bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibin A contributes to the tumorigenesis of oral squamous cell carcinoma by KIAA1429‐mediated m6A modification
Authors: Chen Xiaoqing , Fan Renxiu
Published: March 2024

Background

Inhibin A and N6‐methyladenosine methylation modifications participate in oral squamous cell carcinoma development. However, the N6‐methyladenosine modification of Inhibin A in oral squamous cell carcinoma has not been revealed. This study reveals a key gene “Inhibin A” that may affect the tumorigenesis of oral squamous cell carcinoma and its molecular mechanisms on N6‐methyladenosine methyltransferase KIAA1429‐mediated N6‐methyladenosine methylation modification.

Methods

Bioinformatics analysis and quantitative real‐time polymerase chain reaction identified the potential regulatory genes in oral squamous cell carcinoma. We examined the changes in the proliferation (Cell Counting Kit‐8 assay), migration (transwell migration assay), and invasion (transwell invasion assays) of oral squamous cell carcinoma cells. We performed a xenograft tumor experiment to validate the role of Inhibin A in oral squamous cell carcinoma in vivo. The interactions between Inhibin A and KIAA1429 were analyzed using bioinformatics, methylated RNA immunoprecipitation‐qPCR, quantitative real‐time polymerase chain reaction, and Western blotting experiments.

Results

Inhibin A had the highest expression in patients with oral squamous cell carcinoma. Inhibin A silencing impaired the ability of oral squamous cell carcinoma cells to proliferate, migrate, and invade, as well as limited the tumorous growth of oral squamous cell carcinoma cells in vivo. Bioinformatics analysis showed that Inhibin A expression positively interacted with KIAA1429 expression in The Cancer Genome Atlas database. The levels were also upregulated in our clinical samples. Furthermore, KIAA1429 silencing repressed the N6‐methyladenosine level of Inhibin A in oral squamous cell carcinoma.

Conclusions

Inhibin A promotes the tumorigenesis of oral squamous cell carcinoma by KIAA1429‐mediated N6‐methyladenosine modification. This study adds to our current knowledge of the molecular mechanisms underlying oral squamous cell carcinoma malignancy.
Local information and the stabilization role of local government: Evidence from a natural experiment in China
Authors: Jia Junxue , Li Rong , Liu Chang , Ning Jing
Published: March 2024

Oates, (1972) argues that local governments cannot use conventional policies to stabilize economies, due to fiscal spillovers and beggar‐thy‐neighbor policies. Hayek's theory implies it is efficient for a central government to devolve decision‐making authority to local governments that have informational advantages. This paper tests the different theoretical implications by examining a natural experiment caused by the income‐tax‐sharing reform in China. Our analysis reveals that local government size does have a stabilization effect, but vertical fiscal imbalance (VFI) substantially weakens this stabilizing effect; lack of local information is the key factor leading to this influence of VFI.
Mitigating the definitional quagmire in innovation research: An inclusive definition of innovation as a template for defining various types of innovations uniformly
Authors: Varadarajan Rajan
Published: March 2024

A review of research on innovation and new product development points to certain foundational issues of concern such as the use of (1) different definitions of constructs germane to the field (e.g., definitions of innovation, innovativeness, and specific types of innovations), (2) different construct labels to refer to specific innovation types, and (3) the same construct label to refer to different innovation types. Over the years, scholars have cautioned that a body of research in a field of study that is based on different definitions of constructs germane to the field would slow the advancement of knowledge. Against this backdrop, the purpose of this Catalyst paper is to initiate a conversation on the prospects for mitigating the definitional quagmire in research on innovation and new product development by developing an inclusive definition of innovation that can be used as a template for defining various types of innovations uniformly. Toward this end, the paper proposes an inclusive definition of innovation based on idea, outcome, and value creation as the defining or essential characteristics of all innovations. Definitions of 10 specific types of innovations defined in a consistent manner, employing the proposed inclusive definition of innovation as a template are also presented. All else being equal, consistency across research studies in the definitions of constructs employed can be conducive to the advancement of knowledge in a field of study in several ways such as streamlining the curation of the research‐based knowledge, facilitating the grounding of new research in prior research (i.e., curated knowledge), and eliminating differences across studies in the definitions of key constructs employed as a potential confound on the research findings.
Applying unoccupied aerial systems to assess genetic gain from mass selection for tembotrione tolerance in sorghum (Sorghum bicolor)
Authors: Crozier Daniel , Beechinor Kayla A. , Young Blake , Bagavathiannan Muthukumar , Rooney William L.
Published: March 2024

