. Enzyme activity studies and structures on membranes show how these G proteins act by separate, independent mechanisms, leading to a product rule of co-stimulation when they act together. The findings explain how cells achieve robust stimulation ofPLCβ3in the setting of very low background activity, properties essential to cell health and survival.
Shifting Redox Reaction Equilibria on Demand Using an Orthogonal Redox Cofactor
Authors: Aspacio Derek , Zhang Yulai , Cui Youtian , King Edward , Black William B. , Perea Sean , Luu Emma , Siegel Justin B. , Li Han
Published: August 2023

Natural metabolism relies on chemical compartmentalization of two redox cofactors, NAD+and NADP+, to orchestrate life-essential redox reaction directions. However, in whole cells the reliance on these canonical cofactors limits flexible control of redox reaction direction as these reactions are permanently tied to catabolism or anabolism. In cell-free systems, NADP+is too expensive in large scale. We have previously reported the use of nicotinamide mononucleotide, (NMN+) as a low-cost, noncanonical redox cofactor capable of specific electron delivery to diverse chemistries.

Here, we present Nox Ortho, an NMNH-specific water-forming oxidase, that completes the toolkit to modulate NMNH/NMN+ratio. This work uncovers an enzyme design principle that succeeds in parallel engineering of six butanediol dehydrogenases as NMN(H)-orthogonal biocatalysts consistently with a 103– 106-fold cofactor specificity switch from NAD(P)+to NMN+. We combine these to produce chiral-pure 2,3-butanediol (Bdo) isomers without interference from NAD(H) or NADP(H) in vitro and inE. colicells. We establish that NMN(H) can be held at a distinct redox ratio on demand, decoupled from both NAD(H) and NADP(H) redox ratios in vitro and in vivo.
Genetic code expansion, click chemistry, and light-activated PI3K reveal details of membrane protein trafficking downstream of receptor tyrosine kinases
Authors: Koh Duk-Su , Stratiievska Anastasiia , Jana Subhashis , Otto Shauna C. , Swanson Teresa M. , Nhim Anthony , Carlson Sara , Raza Marium , Naves Lígia Araujo , Senning Eric N. , Mehl Ryan A. , Gordon Sharona E.
Published: August 2023

ABSTRACT

Ligands such as insulin, epidermal growth factor, platelet derived growth factor, and nerve growth factor (NGF) initiate signals at the cell membrane by binding to receptor tyrosine kinases (RTKs). Along with G-protein coupled receptors, RTKs are the main platforms for transducing extracellular signals into intracellular signals. Studying RTK signaling has been a challenge, however, due to the multiple signaling pathways to which RTKs typically are coupled, including MAP/ERK, PLCγ, and Class 1A phosphoinositide 3-kinases (PI3K). The multi-pronged RTK signaling has been a barrier to isolating the effects of any one downstream pathway. Here, we used optogenetic activation of PI3K to decouple its activation from other RTK signaling pathways. In this context, we used genetic code expansion to introduce a click chemistry noncanonical amino acid into the extracellular side of membrane proteins. Applying a cell- impermeant click chemistry fluorophore allowed us to visualize delivery of membrane proteins to the plasma membrane in real time. Using these approaches, we demonstrate that activation of PI3K, without activating other pathways downstream of RTK signaling, is sufficient to traffic the TRPV1 ion channels and insulin receptors to the plasma membrane.
Targeting the glycan epitope type IN-acetyllactosamine enables immunodepletion of human pluripotent stem cells from early differentiated cells
Authors: Rossdam Charlotte , Brand Smilla , Beimdiek Julia , Oberbeck Astrid , Albers Marco Darius , Naujok Ortwin , Buettner Falk F. R.
Published: August 2023

