bluuebunny/crossref_metadata_2025 huggingface dataset:
EMC is required for biogenesis and membrane insertion of Xport-A, an essential chaperone of rhodopsin-1 and the TRP channel
Authors: Gaspar Catarina J. , Vieira Lígia C. , Christianson John C. , Jakubec David , Strisovsky Kvido , Adrain Colin , Domingos Pedro M.
Published: February 2021

Insertion of hydrophobic transmembrane domains (TMDs) into the endoplasmic reticulum (ER) lipid bilayer is an essential step during eukaryotic membrane protein biogenesis. The ER membrane complex (EMC) functions as an insertase for TMDs of low hydrophobicity and is required for the biogenesis of a subset of tail-anchored (TA) and polytopic membrane proteins, including rhodopsin-1 (Rh1) and the TRP channel. To better understand the physiological implications of membrane protein biogenesis dependent on the EMC, we performed a bioinformatic analysis to predict TA proteins present in theDrosophilaproteome. From 254 predicted TA proteins, subsequent genetic screening inDrosophilalarval eye discs led to the identification of 2 proteins that require EMC for their biogenesis: farinelli (fan) and Xport-A. Fan is required for sperm individualization and male fertility inDrosophilaand we now show that EMC is also required for these important biological processes. Interestingly, Xport-A is essential for the biogenesis of both Rh1 and TRP, raising the possibility that disruption of Rh1 and TRP biogenesis in EMC loss of function mutations is secondary to the Xport-A defect. We show that EMC is required for Xport-A TMD membrane insertion and increasing the hydrophobicity of Xport-A TMD rendered its membrane insertion to become EMC-independent. Moreover, these EMC-independent Xport-A mutants rescued Rh1 and TRP biogenesis in EMC mutants. Our data establish that EMC can impact the biogenesis of polytopic membrane proteins indirectly, by controlling the biogenesis and membrane insertion of an essential protein co-factor.
Non-Canonical Projections from Ventral CA1 and Subicular Complex to CA3 Augments the Feedforward Hippocampal Trisynaptic Pathway
Authors: Lin Xiaoxiao , Amalraj Michelle , Blanton Crisylle , Avila Brenda , Holmes Todd C. , Nitz Douglas A. , Xu Xiangmin
Published: February 2021

The hippocampal formation is well documented as having a feedforward, unidirectional circuit organization termed the trisynaptic pathway. This circuit organization exists along the septotemporal axis of the hippocampal formation, but the circuit connectivity across septal to temporal regions is less well described. The emergence of viral-genetic mapping techniques enhances our ability to determine the detailed complexity of hippocampal formation circuitry. In earlier work, we mapped a subiculum back-projection to CA1 prompted by the discovery of theta wave back-propagation from the subiculum to CA1 and CA3. We reason that this circuitry may represent multiple extended non-canonical pathways involving the subicular complex and hippocampal subregions CA1 and CA3. In the present study, multiple retrograde viral tracing approaches produced robust mapping results, which supports this prediction. We find significant non-canonical synaptic inputs to dorsal hippocampal CA3 from ventral CA1, perirhinal cortex, and the subicular complex. Thus, CA1 inputs to CA3 run opposite the trisynaptic pathway and in a temporal to septal direction. Our retrograde viral tracing results are confirmed by anterograde-directed viral mapping of projections from input mapped regions to hippocampal dorsal CA3. Together, our data provide a circuit foundation to explore novel functional roles contributed by these non-canonical hippocampal circuit connections to hippocampal dynamics and behavior.
Variation inLeishmaniachemokine suppression driven by diversification of the GP63 virulence factor
Authors: Antonia Alejandro L. , Martin Amelia T. , Wang Liuyang , Ko Dennis C.
Published: February 2021

Leishmaniasis is a neglected tropical disease with diverse infection outcomes ranging from self-healing lesions, to progressive non-healing lesion, to metastatic spread and destruction of mucous membranes. Although resolution of cutaneous leishmaniasis is a classic example of type-1 immunity leading to well controlled self-healing lesions, an excess of type-1 related inflammation can contribute to immunopathology and metastatic spread of disease.Leishmaniagenetic diversity can contribute to variation in polarization and robustness of the immune response through differences in both pathogen sensing by the host and immune evasion by the parasite. In this study, we observed a difference in parasite chemokine suppression between theLeishmania (L.)subgenus and theViannia (V.)subgenus, which is associated with severe immune mediated pathology such as mucocutaneous leishmaniasis. WhileLeishmania (L.)subgenus parasites utilize the virulence factor and metalloprotease glycoprotein-63(gp63)to suppress the type-1 associated host chemokine CXCL10,L. (V.) panamensisdid not suppress CXCL10. To understand the molecular basis for the inter-species variation in chemokine suppression, we usedin silicomodeling of the primary amino acid sequence and protein crystal structures to identify a putative CXCL10-binding site on GP63. We found the putative CXCL10 binding site to be located in a region ofgp63under significant positive selection and that it varies from theL. majorwild-type sequence in allgp63alleles identified in theL. (V.) panamensisreference genome. We determined that the predicted binding site and adjacent positively selected amino acids are required for CXCL10 suppression by mutating wild-typeL. (L.) major gp63to theL. (V.) panamensisallele and demonstrating impaired cleavage of CXCL10 but not a non-specific protease substrate. Notably,Vianniaclinical isolates confirmed thatL. (V.) panemensisprimarily encodes non-CXCL10-cleavinggp63alleles. In contrast,L. (V.) braziliensishas an intermediate level of activity, consistent with this species having more equal proportions of both alleles at the CXCL10 binding site, possibly due to balancing selection. Our results demonstrate how parasite genetic diversity can contribute to variation in the host immune response toLeishmaniaspp. infection that may play critical roles in the outcome of infection.
Electrospun fibers for vaginal administration of tenofovir disoproxil fumarate and emtricitabine in the context of topical pre-exposure prophylaxis
Authors: Nunes Rute , Bogas Sarah , Faria Maria João , Gonçalves Hugo , Lúcio Marlene , Viseu Teresa , Sarmento Bruno , das Neves José
Published: February 2021