The post‐emergent herbicide options to control grasses in sorghum have historically been limited. Therefore, a mass selection program was implemented to increase the tolerance of sorghum to the broad‐spectrum herbicide tembotrione. The objectives of this study are to determine (i) which observation timing and vegetative indices are most effective in assessing sorghum injury to tembotrione using unoccupied aerial system imagery and (ii) if mass selection can be used to increase the tolerance of sorghum to tembotrione. Using an unoccupied aerial system, several vegetative indices, collected at either 14 or 21 days after tembotrione application, accurately measured sorghum injury. Over four cycles of selection, tembotrione tolerance increased in a linear and consistent manner. This demonstrates that mass selection can be used as a strategy for developing herbicide tolerance in crops. The modest, but steady genetic gain indicates both the quantitative nature of the trait and sufficient heritability to improve it. Given further development, tembotrione‐resistant sorghum hybrids could provide an effective means of post‐emergent weed control for a range of common weeds.
Co‐overexpression of SWEET sucrose transporters modulates sucrose synthesis and defence responses to enhance immunity against bacterial blight in rice
Authors: Singh Jitender , James Donald , Das Shubhashis , Patel Manish Kumar , Sutar Rashmi Ranjan , Achary V. Mohan Murali , Goel Naveen , Gupta Kapuganti Jagadis , Reddy Malireddy K. , Jha Gopaljee , Sonti Ramesh V. , Foyer Christine H. , Thakur Jitendra Kumar , Tripathy Baishnab C.
Published: March 2024

Enhancing carbohydrate export from source to sink tissues is considered to be a realistic approach for improving photosynthetic efficiency and crop yield. The rice sucrose transporters OsSUT1, OsSWEET11a and OsSWEET14 contribute to sucrose phloem loading and seed filling. Crucially, Xanthomonas oryzae pv. oryzae (Xoo) infection in rice enhances the expression of OsSWEET11a and OsSWEET14 genes, and causes leaf blight. Here we show that co‐overexpression of OsSUT1, OsSWEET11a and OsSWEET14 in rice reduced sucrose synthesis and transport leading to lower growth and yield but reduced susceptibility to Xoo relative to controls. The immunity‐related hypersensitive response (HR) was enhanced in the transformed lines as indicated by the increased expression of defence genes, higher salicylic acid content and presence of HR lesions on the leaves. The results suggest that the increased expression of OsSWEET11a and OsSWEET14 in rice is perceived as a pathogen (Xoo) attack that triggers HR and results in constitutive activation of plant defences that are related to the signalling pathways of pathogen starvation. These findings provide a mechanistic basis for the trade‐off between plant growth and immunity because decreased susceptibility against Xoo compromised plant growth and yield.
Evolution of decreased sensitivity to azole fungicides in western European populations of Plenodomus lingam (Phoma stem canker on oilseed rape)
Authors: King Kevin M. , Barr Leo , Bousquet Louise , Glaab Anna , Canning Gail , Ritchie Faye , Kildea Steven , Fraaije Bart A. , West Jonathan S.
Published: March 2024

Plenodomus lingam (Leptosphaeria maculans) and P. biglobosus (L. biglobosa) are fungi causing Phoma leaf spot/stem canker, an international damaging disease of oilseed rape (Brassica napus) and other brassicas. In Europe, fungicides used for disease management are mainly sterol 14α‐demethylase (CYP51) inhibitors (DMIs/azoles); quinone‐outside inhibitors (QoIs) and succinate dehydrogenase inhibitors (SDHIs) are also used. Decreased DMI sensitivity has emerged in Australian and eastern European P. lingam populations and is mediated by CYP51 promoter inserts resulting in target site overexpression. In this study using in vitro sensitivity testing, we report decreased DMI (prothioconazole‐desthio, mefentrifluconazole) sensitivity in modern western European P. lingam isolates (collected 2022–2023) compared to older baseline (1992–2005) isolates. Around 85% of modern western European P. lingam isolates collected, for which the CYP51 promoter region was sequenced, carried a promoter insert, but target site alterations were not detected. Six different CYP51 promoter inserts were identified, most commonly a 237 bp fragment of the Sahana transposable element. Inserts were associated with an approximately 3‐ to 10‐fold decrease in sensitivity to the DMIs tested. In contrast to P. lingam, PCR screening revealed CYP51 promoter inserts were absent in modern western European P. biglobosus isolates (2021–2023). Combined data indicate P. lingam isolates lacking an insert were similarly (or slightly more) sensitive to the DMIs tested for P. biglobosus, whereas those carrying an insert were slightly less sensitive than P. biglobosus. No evidence for substantive sensitivity shifts to the QoI (pyraclostrobin) or SDHI (boscalid) fungicides tested was obtained for either Plenodomus species.
Invisible plastics problem in intensive aquaculture: The case of polyvinylpyrrolidone
Authors: Robison‐Smith Charlotte , Cable Jo
Published: March 2024