Cell surface biomarkers are fundamental for specific characterization of human pluripotent stem cells (hPSCs). Importantly, they can be applied for hPSC enrichment and/or purification but also to remove potentially teratoma-forming hPSCs from differentiated populations before clinical application. Several specific markers for hPSCs are glycoconjugates comprising the glycosphingolipid (GSL)-based glycans SSEA-3 and SSEA-4. We applied an analytical approach based on multiplexed capillary gel electrophoresis coupled to laser-induced fluorescence detection to quantitatively assess the GSL glycome of human embryonic stem cells and human induced pluripotent stem cells as well as during early stages of differentiation into mesoderm, endoderm, and ectoderm. Thereby, we identified the GSL lacto-N-tetraosylceramide (Lc4-Cer, Galβ1-3GlcNAcβ1-3Galβ1-4Glc-Cer), which comprises a terminal type 1 LacNAc (T1LN) structure (Galβ1-3GlcNAc), to be rapidly decreased upon onset of differentiation. Using a specific antibody, we could confirm a decline of T1LN-terminating glycans during the first four days of differentiation by live-cell staining and subsequent flow cytometry. We could further separate T1LN-positive and T1LN-negative cells out of a mixed population of pluripotent and differentiated cells by magnetic activated cell sorting. Notably, not only the T1LN-positive but also the T1LN-negative population was positive for SSEA-3, SSEA-4, and SSEA-5 while expression of nuclear pluripotency markersOCT4andNANOGwas highly reduced in the T1LN-negative population, exclusively. Our findings suggest T1LN as a pluripotent stem cell-specific glycan epitope that is more rapidly down-regulated upon differentiation than SSEA-3, SSEA-4, and SSEA-5.
Metabolic partitioning in the brain and its hijacking by glioblastoma
Authors: de Ruiter Swain Jed , Michalopoulou Evdokia , Noch Evan K. , Lukey Michael J. , Van Aelst Linda
Published: August 2023

The different cell types in the brain have highly specialized roles with unique metabolic requirements. Normal brain function requires the coordinated partitioning of metabolic pathways between these cells, such as in the neuron–astrocyte glutamate–glutamine cycle. An emerging theme in glioblastoma (GBM) biology is that malignant cells integrate into or “hijack” brain metabolism, co-opting neurons and glia for the supply of nutrients and recycling of waste products. Moreover, GBM cells communicate via signaling metabolites in the tumor microenvironment to promote tumor growth and induce immune suppression. Recent findings in this field point toward new therapeutic strategies to target the metabolic exchange processes that fuel tumorigenesis and suppress the anticancer immune response in GBM. Here, we provide an overview of the intercellular division of metabolic labor that occurs in both the normal brain and the GBM tumor microenvironment and then discuss the implications of these interactions for GBM therapy.
The assessment of biophilic features in residential buildings: a case from Dubai
Authors: Shakhshir Kulthoum , Sheta Wael
Published: August 2023

Purpose

This study explores the difference in occupants' satisfaction with biophilic features in high-rises, townhouses, and villas in Dubai to identify new strategies that promote more human-nature connections. The study also serves as a benchmark for applying Biophilic Design in the Gulf region and bridging between biophilic theory and practice.

Design/methodology/approach

A mixed-mode approach was used, combining surveys from occupants and interviews with experts (3 policymakers, a developer, and a biophilic design educator). The survey collected occupants' satisfaction and acceptance of proposed strategies, and the interviews validated the potentially accepted solutions.

Findings

The results indicated high overall satisfaction with biophilic features despite neutral/low satisfaction with specific features. In high-rise buildings, respondents showed high acceptance for different proposed strategies; 76.4% for adaptive control of balconies by season, 82.7% for utilizing outdoor roof gardens, 78.9% for indoor gardens, and 71.8% for vertical farming. Additionally, respondents accepted social strategies; 63.6% agreed to join clubs promoting environmental events, and 75.4% accepted participating in outdoor recreational activities accompanied by local environmental education. The interviews showed an inclination toward incentive programs instead of obligations.

Originality/value

Unlike former studies that assessed indoor environmental qualities without referring to biophilic theory or limited reference to biophilic design, this study provides a novel approach for bridging theory and practice by integrating biophilic design into residential buildings for Dubai's future developments. Additionally, the authors suggest validated proposals to enhance the occupants' biophilic living experience, serving as a benchmark for biophilic application in the Gulf region.
How might responsible management education (RME) be used to develop responsible leadership skills among students in business schools? Evidence from non-Western business schools
Authors: Mousa Mohamed , del Aguila Levy , Abdelgaffar Hala
Published: August 2023

Purpose

This paper aims to find an answer to the questions: To what extent is the implementation of responsible management education (RME) perceived to be adequate for developing responsible leadership skills among business school students? How should it be used effectively to guarantee such an outcome?