Women are particularly vulnerable to sexual HIV-1 transmission. Oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) is highly effective in avoiding new infections in men, but protection has only been shown moderate in women. Such differences have been associated, at least partially, to poor drug penetration of the lower female genital tract and the need for strict adherence to continuous daily oral intake of TDF/FTC. On-demand topical microbicide products could help circumventing these limitations. We developed electrospun fibers based on polycaprolactone (PCL fibers) or liposomes associated to poly(vinyl alcohol) (liposomes-in-PVA fibers) for the vaginal co-delivery of TDF and FTC, and assessed their pharmacokinetics in mice. PCL fibers and liposomes-in-PVA fibers were tested for morphological and physicochemical properties using scanning electron microscopy, differential scanning calorimetry and X-ray diffractometry. Fibers featured organoleptic and mechanical properties compatible with their suitable handling and vaginal administration. Fluorescent quenching of mucinin vitro– used as a proxy for mucoadhesion – was intense for PCL fibers, but mild for liposomes-in-PVA fibers. Both fibers were shown safein vitroand able to rapidly release drug content (15-30 min) under sink conditions. Liposomes-in-PVA fibers allowed increasing genital drug concentrations after a single intravaginal administration when compared to continuous daily treatment with 25-times higher oral doses. For instance, the levels of tenofovir and FTC in vaginal lavage were around 4- and 29-fold higher, respectively. PCL fibers were also superior to oral treatment, although to a minor extent (approximately 2-fold higher drug concentrations in lavage). Vaginal tissue drug levels were generally low for all treatments, while systemic drug exposure was negligible in the case of fibers. These data suggest that proposed fibers may provide an interesting alternative or an ancillary option to oral PrEP in women.
Crystal structure of fungal tannase from Aspergillus niger
Authors: Dong Liangbo , McKinstry William J. , Pan Li , Newman Janet , Ren Bin
Published: February 2021

Tannases are serine esterases that were first discovered in fungi more than one and half centuries ago. They catalyze the hydrolysis of the gallolyl ester bonds in gallotannins to release gallic acid, which is an important intermediate in the chemical and pharmaceutical industries. Since their discovery, fungal tannases have found wide industrial applications, although there is scarce knowledge about these enzymes at the molecular level, including their catalytic and substrate-binding sites. While this lack of knowledge hinders engineering efforts to modify the enzymes, many tannases have been isolated from various fungal strains in a search for the desired enzymatic properties. Here, the first crystal structure of a fungal tannase, that from Aspergillus niger, is reported. The enzyme possesses a typical α/β-hydrolase-fold domain with a large inserted cap domain, which together form a bowl-shaped hemispherical shape with a surface concavity surrounded by N-linked glycans. Gallic acid is bound at the junction of the two domains within the concavity by forming two hydrogen-bonding networks with neighbouring residues. One is formed around the carboxyl group of the gallic acid and involves residues from the hydrolase-fold domain, including those from the catalytic triad, which consists of Ser206, His485 and Asp439. The other is formed around the three hydroxyl groups of the compound, with the involvement of residues mainly from the cap domain, including Gln238, Gln239, His242 and Ser441. Gallic acid is bound in a sandwich-like mode by forming a hydrophobic contact with Ile442. All of these residues are found to be highly conserved among fungal and yeast tannases.
The effect of conservative financial reporting and tax aggressiveness on the market valuation of unrecognized tax benefits
Authors: Jiménez-Angueira Carlos E. , Nwaeze Emeka , Park Sung-Jin
Published: February 2021

Purpose

Prior studies document a positive relation between stock prices and tax-related contingent liability, unrecognized tax benefits (UTBs) and interpret the finding as evidence that investors reward tax aggressiveness. The purpose of this paper is to explore the nature of this puzzle finding by considering a link between UTBs and financial reporting strategy and propose that financial reporting conservatism may explain the positive association between UTBs and stock prices.

Design/methodology/approach

To estimate the incremental valuation weights on UTBs, the authors employ the Ohlson (1995) valuation model and regress stock prices on UTBs and its interactions with the proxies for financial reporting conservatism and tax aggressiveness. Further, the authors adopt a UTB estimation model to decompose its balance into the predicted and unpredicted components.

Findings

The authors find that the reporting conservatism has a positive effect on the market valuation of UTBs. The authors also find some evidence that tax aggressiveness increases the valuation weight of UTBs. When UTBs are decomposed into predicted and unpredicted components, the authors find that the effect of financial reporting conservatism is more pronounced for the market valuation of predicted UTBs. Collectively, the evidence suggests that conservative financial reporting is a major driver of the positive valuation of UTBs and that tax aggressiveness plays a less significant role in investors' valuation decisions.