For over 70 years, aquaculture practices have relied on the same methods for biosecurity, however epidemics remain a primary limitation of global aquaculture yields with billions in revenue being lost every year due to disease. The intense nature of fish and shellfish farming necessitates the regular use of synthetic chemicals as both preventive and treatment measures, covering broodstocks to hatching and continuing through all stages of rearing. This practice, however, results in the contamination of rearing environments with persistent xenobiotics. A specific drawback in this foundational strategy for aquaculture biosecurity is highlighted in the current review: the consistent use of a water‐soluble polymer polyvinylpyrrolidone (PVP) across most, if not all, stages of rearing aquacultural livestock. PVP is used intensively within aquaculture practices as it is a ubiquitous additive within commercially available germicidal, prophylactic, and therapeutic products applied to control and prevent disease outbreaks within aquacultural farms. As a polymer, PVP is synthetic and biodegradation‐resistant, and has recently been described as an emerging contaminant of freshwater ecosystems. It is well documented that other persistent, synthetic polymer pollutants such as microplastics, reduce the fecundity, growth, and significantly deplete immune function in commercially important aquatic species. Despite this, intentionally added persistent soluble polymers, such as PVP, have not been considered in the context of aquaculture productivity. This review explores the potential impact of PVP on fish and shellfish highlighting the need for aquaculture to adopt sustainable chemical practices, drawing inspiration from advancements in nanotechnology applied within human medicines to address biosecurity protocol deficiencies.
Facing and dealing with emotional turbulence: Living with newly diagnosed Parkinson's disease
Authors: Hammarlund Catharina Sjödahl , Khalaf Atika , Westergren Albert , Hagell Petra Lilja , Hagell Peter
Published: March 2024

Introduction

The experiences of living with Parkinson's disease (PD) from the perspective of newly diagnosed persons with PD (PwPD) have not been previously described.

Aim

This study aimed to gain a better understanding of the impact of living with the early stages of PD.

Methods

A qualitative interview study was conducted among nine persons, seven men and two women, from southern Sweden. Participants had a median age of 71 (min–max, 64–77) years and had been diagnosed with PD for a median of 5 (min–max, 2–12) months. Interviews were recorded and analysed using systematic text condensation.

Results

The analysis resulted in one core category, Facing and dealing with emotional turbulence, and four categories with 2–3 subcategories each: Something is wrong (Vague signs of change; Losing control); The going gets tough (Recalling; Lack of motivation); Losing direction (Uncertainties; Frightened of disease progression) and Dealing with life (Avoiding social situations; Hope and despair; Ease worries).

Conclusion

Newly diagnosed PwPD face emotional turbulence with increasing challenges in managing everyday basic needs. Impaired functioning affects self‐esteem and identity, which calls for strategies to overcome emotional reactions of embarrassment, frustration and worry. A sense of lost control and direction increased as the future became more uncertain. The participants’ emotional burden and struggle to find a reason to go on or some solution to their new situation left them with both hope and despair. Our results suggest that a person‐centred needs‐based approach may help newly diagnosed PwPD deal with their new life situation.
Trends in adherence to the 24‐h movement guidelines among US adolescents from 2011 to 2019: Evidence from repeated cross‐sectional cycles of the Youth Risk Behavior Surveillance System
Authors: Chen Sitong , Brown Denver , Parker Kate , Lee Eun‐Young
Published: March 2024

Background

Adherence to the 24‐h movement guidelines is associated with various health benefits, but given the novelty of these integrative recommendations, little is known about year‐to‐year trends in guideline adherence in adolescents. This study investigated trends of adherence to the 24‐h movement guidelines among US adolescents.