Design/methodology/approach

The authors conducted semi-structured interviews with 24 management educators working at three public business schools. Thematic analysis was used to analyse the collected data.

Findings

The findings show that the implementation of RME alone is not adequate to ensure the development of responsible leadership skills among students in business schools. However, management educators do perceive it as a considerable step towards that outcome if accompanied with internship and training opportunities to exercise and observe how social roles and activities are practiced in business, not-for-profit and civil society organisations.

Originality/value

This study is a pioneering attempt to address the relationship between RME and developing responsible leadership skills among students in non-Western business schools.
How education and training systems can support a digitally-enabled workforce for the manufacturing industry of the future: an exploratory study
Authors: Laundon Melinda , McDonald Paula , Greentree Jacqueline
Published: August 2023

Purpose

This paper explores how education and training systems can support a digitally-enabled workforce for the Australian manufacturing sector.

Design/methodology/approach

The study is based on interviews with 17 sector-level manufacturing stakeholders from industry, government and education/training organisations. Semi-structured interviews were conducted to gain an in-depth understanding of how education and training systems currently support a digitally-enabled manufacturing workforce as well as opportunities for alternative configurations or developments.

Findings

Analysis revealed three themes reflecting core dimensions of a supportive education and training system: partnerships, pedagogy and prospects. Cooperative, integrated and sustained partnerships are needed between vocational education and training (VET) institutions, universities, government, industry, high schools and private training providers. Pedagogy emphasises the vital importance of infusing curriculum with digital and technology skills and capabilities, alongside innovative and experiential delivery modes including simulated environments, online learning, on-the-job training, flexible delivery and micro-credentials. Prospects reflects the need for forward-looking assessment and planning to respond to industry trends and develop associated qualifications, skills and investments required to meet future industry needs.

Originality/value

With growing demand for digitally-enabled skills to support manufacturing, an industry which is acknowledged as critical for economic prosperity and national sovereignty, the findings contribute novel insights into current limitations and future opportunities to bridge the gap between skills shortages in the manufacturing industry, and education and training systems that deliver graduate readiness and a digitally-enabled workforce.
Exploring digital transformation and technological innovation in emerging markets
Authors: Malekpour Mehrgan , Sedighi Mohammadbashir , Caboni Federica , Basile Vincenzo , Troise Ciro
Published: August 2023

Purpose

This research aims to fill the research gaps regarding customer preferences for digitalisation to create value for retailers and customers, as well as focus on retail change and shopping behaviour in grocery retail stores in the emerging market.

Design/methodology/approach

This paper contributes to the research in this area by evaluating customers' and retailers' attitudes towards digital transformation in retailing through interviews. Methodologically, 200 questionnaires were gathered, and data were analysed with the partial least squared structural equation modelling method.

Findings

The findings of this study reveal that the effect of digital transformation in the retail industry will be more apparent in an emerging market.

Originality/value

The paper's originality consists in understanding the future retail structure in an emerging market. Notably, focussing on business-to-consumer businesses appears helpful in distinguishing between behavioural (buying) intention and online buying behaviour (actual usage) in an emerging market.
Governmental financial resilience during pandemics: the case of West Africa
Authors: Agyemang Jacob , Azure John , Kimani Danson , Arun Thankom
Published: August 2023

Purpose

The paper examines financial resilience responses/capacities of governments from Liberia, Sierra Leone and Ghana in relation to COVID-19. It highlights the governments’ fiscal, budgetary and actions as either anticipatory or coping mechanisms towards the pandemic.

Design/methodology/approach

Multiple case studies and secondary data were used, including official government documentation/records, expert views, policy publications by supranational organisations and international financial institutions and media reports. Textual analysis was conducted to evaluate the case countries’ resilience.

Findings

The paper highlights how governmental budgetary initiatives, including repurposing the manufacturing sector, can sustain businesses, aid social interventions and reduce vulnerability during health crises. In addition, the paper highlights that external borrowing continues to be indispensable in the financial and budgetary initiatives of the case countries. The paper finds that lessons learnt from the Ebola Virus Disease (EVD) in West Africa within the last decade have shaped the anticipatory resilience capacities of the case countries against COVID-19.