Originality/value

While prior studies focus on how UTBs are associated with stock prices, this paper is the first attempt to explain why UTBs are positively valued by investors.
Examining antecedents of retail employees' propensity to leave
Authors: Park Jungkun , Ahn Jiseon , Hyun Hyowon , Rutherford Brian N.
Published: February 2021

Purpose

In this study, the authors examine the impacts of two facets of retail employees' cognitive support and affective commitment on emotional labor-related outcomes.

Design/methodology/approach

To test the study hypotheses, 521 retail service employees participated in the survey. By using the structural equation modeling, the results show that employees' perceived organizational support directly and positively employees' affective organizational commitment and emotional exhaustion.

Findings

By using the structural equation modeling, the results show that employees' perceived organizational support directly and positively influence employees' affective organizational commitment and emotional exhaustion. The extent of employees' affective organizational commitment directly and negatively influences emotional labor and exhaustion. Furthermore, employees' emotional exhaustion exerts an influence on retail employees' propensity to leave.

Research limitations/implications

Drawing on social exchange and conservation of resources theories, this study contributes to emotional labor research and practices by examining factors that potentially influences employees' propensity to leave. For future studies, researchers can expand the proposed framework of the current study to other retailing settings.

Practical implications

Findings of the study suggest that retail organizations need to manage employees' support and commitment concerning to understand emotional labor.

Originality/value

The current study found that employees' affective commitment influences key emotional labor constructs including emotional labor and emotional exhaustion. Employees who have a high level of identification, involvement and emotional attachment toward the organization, they are less likely to feel of overload and inefficiency. Given the importance of emotional labor in the retailing setting, the proposed model and findings of this study contribute the existing knowledge of retail employees' behavior.
Mothers, sons and daughters: intergenerational transmission of education in Canada
Authors: Latif Ehsan
Published: February 2021

Purpose

This study used data from the General Social Survey (2011) to examine the trends in intergenerational educational mobility in Canada for the 1940–1989 birth cohorts. To this end, the purpose of this study is to focus on the relationship between mothers' education and children's education.

Design/methodology/approach

The study estimated intergenerational regression and correlation coefficients and several mobility indices, namely, the Prais–Shorrocks index, immobility index, upward mobility index and downward mobility index.

Findings

The study found considerable gender differences with respect to the trends in these coefficients and indices. The study found that, over the period of study, the correlation coefficient slightly increased for sons while it decreased for daughters. The Prais–Shorrocks index, immobility index, upward mobility index and downward mobility index show that educational mobility has increased for daughters while that of sons has decreased over time. Finally, the relative educational opportunities indicators also suggest a similar result that educational mobility has increased for the daughters while it fell for the sons.

Originality/value

A number of studies used Canadian data to examine intergenerational educational mobility. However, no study particularly focused on the relationship between mothers' education and children's education. In recent years, women's labor force participation rate and employment rate increased significantly. Thus, it will be interesting to see how mothers' education is related to children's education in Canada.
Management accounting practices and efficiency in a Colombian multi-utility conglomerate
Authors: Barrios Álvarez Claudia , Adhikari Pawan , Gómez Mejía Alina
Published: February 2021

Purpose

The purpose of this paper is to examine how a state-owned Colombian multi-utility conglomerate (CMC) has used management accounting practices (MAPs) to shape efficiency. The authors bring out the interplay between structures and agency in the process of shaping efficiency, which has enabled the company to operate as a private enterprise, taking advantage of NPM-led reforms and management accounting technologies.

Design/methodology/approach

This is an interpretative case study of a CMC. Data for the study are derived from interviews, non-participative observations and document analysis. Giddens' structuration theory (ST) provides the theoretical approach for the study.

Findings

Results show that MAPs have shaped efficiency in a CMC, promoting the profitability criteria prevailing in private enterprises. Theoretically, the paper shows how structure and agency are embedded in shaping efficiency in an emerging economy context through MAPs. It does this by analysing both the broader influence of the School of Mines and multilateral development banks and the micro-situated practices of employees at the CMC. The employees who have worked in the company for long periods of time have transformed the profitability criteria into a corporate value that influences their day-to-day practices.

Originality/value

The paper adds to the literature that draws on the ST by illustrating a paradigmatic case, in which agents have brought in knowledge and values to a state-owned company, and changed its ethos and practices whilst remaining under state control.
Endoplasmic reticulum stress and collagenous formation anomalies in vascular‐type Ehlers–Danlos syndrome via electron microscopy
Authors: Ishikawa Satoko , Kosho Tomoki , Kaminaga Tomoko , Miyamoto Manabu , Hamasaki Yoichiro , Yoshihara Shigemi , Hayashi Shujiro , Igawa Ken
Published: February 2021