Methods

Data from 2011 to 2019 cycles of the Youth Risk Behavior Surveillance System were used, which included 62 589 US adolescents aged 14–17 years (female: unweighted sample size = 31 876, 51%; weighted% = 50.1%). Participants self‐reported their demographic information (i.e., sex, age, race/ethnicity), physical activity, screen time and sleep duration. Meeting the 24‐h movement guidelines was operationalized as simultaneously engaging in 60 min or more of moderate‐to‐vigorous physical activity, no more than 2 h of screen time, and 8–10 h of sleep per day. Trend analysis was used to examine the secular changes in adherence to the integrated guidelines from 2011 to 2019.

Results

Downward trends in adherence to the 24‐h movement guidelines were observed among adolescents from 2011 (3.6%) to 2019 (2.6%). After stratification by sex, age, and race/ethnicity, similar downward trends in the guideline adherence were observed in females and Black/African American adolescents. The lowest prevalence of meeting the individual guidelines was for the PA guidelines (25.6%). Movement guideline adherence was consistently lowest among females, older adolescents, and those who identified as Black/African American.

Conclusions

Adherence to the 24‐h movement guidelines has declined among US adolescents over the past decade. Interventions should prioritize an integrative approach that could increase concurrent adherence to each of the 24‐h movement guideline, particularly among female, older and minority adolescents.
Characterization of the in vivo transient responses of the femoral cartilage by means of quantitative ultrasound imaging techniques
Authors: Monte Andrea , Franchi Martino V. , Zamparo Paola
Published: March 2024

Background

Quantitative ultrasound (QUS) techniques are new diagnostic tools able to identify changes in structural and material properties of the investigated tissue. For the first time, we evaluated the capability of QUS techniques in determining the in vivo transient changes in knee joint cartilage after a stressful task.

Methods

An ultrasound scanner collecting B‐mode and radiofrequency data simultaneously was used to collect data from the femoral cartilage of the right knee in 15 participants. Cartilage thickness (CTK), ultrasound roughness index (URI), average magnitude ratio (AMR), and Nakagami parameters (NA) were evaluated before, immediately after and every 5 min up to 45 min a stressful task (30 min of running on a treadmill with a negative slope of 5%).

Results

CTK was affected by time (main effect: p < 0.001). Post hoc test showed significant differences with CTK at rest, which were observed up to 30 min after the run. AMR and NA were affected by time (p < 0.01 for both variables), while URI was unaffected by it. For AMR, post hoc test showed significant differences with rest values in the first 35 min of recovery, while NA was increased compared to rest values in all time points.

Conclusion

Data suggest that a single running trial is not able to modify the integrity of the femoral cartilage, as reported by URI data. In vivo evaluation of QUS parameters of the femoral cartilage (NA, AMR, and URI) are able to characterize changes in cartilage properties over time.
Long‐term application of different organic and inorganic fertilizers in no‐tillage crops changes the soil microstructural viscoelasticity and shear resistance to transient stresses
Authors: Alves Amanda Romeiro , Holthusen Dörthe , Marchezan Carina , Brunetto Gustavo , Peth Stephan , Reichert José Miguel
Published: March 2024

The processes involved in deformation, internal strength and stability of soils with long‐term application of fertilizers (organic and inorganic sources) remain poorly investigated and hence understood, particularly in agricultural systems under subtropical climatic conditions. We investigated how long‐term fertilizer management with organic and inorganic amendments in no‐till crops affects the microstructural stability of a sandy Alfisol under oscillatory shear. The study was conducted in southern Brazil on a 17‐year completely randomized block experiment with five fertilizer treatments: pig slurry (PS), cattle slurry (CS), pig deep litter (PDL), mineral fertilizer (MF) and control, i.e. unfertilized (CL). Soil samples were collected from two layers (0–5 and 5–15 cm) for physical and chemical analyses and evaluation of soil rheological properties under oscillatory shear at two matric potentials (0 and −10 kPa). Organic matter accumulation in soil provided by the PDL and CS fertilizers resulted in higher soil stability and elasticity under oscillatory shear, especially in the 0–5 cm layer. Conversely, MF and PS enhanced the soil susceptibility towards deformation under transient stresses, mainly in the 0–5 cm layer under saturated conditions. The PDL significantly increased soil shear resistance under low‐shear strain conditions. Significant differences ceased under high‐shear strain conditions, though PS and MF yielded at significantly lower strains. Hence, under subtropical conditions, long‐term application of organic fertilizers with fibrous components promoted soil microstructure strengthening, reducing soil susceptibility to erosive processes and compaction.
A proactive safety approach to delivering safer care in obstetrics and gynaecology
Authors: Pradhan Farrah , Cunningham Simon , Woodward Suzette
Published: March 2024

Key content

In obstetrics and gynaecology, things often ‘go well’ because clinicians make sensible adaptations in response to situations to ensure safety, often within a highly pressurised environment.