Originality/value

The paper uses the notion of resilience, the dimensions of the resilience framework and the resource-based view (RBV) theory to unearth resilience patterns. This sort of combined approach is new to financial resilience studies.
Social- or task-oriented: how does social crowding shape consumers' preferences for chatbot conversational styles?
Authors: Zhu Jiaji , Jiang Yushi , Wang Xiaoxuan , Huang Suying
Published: August 2023

Purpose

Driven by artificial intelligence technology, chatbots have begun to play an important customer service role in the online retail environment. This study aims to explore how conversational styles improve the interaction experience between consumers and chatbots in different social crowding environments, and the moderating role of product categories is considered.

Design/methodology/approach

Three studies are conducted to understand the influences of conversational styles, social crowding and product categories on consumer acceptance, assessed using situational experiments and questions.

Findings

In a low social crowding environment, consumers prefer chatbots with a social-oriented (vs. task-oriented) conversational style, while in a high social crowding environment, consumers prefer a task-oriented (vs. social-oriented) conversational style, and warmth and competence mediate these effects. The moderating effect of product categories is supported.

Originality/value

This study expands the application of the stereotype content model to improve the interaction experience level between consumers and chatbots in online retail. The findings can provide managerial suggestions for retailers to select a chatbot's conversational style and promote a more continuous interaction between consumers and chatbots.
Past, present and future of impact investing and closely related financial vehicles: a literature review
Authors: Chiappini Helen , Marinelli Nicoletta , Jalal Raja Nabeel-Ud-Din , Birindelli Giuliana
Published: August 2023

Purpose

The purpose of this study is to analyze the intersection of research on impact investing and its closely related financial vehicles.

Design/methodology/approach

The paper explores 196 articles collected from Scopus and Web of Science using bibliometric and content analysis methodologies.

Findings

Despite a growing academic interest in impact investing, scholars generally investigate impact investing as a social phenomenon, using the specific financial mechanism of social impact bonds. This perspective potentially deflates the complex nature of impact investing, which actually combines both social and financial targets and uses a plurality of financial vehicles to reach its goals.

Practical implications

The emerging themes identified will provide both academics and practitioners additional tools to further the debate on impact investing and the understanding of its potential and limits according to the different financial forms it takes. This review should pave the way for a discussion about the boundaries of the social impact sector itself.

Social implications

Despite the strong international commitment toward impact investing, tensions still exist. A comprehensive overview on the relevant aspects not yet thoroughly investigated will foster the growth of impact investments.

Originality/value

To the best of the authors’ knowledge, this is the first holistic overview of impact investing, that jointly examines both literature on impact investing and literature on the correlated financial products used in the industry. The result is a comprehensive report of what is known about impact investing in its different financial forms, opening up new pathways for future studies.
From words to action: unpacking the real impact of sustainability initiatives on carbon emissions reduction
Authors: Issa Ayman , In'airat Mohammad
Published: August 2023

Purpose

The purpose of this study is to analyze the correlation between a company’s efforts to reduce carbon emissions and its actual carbon performance. Additionally, the study investigates how female decision-makers may influence this relationship as moderators.

Design/methodology/approach

This study uses a data set consisting of 1,258 observations from companies listed on the STOXX Europe 600 index between 2009 and 2021. The study applies the ordinary least squares technique to investigate the connection between carbon reduction initiatives and actual carbon performance, taking into account the potential impact of board and executive gender diversity. To ensure the reliability of the findings, subsample analysis and a two-step generalized method of moments technique were used.

Findings

The results show a significant negative association between a firm’s commitment to environmental initiatives and its carbon emission intensity. Furthermore, the study explores the moderating effect of board and executive gender diversity on this relationship and finds that gender diversity has a significant negative impact on the relationship between emissions reduction initiatives and carbon emissions.

Practical implications

The study has practical implications for corporate sustainability efforts. It highlights the importance of implementing carbon reduction initiatives to effectively mitigate carbon emissions. This emphasizes the need for sustainable business strategies that prioritize environmental initiatives. Additionally, the study underscores the positive impact of gender diversity in leadership positions on carbon reduction efforts. Policymakers and organizations can leverage these findings to promote gender diversity and enhance sustainability practices.

Social implications

It provides evidence-based insights for policymakers to develop specific policies and action plans in priority areas such as climate change and emissions reduction. It also highlights the positive influence of gender diversity in corporate leadership on environmental initiatives, promoting inclusivity and equality in sustainability practices.