Vascular‐type Ehlers–Danlos syndrome (vEDS) is an autosomal‐dominant inherited disorder caused by a deficit in collagen III. It results from heterogeneous mutations in the α1 collagen III gene (COL3A1) and is associated with life‐threatening complications, even in younger patients. However, the details of the pathogenesis underlying the COL3A1 mutation causing vEDS remain unclear. Here, we focus on anomalies in collagen fiber size and the endoplasmic reticulum (ER) stress response in patients with vEDS using electron microscopy (EM). We discovered that although the infants did not have vEDS, collagenous formations were similar to their samples in vEDS. Moreover, we examined the expression of activating transcription factor 6 (ATF6) as an ER stress marker and cartilage oligomeric matrix protein (COMP) as a binding partner protein for collagen fibrils in the dermis and COL3A1. The expression levels of ATF6 in the vEDS group were significantly higher than in infants and controls; COMP and COL3A1 levels were significantly lower. The fragile collagen fibrils in vEDS might form as a result of ER stress and that small, newly formed collagen fibrils may appear. This research revealed a novel prospect regarding an issue that has been unclear for a long time, which is the reason for the abnormal sizes of collagenous fibrils in vEDS.
Dendritic cells inclusion and cell‐subset assessment improve flow‐cytometry‐based proliferation test in non‐immediate drug hypersensitivity reactions
Authors: Fernandez‐Santamaria Ruben , Bogas Gador , Palomares Francisca , Salas Maria , Fernandez Tahia D. , Jimenez Isabel , Barrionuevo Esther , Doña Inmaculada , Torres Maria Jose , Mayorga Cristobalina
Published: February 2021

Background

Lymphocyte transformation test (LTT) has been widely used to evaluate non‐immediate drug hypersensitivity reactions (NIDHRs). However, the lack of standardization and the low sensitivity have limited its routine diagnostic use. The drug presentation by dendritic cells (DCs) and the assessment of proliferation on effector cells have shown promising results. Flow‐cytometry‐based methods can help apply these improvements. We aimed to assess the added value of using drug‐primed‐DCs and the determination of the proliferative response of different lymphocyte subpopulations in NIDHRs.

Methods

Patients with confirmed NIDHR were evaluated by both conventional (C‐LTT) and with drug‐primed‐DCs LTT (dDC‐LTT)analysing the proliferative response in T cells and other effector cell subpopulations by using the fluorescent molecule, carboxyfluorescein diacetate succinimidyl ester (CFSE).

Results

The C‐LTT showed a significantly lower sensitivity (29.4%) compared with dDC‐LTT (61.8%), which was confirmed analysing each particular clinical entity: SJS‐TEN (62.5% vs 87.5%), MPE (15% vs 47.4%) and AGEP (33% vs 80%). When including the effector cell subpopulations involved in each clinical entity, CD3++CD4+Th1 or CD3++NK cells in SJS‐TEN, CD3++CD4+Th1+NK cells in MPE and CD3++NK cells in AGEP, we could significantly increase the sensitivity of thein vitrotest to 100%, 68.4% and 100%, respectively, with an overall sensitivity of 87% and 85% of specificity in NIDHR.

Conclusions

The use of a flow‐cytometry‐based test, DCs as drug presenting cells, and focusing on effector cell subpopulations for each clinical entity significantly improved the drug‐specific proliferative response in NIDHRs with a unique cellularin vitrotest.
Makeshift camp methodologies along the Balkan Route
Authors: Minca Claudio
Published: February 2021

This paper reflects on some of the methodological challenges I was faced with during my recent fieldwork in refugee camps along the Balkan Route. In particular, I will discuss the difficulties related to the application of conventional research methods in a context largely determined by “irregular” mobilities and by changing relationships between formal and informal camps. In‐depth interviews, go‐along interviews, participant observation, and other methods were crucially affected by the camp context, including its visible and invisible structures of power. After briefly discussing the role played by the Serbian authorities in defining our work in “the field,” the article analyses how doing fieldwork in this specific context required endless methodological adjustments, especially when it concerned our encounters with refugees living in camps and the necessity to take into full account the precarious conditions in which interviews took place. The second part of the article, focused in particular on the methodological implications of working in refugee makeshift camps, interrogates the reliability of the information obtained under such peculiar conditions and the ethical concerns associated with our positioning when visiting informal refugee encampments along the Balkan Route. Questions related to the study of makeshift camps will also be analysed together with the need to adapt (often, “on site”) our methods to “camp circumstances” and to produce potential counter‐cartographies of refugee informal mobilities.
Are the concerns destroying mental health of college students?: A qualitative analysis portraying experiences amidst COVID‐19 ambiguities
Authors: Gupta Riya , Agrawal Rachna
Published: February 2021

Coronavirus presenting an unforeseeable chain of events has exaggerated misery for students in India as they attracted the most detrimental experiences associated with lockdown restrictions leading to a shutdown of colleges as a preventive measure. The research endeavors to furnish a review of the overall hardships and psychological state of mind of college students and improvement in the implementation of policy decisions. Researchers conceptualize the newly discovered phenomenon by adopting grounded theory. Data from 256 newspaper articles, online articles and magazines have been gathered and converted into 256 separate files. To broaden the justification of research, social media analysis employing tweets, Facebook posts and Whatsapp messages are considered adding to the contributory prospects of the study. Compiled data is then refined through data mining technique. Triangulation approach amalgamating content analysis and thematic analysis has been deployed, thereby exploring the qualitative aspect of data gathering. Reviews from 31 students through telephonic conversation and 8 academic experts extended more accuracy to the research process. Findings administered academic disruptions with career concern, emotional suffering, financial concern, online learning, overseas injustice and psychological effects as the final themes representing various concerns experienced by college students. Hence, this work concludes with some constructive suggestions to deteriorate the amplified concerns.
Tropisetron balances immune responses via TLR2, TLR4 and JAK2/STAT3 signalling pathway in LPS‐stimulated PBMCs
Authors: Karimollah Alireza , Hemmatpur Anahid , Hosseini Nafise , Manshadi Mahdi Dehghan
Published: February 2021