The adaptations and performance variables that are made under these complex circumstances are not explicitly understood.

Understanding the performance variability of clinicians as well as the environmental context that enables good or successful outcomes may bring awareness of how to build adaptive capacities and capabilities in clinicians when working in unpredictable and unanticipated highly pressurised environments.

Learning objectives

To be aware of the current research in safety‐II and the concept of resilience engineering in illustrating the nature of adaptations that happen in complex clinical contexts.

To understand the concept of capability mindfulness, which can help clinicians to focus on their environment and to be alert and aware of correcting errors before they occur.

To be aware of these concepts (behaviour and skills) through the lens of ‘what went well’ in clinicians’ responses to unforeseen and unpredictable situations.
A CONCEPTUAL FRAMEWORK OF DESIGN OPTIMISATION OBJECTIVES FOR ALIGNING LOWER-LIMB EXOSKELETONS TO INDUSTRIAL REVOLUTION 5
Authors: Mahadzir Muhammad Nadzirul Izzat , Halim Isa , Abdullah Zulkeflee , Zainal Abidin Muhammad Zaimi , Saptari Adi
Published: March 2024

Lower-limb exoskeletons can be used extensively in manufacturing, medical, rehabilitation, and the military. The design optimisation for each exoskeleton is vary depending on its intended use. Improving the design of the lower-limb exoskeletons encompasses objectives, attributes, and methods for fulfilling various application. This paper aims to establish a conceptual framework for developing most optimum design for lower-limb exoskeletons for industrial use. Additionally, this paper offers a critical review of design optimization for lower-limb exoskeletons with the aim of enhancing the ergonomics of workers in the industrial sector. To achieve this, this paper delves into an overview of both original research papers and review articles to extract valuable methodologies and design considerations for optimising lower-limb exoskeletons specifically for industrial use. The key outcomes of this paper include recommendedmethods, mechanical design considerations, and a conceptual framework specifically tailored for the design optimization of lower-limb exoskeletons in industrial environments. By offering a comprehensive overview of existing research, this review paper not only aids researchers and designers in the field but also benefits end-users, manufacturers, and the environment. The proposed conceptual framework serves as a valuable tool to guide the development of future lower-limb exoskeletons, ensuring a harmonious integration of technology, user needs, and industrial requirements.
ULASAN SISTEMATIK KEATAS PENGAPLIKASIAN BIOPENDERIA BERASASKAN PERENCATAN ENZIM SEBAGAI KAEDAH SARINGAN AWAL UNTUK PEMANTAUAN ALAM SEKITAR DAN KESELAMATAN MAKANAN
Authors: Sabullah Mohd Khalizan , Abdullah Rahmath , Jawan Roslina , Goh Poh Wah Lucky , Marbawi Hartinie , Syed Najmuddin Syed Umar Faruq , Gansau Jualang Azlan , Syukor Mohd Yunus
Published: March 2024

In this article, the latest discoveries in the development of biosensors based on enzyme inhibition are reviewed. Due to their excellent selectivity and sensitivity, they represent a significant alternative method to conventional analytical methods; which is a method of analysis that only relies on the generation of instrumentation data without any preliminary screening. Basically, biosensors are able to convert biological activity into a quantifiable signal. These enzyme inhibition-based biosensors have a wide range of applications in the fields of environmental safety, food safety, and clinical analysis since toxic substances containing heavy metals and pesticides are the most effective inhibitors of enzymes. This paper is aimed at exploring the methods used and the sensitivity to various inhibitors for biosensors based on the inhibition of enzymes such as glucose oxidase, urease, tyrosinase, cholinesterase, and other enzymes.
EXPERIMENTAL INVESTIGATION ON THE PERFORMANCE EVALUATION OF CONCRETE BINARY BLENDED WITH FLY ASH AND GGBS
Authors: Cheruvu Rajasekhar , Kameswara Rao B
Published: March 2024