Originality/value

This study brings originality by investigating the direct impact of a company’s carbon reduction initiatives on its carbon performance. It also explores the moderating effect of board and executive gender diversity on this relationship. The study provides evidence-based insights for policymakers and applies neo-institutional theory to analyze the interplay between carbon reduction initiatives, carbon emissions and gender diversity in executive and board positions.
BMax consulting moves into Southeast Asia
Authors: Richardson Christopher , Foster Morris John
Published: August 2023

Research methodology

The data for this case were obtained primarily through a series of in-person interviews in Penang between the authors and Pete Browning (a pseudonym) from 2017 to early 2019. The authors also consulted secondary data sources, including publicly available material on BMax and “Company B”.

Case overview/synopsis

This case examines a key decision, or set of decisions, in the life of a small- to medium-sized management consultancy group, namely, whether they might expand their operations in Southeast Asia, and if so, where. These key decisions came in the wake of their having already established a very modest scale presence there, with an operating base on the island of Penang just off the north western coast of Peninsular Malaysia. The initial establishment of a Southeast Asian branch had been somewhat spontaneous in nature – a former colleague of one of the two managing partners in the USA was on the ground in Malaysia and available: he became the local partner in the firm. But the firm had now been eyeing expansion within the region, with three markets under particular consideration (Singapore, Indonesia and Thailand) and a further two (Vietnam and China) also seen as possible targets, though at a more peripheral level. The questions facing the decision makers were “was it time they expand beyond Malaysia?” and “if so, where?”

Complexity academic level

This case could be used effectively in undergraduate courses in international business. The key concepts on which the case focuses are the factors affecting market entry, particularly the choice of market and the assessment of potential attractiveness such markets offer.
Internal validation of reduced PCR reaction volume of the Qiagen Investigator® Argus X‐12 QS Kit from blood samples on FTA cards
Authors: Alwi Aedrianee Reeza , Mahat Naji Arafat , Mohd Salleh Faezah , Ishar Seri Mirianti , Kamaluddin Mohammad Rahim , Rashid Mohd Radzniwan A.
Published: August 2023

The onus of proof in criminal cases is beyond any reasonable doubt, and the issue on the lack of complete internal validation data can be manipulated when it comes to justifying the validity and reliability of the X‐chromosomal short tandem repeats analysis for court representation. Therefore, this research evaluated the efficiency of the optimized 60% reduced volumes for polymerase chain reaction (PCR) amplification using the Qiagen Investigator® Argus X‐12 QS Kit, as well as the capillary electrophoresis (CE) sample preparation for blood samples on Flinder's Technology Associates (FTA) cards. Good‐quality DNA profile (3000–12,000 RFU) from the purified blood sample on FTA card (1.2 mm) were obtained using the optimized PCR (10.0 μL of PCR reaction volume and 21 cycles) and CE (9.0 μL Hi‐Di™ Formamide and 0.3 μL DNA Size Standard 550 [BTO] and 27 s injection time) conditions. The analytical and stochastic thresholds were 100 and 200 RFU, respectively. Hence, the internal validation data supported the use of the optimized 60% reduced PCR amplification reaction volume of the Qiagen Investigator® Argus X‐12 QS Kit as well as the CE sample preparation for producing reliable DNA profiles that comply with the quality assurance standards for forensic DNA testing laboratories, while optimizing the analytical cost.
Land use and sexual harassment: A geospatial analysis based on the volunteer HarassMap‐Egypt
Authors: Al‐Sabbagh Tamer Ali , Li Yijing , Lee Yong Jei , El Kenawy Ahmed M.
Published: August 2023

Sexual harassment and gang rape in Egypt have garnered attention from both traditional and digital media. This study employed a volunteer HarassMap to analyse sexual harassment crimes (SHCs) across Egypt from a spatial perspective. The specific aims were to apply the Hierarchical Density‐Based Spatial Clustering of Applications with Noise (HDBSCAN) algorithm to locate clusters of reported SHCs, and to assess their spatial dependence on land use types. To accomplish this task, ring buffers of 100, 200, 300, 400, and 500 metres were established around each crime scene to determine which land use was mostly associated with the incidence of these SHCs. Local bivariate relationships were used to explore the associations between SHC and each land‐use category. Results from the HDBSCAN algorithm revealed four crime clusters within the study domain, mainly located in Greater Cairo, Alexandria, and Behaira. Notably, commercial establishments and transit stations showed a significantly positive correlation with SHC. The study shows how land uses shape SHC and showed that it is possible to identify environmental risk factors for harassment. These risk factors can help policymakers, urban planners, and community stakeholders prevent and reduce sexual harassment and gender inequality, and promote just and inclusive societies.
Exploring the geographies of transnational higher education in China
Authors: Li Yajuan , Song Congcong , Zhang Xu , Li Yibin
Published: August 2023