Numerous documents have been stated that tropisetron, an antagonist of the 5‐HT3 receptor and α7nAChR agonist, modulates immune responses. However, the mechanistic basis for this aspect of tropisetron action is largely unknown. Here, the immuno‐modulatory effects of tropisetron are investigated, focusing on the possible molecular targets and the mechanisms. Aside from the well‐characterized role in immune signalling, JAK2/STAT3, TLR2 and TLR4 are signal transducers linked to both immuno‐modulatory actions of acetylcholine and serotonin. Therefore, we evaluated their involvement in the immunoregulatory effects of tropisetron. To test the hypothesis, we assessed the expression of pro‐/anti‐inflammatory cytokines including TNF‐α, IL‐1β, IL‐17 and IL‐10 following tropisetron treatment in lipopolysaccharide (LPS)‐stimulated peripheral blood mononuclear cells (PBMCs) derived from healthy subjects. Tropisetron up‐regulates the transcription of TLR2, TLR4, JAK2 and STAT3 genes. Tropisetron also increases the expression of target pro‐inflammatory cytokines, although considerably suppresses the pro‐inflammatory cytokines (IL‐1β, IL‐17 and TNF‐α) levels in media. Tropisetron notably promotes both IL‐10 gene expression and secretion. These findings confirm the antiphlogistic properties of tropisetron. The present data also shed light on a new aspect of tropisetron immune‐modulatory action that engaged TLR2, TLR4 and JAK2/STAT3 signalling cascades.
Ebselen reduces cigarette smoke‐induced endothelial dysfunction in mice
Authors: Brassington Kurt , Chan Stanley M. H. , Seow Huei Jiunn , Dobric Aleksandar , Bozinovski Steven , Selemidis Stavros , Vlahos Ross
Published: February 2021

Background and Purpose

It is well established that both smokers and patients with COPD are at a significantly heightened risk of cardiovascular disease (CVD), although the mechanisms underpinning the onset and progression of co‐morbid CVD are largely unknown. Here, we explored whether cigarette smoke (CS) exposure impairs vascular function in mice and given the well‐known pathological role for oxidative stress in COPD, whether the antioxidant compound ebselen prevents CS‐induced vascular dysfunction in mice.

Experimental Approach

Male BALB/c mice were exposed to either room air (sham) or CS generated from nine cigarettes per day, 5 days a week for 8 weeks. Mice were treated with ebselen (10 mg·kg−1, oral gavage once daily) or vehicle (5% w/v CM cellulose in water) 1 h prior to the first CS exposure of the day. Upon killing, bronchoalveolar lavage fluid (BALF) was collected to assess pulmonary inflammation, and the thoracic aorta was excised to investigate vascular endothelial and smooth muscle dilator responses ex vivo.

Key Results

CS exposure caused a significant increase in lung inflammation which was reduced by ebselen. CS also caused significant endothelial dysfunction in the thoracic aorta which was attributed to a down‐regulation of eNOS expression and increased vascular oxidative stress. Ebselen abolished the aortic endothelial dysfunction seen in CS‐exposed mice by reducing the oxidative burden and preserving eNOS expression.

Conclusion and Implications

Targeting CS‐induced oxidative stress with ebselen may provide a novel means for treating the life‐threatening pulmonary and cardiovascular manifestations associated with cigarette smoking and COPD.
Single systemic right ventricle longitudinal strain: Intravendor reproducibility and intervendor agreement in children
Authors: Colquitt John L. , Wilkinson J. Chris , Liu Asela M. , Pignatelli Ricardo H. , Loar Robert W.
Published: February 2021

Purpose

Strain derived from speckle‐tracking echocardiography is emerging as a useful tool in the assessment of single ventricle function. The purpose of this study is to compare layer‐specific longitudinal strain values in children with single, systemic right ventricles (sRV) using two commercially available software platforms (GE EchoPAC (EP) and TomTec (TT)).

Methods

Two readers analyzed two‐dimensional longitudinal strain on EP (v 202) and TT (v 2.21.25) in 40 pediatric sRV patients. Intravendor reproducibility and intervendor agreement between layer‐specific measurements were assessed by intraclass correlation coefficient and Bland–Altman analysis. Absolute difference (AbΔ) and relative mean errors (RME) were calculated. Subgroup comparisons (stratified by age, heart rate (HR), and frames per second (FPS): HR ratio) were made.

Results

Median age was 4.4 years. 32 (80%) patients had hypoplastic left heart syndrome; 19 (48%) were post‐Fontan. Intravendor reproducibility was excellent with high ICC (0.86‐0.97). AbΔ between readers was small (1.2%‐1.5%) with interobserver RME slightly higher for TT (11%‐12% vs 8%‐9% for EP). Layer‐specific intervendor agreement was poor (ICC 0.45‐0.62). Default layer comparisons (EP mid vs TT endo) showed good agreement (ICC 0.72‐0.77) and less variability (AbΔ 2%, RME 15%) than layer‐to‐layer. There were no differences in ICC for groups dichotomized by age, HR, or FPS:HR ratio. sRV strain values are more negative when using EP.