It is vital for the sustainability of industry to reduce these emissions while still meeting the ever-increasing demand for infrastructure worldwide. This challenge drew the focus of academics, area experts, and researchers to objectivize their work to investigate alternatives to the cement industry. The present study aims to determine how to reduce the amount of cement by using GGBS and fly ash The study adopted the binder ratios of 0.3,0.4, and 0.5 for both Fly ash and GGBS and compared them with conventional concrete (OPC). Further, the RCPT test examines the durability of the resistance to chloride penetration across different durations, such as 28,56 and 90 days. Also, the sorpitivity test is performed for the above binder ratios to determine the susceptibility of the concrete. The results suggest that the binder ratios adopted for the study have shown better results compared to conventional concrete if the supplementary cementitious materials are restricted to specific percentages.
Right congenital pyriform sinus fistula
Authors: Li Wang , Gao Yihua
Published: March 2024

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Early diagnosis of aspiration pneumonia by gastrointestinal ultrasound combined with lung ultrasound
Authors: Yan Yaru , Zhao Haotian , Yang Chunyan
Published: March 2024

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Temperature-dependent morphology and composition of ultra-thin GeSn epilayers prepared by remote plasma enhanced chemical vapor deposition
Authors: Jiang Jiechao , Chetuya Nonso Martin , Meletis Efstathios I. , Ngai Joseph H. , Grzybowski Gordon J. , Claflin Bruce
Published: March 2024

Two distinct ultra-thin Ge1−xSnx (x ≤ 0.1) epilayers were deposited on (001) Si substrates at 457 and 313 °C through remote plasma-enhanced chemical vapor deposition. These films are considered potential initiation layers for synthesizing thick epitaxial GeSn films. The GeSn film deposited at 313 °C has a thickness of 10 nm and exhibits a highly epitaxial continuous structure with its lattice being compressed along the interface plane to coherently match Si without mismatch dislocations. The GeSn film deposited at 457 °C exhibits a discrete epitaxial island-like morphology with a peak height of ∼30 nm and full-width half maximum (FWHM) varying from 20 to 100 nm. GeSn islands with an FWHM smaller than 20 nm are defect free, whereas those exceeding 25 nm encompass nanotwins and/or stacking faults. The GeSn islands form two-dimensional modulated superlattice structures at the interface with Si. The GeSn film deposited at 457 °C possesses a lower Sn content compared to the one deposited at lower temperature. The potential impact of using these two distinct ultra-thin layers as initiation layers for the direct growth of thicker GeSn epitaxial films on (001) Si substrates is discussed.
Effect of template on the photoresponsivity of BaSi2 films grown on Ge(111) substrates by molecular beam epitaxy
Authors: Aonuki Sho , Takayanagi Kaori , Iwai Ai , Toko Kaoru , Suemasu Takashi
Published: March 2024

Epitaxial growth of BaSi2 films on Si(111) has demonstrated that the BaSi2 template can serve as a seed crystal for BaSi2 overlayers by molecular beam epitaxy (MBE) and shows high photoresponsivity, but not yet on Ge(111) substrates. We have investigated the effect of various templates on the photoresponsivity of BaSi2 films grown on Ge(111) substrates. Samples with MBE-grown templates exhibited high a-axis orientation, but the surface was uneven, leading to partial oxidation of the BaSi2 film. On the other hand, the sample without such templates showed a smoother surface but was confirmed to be polycrystalline. When a template formed by the combination of solid phase epitaxy (SPE) and subsequent annealing for 30 min was used, a-axis-oriented BaSi2 together with 111-oriented Si appeared in the θ–2θ x-ray diffraction (XRD) patterns. The fact that no crystalline Si was detected by the surface-sensitive Raman spectroscopy and that the full width at half maximum of the XRD BaSi2 600 peak was increased to 2.686° in such samples suggests that Si aggregates were at the BaSi2/Ge interface. The photoresponsivity of the epitaxial BaSi2 film with MBE-grown templates reached 0.14 A W−1 at a wavelength of 790 nm. This is the highest photoresponsivity reported so far for BaSi2 films on Ge substrates. Even for samples without the MBE-grown templates, SPE-grown templates significantly increased the photoresponsivity up to 0.10 A W−1. These results confirm that the template has a significant impact on the photoresponsivity of BaSi2 films on Ge(111) substrates.
Strain shift measured from stress-controlled oscillatory shear: Evidence for a continuous yielding transition and new techniques to determine recovery rheology measures
Authors: Griebler James J. , Donley Gavin J. , Wisniewski Victoria , Rogers Simon A.
Published: March 2024