This paper contributes to debates about the globalisation of higher education by providing a pioneering geographical exploration of Chinese–foreign cooperation in running transnational higher education, or TNHE, programs. Departing from widespread neoliberal and postcolonial critiques of TNHE, which tend to emphasise liberal market forces and Anglo‐American hegemony in the circulation of academic knowledge, our study examines how the Chinese state’s developmental targets, strategic policies, and political–ideological considerations have shaped the evolutionary trajectory, geographical distribution, and cross‐border connections of China’s TNHE programs. We demonstrate that the place‐based development of TNHE is mediated by governments’ interventionist policies and embedded in existing higher education regimes, especially in the context of East Asian developmental states. By maintaining a higher education system dominated by public universities and by being the ultimate examination and approval authority, the Chinese government both determines the status of TNHE in the national higher education system, constrains the typologies and sources of knowledge flows, and shapes the national landscape of TNHE development. The territorial geographies of TNHE thus reflect complicated interactions between the state and the market, the global and the local, and economic and political/cultural forces.
Transferrin receptor levels and its rare variant are associated with human obesity
Authors: Qiu Jin , Zhang Zhiyin , Hu Yepeng , Guo Yuhan , Liu Caizhi , Chen Yanru , Wang Dongmei , Su Junlei , Wang Sainan , Ni Mengshan , Xu Sainan , Yu Jian , Hu Tianhui , Song Gaojie , Ma Xinran , Gu Xuejiang , Wang Jiqiu , Xu Lingyan
Published: August 2023

Aim

Iron homeostasis is critical for functional respiratory chain complex of mitochondrial, thus potentially contributing to fat biology and energy homeostasis. Transferrin receptor (Tfrc) binds to transferrin for extracellular iron uptake and is recently reported to be involved in brown fat development and functionality. However, whether TFRC levels and variants are associated with human obesity is unknown.

Methods

To investigate the association of TFRC levels and variants with human obesity, fat biopsies were obtained from surgery. Exon‐sequencing and genetic assessments were conducted of a case–control study. For TFRC levels assessment in fat biopsy, 9 overweight and 12 lean subjects were involved. For genetic study, obese (n = 1271) and lean subjects (n = 1455) were involved. TFRC levels were compared in abdominal mesenteric fat of pheochromocytoma patients versus control subjects, and overweight versus lean subjects. For genetic study, whole‐exome sequencing of obese and matched control subjects were conducted and analyzed. In addition, the possible disruption in protein stability of TFRC variant was assessed by structural and molecular analysis.

Results

TFRC levels are increased in human browning adipose tissue and decreased in fat of overweight patients. Besides, TFRC levels are negatively correlated with body mass index and positively correlated with uncoupling protein 1 levels. Furthermore, a rare heterozygous missense variant p.I337V in TFRC shows a tendency to enrich in obese subjects. Structural and functional study reveals impaired protein stability of the TFRC variant compared to wild‐type.

Conclusions

Reduced TFRC levels and its rare variant p.I337V with protein instability are associated with human obesity.
Multi‐trait point pattern reconstruction of plant ecosystems
Authors: Wudel Chris , Schlicht Robert , Berger Uta
Published: August 2023

Plants interact locally in many ways and the processes involved (e.g. competition for resources, natural regeneration, mortality or subsequent succession) are complex. These processes give rise to characteristic spatial patterns that vary over time. The corresponding spatial data, that is the locations of individuals and their specific characteristics (e.g. trees of a certain species and their diameters), are known as point patterns, and their statistical analysis can be used to study the underlying processes and their changes due to environmental scenarios. A special application of point pattern analysis is their numerical reconstruction, which is classically used (a) to generate null models that can be contrasted with observed patterns and (b) to evaluate the information contained in observed data using various summary statistics. Sometimes, the reconstructed datasets are also used to initialise individual‐based or agent‐based plant models with realistic but artificially generated data in order to analyse or forecast the development of plant systems.