Conclusion

Intravendor reproducibility for sRV peak longitudinal strain in children is excellent with acceptable variability between experienced users. Intervendor, layer‐specific strain agreement is poor. Vendor default layer strain values show better agreement but are not interchangeable.
Evolution of honey resistance in experimental populations of bacteria depends on the type of honey and has no major side effects for antibiotic susceptibility
Authors: Bischofberger Anna M. , Pfrunder Cardozo Katia R. , Baumgartner Michael , Hall Alex R.
Published: February 2021

With rising antibiotic resistance, alternative treatments for communicable diseases are increasingly relevant. One possible alternative for some types of infections is honey, used in wound care since before 2000 BCE and more recently in licensed, medical‐grade products. However, it is unclear whether medical application of honey results in the evolution of bacterial honey resistance and whether this has collateral effects on other bacterial traits such as antibiotic resistance. Here, we used single‐step screening assays and serial transfer at increasing concentrations to isolate honey‐resistant mutants of Escherichia coli. We only detected bacteria with consistently increased resistance to the honey they evolved in for two of the four tested honey products, and the observed increases were small (maximum twofold increase in IC90). Genomic sequencing and experiments with single‐gene knockouts showed a key mechanism by which bacteria increased their honey resistance was by mutating genes involved in detoxifying methylglyoxal, which contributes to the antibacterial activity of Leptospermum honeys. Crucially, we found no evidence that honey adaptation conferred cross‐resistance or collateral sensitivity against nine antibiotics from six different classes. These results reveal constraints on bacterial adaptation to different types of honey, improving our ability to predict downstream consequences of wider honey application in medicine.
Pediatric high‐grade glioma: moving toward subtype‐specific multimodal therapy
Authors: Chatwin Hannah V. , Cruz Cruz Joselyn , Green Adam L.
Published: February 2021

Pediatric high‐grade gliomas (pHGG) comprise a deadly, heterogenous category of pediatric gliomas with a clear need for more effective treatment options. Advances in high‐throughput molecular techniques have enhanced molecular understanding of these tumors, but outcomes are still poor, and treatments beyond resection and radiation have not yet been clearly established as standard of care. In this review, we first discuss the history of treatment approaches to pHGG to this point. We then review four distinct categories of pHGG, including histone 3‐mutant, IDH‐mutant, histone 3/IDH‐wildtype, and radiation‐induced pHGG. We discuss the molecular understanding of each subgroup and targeted treatment options in development. Finally, we look at the development and current status of two novel approaches to pHGG as a whole: localized convection‐enhanced chemotherapy delivery and immunotherapy, including checkpoint inhibitors, vaccine therapy, and CAR‐T cells. Through this review, we demonstrate the potential for rational, molecularly driven, subtype‐specific therapy to be used with other novel approaches in combinations that could meaningfully improve the prognosis in pHGG.
Ginsenoside Rb3 alleviates smoke‐induced lung injury via the H19/miR‐29b‐3p/HGMB1/TLR4 signalling pathway
Authors: Tan Yan , Sun Danxiong , Chen Juan , Li Rufang , Wang Shenglan
Published: February 2021

The over‐activation of inflammation is involved in the pathogenesis of smoke‐induced lung injury (SILI), while Rb3 treatment may alleviate smoke‐induced lung injury by down‐regulating the expression of H19, a regulator of miR‐29b expression. Moreover, HMGB1 is an important mediator of inflammation. Therefore, in this study, we set up an animal model of SILI and treated it with Rb3 to study the effect of Rb3 on the treatment of SILI and the involvement of H19/miR‐29b/HMGB1/TLR4 signalling. SILI mice treated with Rb3 before H&E staining and TUNEL assay were conducted to observe the pathological damages and status of apoptosis in each group. Real‐time PCR, Western blot, computational analysis and luciferase assays were utilized to establish the signalling pathway involved in the pathogenesis of SILI and the action of Rb3 treatment. Rb3 treatment alleviated pathological changes in the lungs while decreasing the levels of W/D ratio and cell apoptotic index. H19 was validated to sponge miR‐29b‐3p, while HMGB1 mRNA was validated to be a target gene of miR‐29b‐3. As a result, a signalling pathway of H19/miR‐29b‐3p/HMGB1 was established. Cell viability was evidently reduced after 72 hours of treatment with CSE, but the treatment of Rb3 elevated the expression of H19 and HMBG1 in the presence of CSE. Also, CSE‐induced inhibition of miR‐29b‐3p expression was restored by Rb3. The findings of this study collectively demonstrated that Rb3 exhibited its therapeutic effect during the treatment of SILI via modulating the H19/miR‐29b‐3p/HMBG1 signalling pathway.
Designing Better Interventions: Insights from Research on Decent Work
Authors: Hasle Peter , Vang Jan
Published: February 2021