Understanding the yielding of complex fluids is an important rheological challenge that affects our ability to engineer and process materials for a wide variety of applications. Common theoretical understandings of yield stress fluids follow the Oldroyd–Prager formalism in which the material behavior below the yield stress is treated as solidlike, and above the yield stress as liquidlike, with an instantaneous transition between the two states. This formalism was built on a quasi-static approach to the yield stress, while most applications, ranging from material processing to end user applications, involve a transient approach to yielding over a finite timescale. Using stress-controlled oscillatory shear experiments, we show that yield stress fluids flow below their yield stresses. This is quantified through measuring the strain shift, which is the value about which the strain oscillates during a stress-controlled test and is a function of only the unrecoverable strain. Measurements of the strain shift are, therefore, measurements of flow having taken place. These experimental results are compared to the Herschel–Bulkley form of the Saramito model, which utilizes the Oldroyd–Prager formalism, and the recently published Kamani–Donley–Rogers (KDR) model, in which one constitutive equation represents the entire range of material responses. Scaling relationships are derived, which allow us to show why yield stress fluids will flow across all stresses, above and below their yield stress. Finally, derivations are presented that show strain shift can be used to determine average metrics previously attainable only through recovery rheology, and these are experimentally verified.
A Self-Paced Walk Test for Individual Calibration of Heart Rate to Energy Expenditure
Authors: Westgate Kate , Gonzales Tomas I. , Hollidge Stefanie , Lindsay Tim , Wareham Nick , Brage Søren
Published: March 2024

Introduction: Estimating free-living physical activity (PA) with continuous heart rate (HR) monitoring is challenging due to individual variation in the relationship between HR and energy expenditure. This variation can be captured through individual calibration with graded exercise tests, but structured tests with prescribed load require medical screening and are not always feasible in population settings. We present and evaluate an individual calibration method using HR response to a less demanding self-paced walk test. Methods: Six hundred and forty-three participants from the Fenland Study (Cambridgeshire, the United Kingdom) completed a 200-m self-paced walk test, a treadmill test, and 1 week of continuous HR and accelerometry monitoring. Mixed-effects regression was used to derive a walk test calibration model from HR response to the walk using treadmill-based parameters as criterion. Free-living PA estimates from the calibration model were compared with treadmill-calibrated and non-exercise-calibrated estimates. Results: Walk calibration captured 57% of the variance in the HR–energy expenditure relationship determined by the treadmill test. Applying walk calibration to data from free-living yielded similar PA estimates to those using treadmill calibration (52.7 vs. 52.0 kJ·kg−1·day−1; mean difference: 0.7 kJ·kg−1·day−1, 95% confidence interval [−0.0, 1.5]) and high correlation (r = .89). Individual differences were observed (root mean square error: 10.0 kJ·kg−1·day−1; 95% limits of agreement: −20.6, 19.1 kJ·kg−1·day−1). Walk calibration improved precision by 29% compared with nonexercise group calibration (root mean square error: 14.0 kJ·kg−1·day−1; 95% limits of agreement: −30.4, 24.5 kJ·kg−1·day−1). Conclusions: A 200-m self-paced walk test captures between-individual variation in the HR–energy expenditure relationship and facilitates estimation of free-living PA in population settings.
EGFR targeting PhosTACs as a dual inhibitory approach reveals differential downstream signaling
Authors: Hu Zhenyi , Chen Po-Han , Li Wenxue , Krone Mackenzie , Zheng Sijin , Saarbach Jacques , Velasco Ines Urquizo , Hines John , Liu Yansheng , Crews Craig M.
Published: March 2024