Previous reconstruction methods of point patterns consider only one mark, or they consider several marks but neglect their correlations. We introduce a method that considers individual locations and two marks simultaneously (in our example information on tree species, and diameter at breast height). The method uses different summary statistics of the second‐order point pattern analysis, such as the pair correlation function and the mark correlation function. By successively modifying the reconstructed spatial pattern, the distance (also called energy), measured in terms of differences in the summary statistics between the generated pattern and the observed pattern, is minimised and a high statistical similarity is achieved.

After testing the method on different datasets, the suitability of our method for reconstructing complex spatial forest stands, including the spatial relationships of all considered marks, is shown.

The presented method is a powerful tool for generating point pattern data. With minor changes, it even enables the reconstruction of forest stands and plant systems larger than those used to collect the inventory data, and although we used two marks only to demonstrate the power of the method, it is easy to include more marks.
Accounting for unobserved spatial variation in step selection analyses of animal movement via spatial random effects
Authors: Arce Guillen Rafael , Lindgren Finn , Muff Stefanie , Glass Thomas W. , Breed Greg A. , Schlägel Ulrike E.
Published: August 2023

Step selection analysis (SSA) is a common framework for understanding animal movement and resource selection using telemetry data. Such data are, however, inherently autocorrelated in space, a complication that could impact SSA‐based inference if left unaddressed. Accounting for spatial correlation is standard statistical practice when analysing spatial data, and its importance is increasingly recognized in ecological models (e.g. species distribution models). Nonetheless, no framework yet exists to account for such correlation when analysing animal movement using SSA.

Here, we extend the popular method integrated step selection analysis (iSSA) by including a Gaussian field (GF) in the linear predictor to account for spatial correlation. For this, we use the Bayesian framework R‐INLA and the stochastic partial differential equations (SPDE) technique.

We show through a simulation study that our method provides accurate fixed effects estimates, quantifies their uncertainty well and improves the predictions. In addition, we demonstrate the practical utility of our method by applying it to three wolverine (Gulo gulo) tracks.

Our method solves the problems of assuming spatially independent residuals in the SSA framework. In addition, it offers new possibilities for making long‐term predictions of habitat usage.
Investigating cycle shifts in women's clothing style and grooming
Authors: Stern Julia , Ostermann Sabine , Penke Lars
Published: August 2023

In contrast to some non‐human primate species, human females do not show overt cues to fertility. Previous research argued that women still show systematic changes in their appearance across their ovulatory cycle to enhance their mating success when fertile. We report five studies investigating whether women's clothing style and grooming behaviour change across the ovulatory cycle. All studies were large (with N = 157 in Study 1, N = 109 in Study 2, N = 257 in Studies 3–5), longitudinal studies with four testing sessions per participant. They involved salivary hormone samples and luteinizing hormone tests to validate conception risk estimates. Across all studies, our results suggest no compelling evidence for cycle shifts in clothing style and grooming. Rather, two studies suggest effects in the opposite direction as hypothesized, as women wore more skin‐revealing clothes when non‐fertile. One study suggests small effects of wearing necklaces more and eyeglasses less often when fertile. However, these effects were not robust across all studies. Our results are in line with other recent null replications and suggest that, if existent, cues to fertility might be even more subtle than previously assumed. We discuss the need for testing competing theories that explain the evolution of concealed ovulation.
Alzheimer's disease phenotype based upon the carrier status of the apolipoprotein E ɛ4 allele
Authors: Ji Xiao‐Yu , Peng Xin‐Yuan , Tang Hai‐Liang , Pan Hui , Wang Wei‐Tang , Wu Jie , Chen Jian , Wei Nai‐Li
Published: August 2023