Based on our experience of carrying out theoretically and practically sound interventions to improve working conditions in global supply chains, we show what makes interventions succeed or fail and what is required to ensure that an intervention’s results are sustainable in the future. Our suggestions are applicable to designing any intervention in supply chain research, but need tailoring to the local context. Our interventions were aimed at achieving decent working conditions in emerging‐country suppliers, but our insights are applicable for all supply chain scholars. In the context of emerging‐country suppliers, poor working conditions have been strongly criticized after the Rana Plaza accident and subsequently received more attention with the UN’s introduction of the Sustainable Development Goals (notably, SDG 8). Tensions between productivity‐enhancing and decent work logics create challenges for the design of interventions with long‐lasting performance improvements. This paper presents a way of overcoming the tensions by illustrating how interventions that integrate improvements in working conditions with productivity can be designed.
Exploration of the dietary habits, lifestyle patterns and barriers to healthy eating in UK post‐partum women
Authors: Stevens R. , Kelaiditi E. , Myrissa K.
Published: February 2021

Maternal nutrition during the post‐partum period (PPP) is important for optimal health. The aim of this study was to explore dietary habits, lifestyle patterns and barriers to healthy eating in post‐partum women. An online survey exploring eating habits, weight status, sleep duration, breastfeeding, nutrition knowledge, physical activity, provision of advice and barriers to healthy eating was completed by 228 women (56.1% were 25–34 years, mean PPP of 5.73 ± 3.31 months). A sub‐sample of 34 women (50% were 35–44 years) completed an optional online multiple‐pass 24‐hour recall. At 6 months post‐partum (n = 60), 72.3% of participants weighed more than their pre‐pregnancy weight (mean 5.56 ± 4.61 kg). In addition, while 60.8% (n = 107) of women had a healthy body mass index (BMI) pre‐pregnancy, this dropped to 46.7% (n = 77) in the PPP. Only 2.2% of women were meeting current UK physical activity guidelines and 73.7% were not meeting the 5 A DAY fruit and vegetable recommendations. Consumption of high calorie snacks and meal skipping were significantly higher during the PPP compared to pre‐pregnancy (P < 0.01). Meal skipping was significantly associated with poor nutrition knowledge (P < 0.05). Women who were breastfeeding had significantly lower BMI than those who were bottle‐feeding after adjusting for age of baby, education, socio‐economic status and BMI pre‐pregnancy (P < 0.05). Fatigue, lack of time and feeling stressed were the most common self‐reported barriers to healthy eating, and these were greater for women with low combined household income and those having ≥3 children (P < 0.05). Dietary analysis showed that women were not meeting the national recommendations for energy, fibre, iron and vitamin D. Diet and lifestyle advice given to post‐partum women needs to be tailored to different sociodemographic characteristics, pre‐pregnancy health status and baseline nutrition knowledge, with a greater focus on those experiencing more barriers to healthy eating.
Single cell gene regulatory networks in plants: Opportunities for enhancing climate change stress resilience
Authors: Tripathi Rajiv K. , Wilkins Olivia
Published: February 2021

Global warming poses major challenges for plant survival and agricultural productivity. Thus, efforts to enhance stress resilience in plants are key strategies for protecting food security. Gene regulatory networks (GRNs) are a critical mechanism conferring stress resilience. Until recently, predicting GRNs of the individual cells that make up plants and other multicellular organisms was impeded by aggregate population scale measurements of transcriptome and other genome‐scale features. With the advancement of high‐throughput single cell RNA‐seq and other single cell assays, learning GRNs for individual cells is now possible, in principle. In this article, we report on recent advances in experimental and analytical methodologies for single cell sequencing assays especially as they have been applied to the study of plants. We highlight recent advances and ongoing challenges for scGRN prediction, and finally, we highlight the opportunity to use scGRN discovery for studying and ultimately enhancing abiotic stress resilience in plants.
Teaching math modeling through 3D‐printing: Examining the influence of an integrative professional development
Authors: Asempapa Reuben S. , Love Tyler S.
Published: February 2021

Mathematical modeling is a critical component of the current K–12 mathematics, science, and technology and engineering (T&E) educational standards in the United States. However, mathematical modeling is often overlooked or underemphasized in integrative STEM lessons. This could be attributed to teachers’ limited content and pedagogical knowledge related to integrating mathematical modeling in integrative STEM lessons. Continual advances in technologies like 3D design and printing software and additive manufacturing processes now allow students to see abstract mathematical modeling concepts in contextualized and practical forms. Consequently, we examined changes in mathematics, science, and T&E teachers’ mathematical modeling knowledge and views resulting from a 1‐day integrative professional development (PD) experience. The PD specifically focused on applying mathematical modeling concepts to design and 3D print solutions to integrative STEM lessons. A sample of 50 participating teachers reported increases in certain mathematical modeling knowledge areas, and a large percentage indicated they were more likely to implement mathematical modeling in their classrooms. The results from this study indicated that integrative PD could enhance teachers’ content knowledge, practices, and views about integrative STEM lessons including mathematical modeling and 3D printing. The findings from this study have implications for teachers, school districts, researchers, and professional development providers.
Effect of zinc content on the microstructure, in vitro bioactivity, and corrosion behavior of the microarc oxidized Mg–xZn–0.6Ca (x = 3.0, 4.5, 6.0) alloy
Authors: Wang Jingtao , Pan Yaokun , Wang Wei , Cui Hongwei , Feng Rui , Cui Xiaoli , Gong Benkui , Zhao Xingchuan , Hou Ning
Published: February 2021

Bioceramic calcium phosphorus (CaP) coatings were prepared on self-designed Mg–xZn–0.6Ca (x = 3.0, 4.5, 6.0 wt. %) alloy by microarc oxidation (MAO). The corrosion resistance, bioactivity, and biodegradability of the CaP coatings prepared on alloys with different zinc (Zn) contents were systematically studied and discussed by potentiodynamic polarization and in vitro immersion tests in the simulated body fluid solution. The CaP coatings and corrosion products were characterized by scanning electron microscopy, energy dispersive spectrometry, x-ray diffraction, and Fourier transform infrared spectroscopy. Based on the difference of microstructure caused by zinc content, the effect of microstructure on the properties of MAO coatings was analyzed by taking grain boundary and second phase defects as examples. Results showed that the CaP coatings could be prepared on the surface of the self-designed Mg–Zn–0.6Ca alloy by MAO. The CaP coatings have good bioactivity. Meanwhile, the Zn content has a significant effect on the microstructure of the CaP coatings. When the Zn content is 3.0 wt. %, the corrosion resistance and biocompatibility of the CaP coatings are obviously improved with good biological properties.
Atomic layer deposition of TbF3 thin films
Authors: Atosuo Elisa , Ojala Juha , Heikkilä Mikko J. , Mattinen Miika , Mizohata Kenichiro , Räisänen Jyrki , Leskelä Markku , Ritala Mikko
Published: February 2021

Lanthanide fluoride thin films have gained interest as materials for various optical applications, including electroluminescent displays and mid-IR lasers. However, the number of atomic layer deposition (ALD) processes for lanthanide fluorides has remained low. In this work, we present an ALD process for TbF3 using tris(2,2,6,6-tetramethyl-3,5-heptanedionato)terbium and TiF4 as precursors. The films were grown at 175–350 °C. The process yields weakly crystalline films at the lowest deposition temperature, whereas strongly crystalline, orthorhombic TbF3 films are obtained at higher temperatures. The films deposited at 275–350 °C are exceptionally pure, with low contents of C, O, and H, and the content of titanium is below the detection limit (<0.1 at. %) of time-of-flight elastic recoil detection analysis (ToF-ERDA). Due to the lack of titanium impurities, the films show high transmittance down to short UV wavelengths.
Analysing spectral changes over time to identify articulatory impairments in dysarthria
Authors: Slis A. , Lévêque N. , Fougeron C. , Pernon M. , Assal F. , Lancia L.
Published: February 2021

Identifying characteristics of articulatory impairment in speech motor disorders is complicated due to the time-consuming nature of kinematic measures. The goal is to explore whether analysing the acoustic signal in terms of total squared changes of Mel-Frequency Cepstral Coefficients (TSC_MFCC) and its pattern over time provides sufficient spectral information to distinguish mild and moderate dysarthric French speakers with Amyotrophic Lateral Sclerosis (ALS) and Parkinson's Disease (PD) from each other and from healthy speakers. Participants produced the vowel-glide sequences /ajajaj/, /ujujuj/, and /wiwiwi/. From the time course of TSC_MFCCs, event-related and global measures were extracted to capture the degree of acoustic change and its variability. In addition, durational measures were obtained. For both mild and moderately impaired PD and ALS speakers, the degree of acoustic change and its variability, averaged over the complete contour, separated PD and ALS speakers from each other and from healthy speakers, especially when producing the sequences /ujujuj/ and /wiwiwi/. Durational measures separated the moderate ALS from healthy and moderate PD speakers. Using the approach on repetitive sequences targeting the lingual and labial articulators to characterize articulatory impairment in speech motor disorders is promising. Findings are discussed against prior findings of articulatory impairment in the populations studied.
Automated two-dimensional localization of underwater acoustic transient impulses using vector sensor image processing (vector sensor localization)
Authors: Thode Aaron M. , Conrad Alexander S. , Ozanich Emma , King Rylan , Freeman Simon E. , Freeman Lauren A. , Zgliczynski Brian , Gerstoft Peter , Kim Katherine H.
Published: February 2021

Detecting acoustic transients by signal-to-noise ratio (SNR) becomes problematic in nonstationary ambient noise environments characteristic of coral reefs. An alternate approach presented here uses signal directionality to automatically detect and localize transient impulsive sounds collected on underwater vector sensors spaced tens of meters apart. The procedure, which does not require precise time synchronization, first constructs time-frequency representations of both the squared acoustic pressure (spectrogram) and dominant directionality of the active intensity (azigram) on each sensor. Within each azigram, sets of time-frequency cells associated with transient energy arriving from a consistent azimuthal sector are identified. Binary image processing techniques then link sets that share similar duration and bandwidth between different sensors, after which the algorithm triangulates the source location. Unlike most passive acoustic detectors, the threshold criterion for this algorithm is bandwidth instead of pressure magnitude. Data collected from shallow coral reef environments demonstrate the algorithm's ability to detect SCUBA bubble plumes and consistent spatial distributions of somniferous fish activity. Analytical estimates and direct evaluations both yield false transient localization rates from 3% to 6% in a coral reef environment. The SNR distribution of localized pulses off Hawaii has a median of 7.7 dB and interquartile range of 7.1 dB.