The apolipoprotein Eɛ4allele (APOE4) is universally acknowledged as the most potent genetic risk factor for Alzheimer's disease (AD).APOE4promotes the initiation and progression of AD. Although the underlying mechanisms are unclearly understood, differences in lipid‐bound affinity among the three APOE isoforms may constitute the basis. The protein APOE4 isoform has a high affinity with triglycerides and cholesterol. A distinction in lipid metabolism extensively impacts neurons, microglia, and astrocytes.APOE4carriers exhibit phenotypic differences from non‐carriers in clinical examinations and respond differently to multiple treatments. Therefore, we hypothesized that phenotypic classification of AD patients according to the status of APOE4 carrier will help specify research and promote its use in diagnosing and treating AD. Recent reviews have mainly evaluated the differences betweenAPOE4allele carriers and non‐carriers from gene to protein structures, clinical features, neuroimaging, pathology, the neural network, and the response to various treatments, and have provided the feasibility of phenotypic group classification based onAPOE4carrier status. This review will facilitate the application ofAPOEphenomics concept in clinical practice and promote further medical research on AD.
Is there a massive glacial–Holocene flora continuity in Central Europe?
Authors: Molnár Ábel Péter , Demeter László , Biró Marianna , Chytrý Milan , Bartha Sándor , Gantuya Batdelger , Molnár Zsolt
Published: August 2023

The prevailing paradigm about the Quaternary ecological and evolutionary history of Central European ecosystems is that they were repeatedly impoverished by regional extinctions of most species during the glacial periods, followed by massive recolonizations from southern and eastern refugia during interglacial periods. Recent literature partially contradicts this view and provides evidence to re‐evaluate this Postglacial Recolonization Hypothesis and develop an alternative one. We examined the long‐term history of the flora of the Carpathian (Pannonian) Basin by synthesising recent advances in ecological, phylogeographical, palaeoecological and palaeoclimatological research, and analysing the cold tolerance of the native flora of a test area (Hungary, the central part of the Carpathian Basin). We found that (1) many species have likely occurred there continuously since before the Last Glacial Maximum (LGM); (2) most of the present‐day native flora (1404 species, about 80%) can occur in climates as cold as or colder than the LGM (mean annual temperature ≤+3.5°C); and (3) grasslands and forests can be species‐rich under an LGM‐like cold climate. These arguments support an alternative hypothesis, which we call the Flora Continuity Hypothesis. It states that long‐term continuity of much of the flora in the Carpathian Basin is more plausible than regional extinctions during the LGM followed by massive postglacial recolonizations. The long‐term continuity of the region's flora may have fundamental implications not only for understanding local biogeography and ecology (e.g. the temporal scale of processes), but also for conservation strategies focusing on protecting ancient species‐rich ecosystems and local gene pools.
Real‐world outcomes of low‐dose atropine therapy on myopia progression in an Australian cohort during the COVID‐19 pandemic
Authors: Usmani Eiman , Callisto Stephanie , Chan Weng Onn , Taranath Deepa
Published: August 2023

Background

To report the outcomes of low‐dose atropine (0.01% and 0.05%) for preventing myopia progression in a real‐world Australian cohort during the COVID‐19 pandemic.

Methods

Records of children presenting with myopia, from January 2016 to 2022, were retrospectively reviewed at a comprehensive ophthalmic practice. Children who discontinued treatment, ages >18, and cases with hereditary conditions were excluded. The rate of progression of myopia after treatment with atropine was compared with historical data to evaluate the effectiveness of the regime.

Results

One hundred and one children (mean baseline spherical equivalent [SphE] [−3.70 +/− 2.09 D] and axial length [AL] [24.59 +/− 1.00 mm]) were analysed. The mean age of the children was 10.4 +/− 2.89 years and 61% were females. The average follow‐up time was 17.9 +/− 12.5 months. The mean rate of progression of AL and SphE on 0.01% atropine eyedrops was 0.219 +/− 0.35 mm and − 0.250 +/− 0.86 D/year, respectively. 68.1% of the children treated with 0.01% atropine were mild progressors (<0.5 D change/year). Non‐responders when commenced on a higher dose of atropine (0.05%) experienced a 93% (p = 0.012) and 30% reduction in SphE and AL growth rate, respectively. Family history, higher myopia or younger age at baseline and shorter duration of treatment were associated with steeper progression (p < 0.01). Both doses were well tolerated.

Conclusions

Low‐dose atropine was shown to be beneficial in a real‐world clinical setting, despite interruptions to follow‐ups secondary to COVID‐19 pandemic. A 0.05% dose of atropine may be effective in cases where 0.01% was ineffective.