We recently developed a heterobifunctional approach [phosphorylation targeting chimeras (PhosTACs)] to achieve the targeted protein dephosphorylation (TPDephos). Here, we envisioned combining the inhibitory effects of receptor tyrosine kinase inhibitors (RTKIs) and the active dephosphorylation by phosphatases to achieve dual inhibition of kinases. We report an example of tyrosine phosphatase–based TPDephos and the effective epidermal growth factor receptor (EGFR) tyrosine dephosphorylation. We also used phosphoproteomic approaches to study the signaling transductions affected by PhosTAC-related molecules at the proteome-wide level. This work demonstrated the differential signaling pathways inhibited by PhosTAC compared with the TKI, gefitinib. Moreover, a covalent PhosTAC selective for mutated EGFR was developed and showed its inhibitory potential for dysregulated EGFR. Last, EGFR PhosTACs, consistent with EGFR dephosphorylation profiles, induced apoptosis and inhibited cancer cell viability during prolonged PhosTAC treatment. PhosTACs showcased their potential of modulating RTKs activity, expanding the scope of bifunctional molecule utility.
Select EZH2 inhibitors enhance viral mimicry effects of DNMT inhibition through a mechanism involving NFAT:AP-1 signaling
Authors: Chomiak Alison A. , Tiedemann Rochelle L. , Liu Yanqing , Kong Xiangqian , Cui Ying , Wiseman Ashley K. , Thurlow Kate E. , Cornett Evan M. , Topper Michael J. , Baylin Stephen B. , Rothbart Scott B.
Published: March 2024

DNA methyltransferase inhibitor (DNMTi) efficacy in solid tumors is limited. Colon cancer cells exposed to DNMTi accumulate lysine-27 trimethylation on histone H3 (H3K27me3). We propose this Enhancer of Zeste Homolog 2 (EZH2)–dependent repressive modification limits DNMTi efficacy. Here, we show that low-dose DNMTi treatment sensitizes colon cancer cells to select EZH2 inhibitors (EZH2is). Integrative epigenomic analysis reveals that DNMTi-induced H3K27me3 accumulates at genomic regions poised with EZH2. Notably, combined EZH2i and DNMTi alters the epigenomic landscape to transcriptionally up-regulate the calcium-induced nuclear factor of activated T cells (NFAT):activating protein 1 (AP-1) signaling pathway. Blocking this pathway limits transcriptional activating effects of these drugs, including transposable element and innate immune response gene expression involved in viral defense. Analysis of primary human colon cancer specimens reveals positive correlations between DNMTi-, innate immune response–, and calcium signaling–associated transcription profiles. Collectively, we show that compensatory EZH2 activity limits DNMTi efficacy in colon cancer and link NFAT:AP-1 signaling to epigenetic therapy–induced viral mimicry.
Enhanced transport of bacteria along root systems by protists can impact plant health
Authors: Micciulla Jamie L. , Shor Leslie M. , Gage Daniel J.
Published: March 2024

Soil protists have been shown to contribute to the structure and function of the rhizosphere in a variety of ways. Protists are key contributors to nutrient cycling through the microbial loop, where biomass is digested by protists and otherwise stored nutrients are returned to the environment. Protists have also been shown to feed on plant pathogenic bacteria and alter root microbiomes in ways that may benefit plants. Recently, a mechanism involving bacterial transport, facilitated by protists, has been hypothesized to contribute to the spatial distribution of bacteria in the rhizosphere. Here, we observe the differential abilities of three soil protists: a ciliate (
Colpoda
sp.), a flagellate (
Cercomonas
sp.), and a naked amoeba (
Acanthamoeba castellanii
) to transport nitrogen-fixing
Sinorhizobium meliloti
to infectible root tips. Co-inoculation of protists plus
S. meliloti
resulted in the movement of bacteria, as measured by the presence of nitrogen-fixing nodules, up to 15 cm farther down the root systems when compared to plants inoculated with
S. meliloti
alone. Co-inoculation of the ciliate
, Colpoda
sp., with
S. meliloti
, resulted in shoot weights that were similar to plants that grew in nitrogen-replete potting mix.
Colpoda
sp.-feeding style and motility likely contributed to their success at transporting bacteria through the rhizosphere. We observed that the addition of protists alone without the co-inoculum of
S. meliloti
resulted in plants with larger shoot weights than control plants. Follow-up experiments showed that protists plus their associated microbiomes were aiding in plant health, likely through means of nutrient cycling.

IMPORTANCE

Protists represent a significant portion of the rhizosphere microbiome and have been shown to contribute to plant health, yet they are understudied compared to their bacterial and fungal counterparts. This study elucidates their role in the rhizosphere community and suggests a mechanism by which protists can be used to move bacteria along plant roots. We found that the co-inoculation of protists with nitrogen-fixing beneficial bacteria,
Sinorhizobium meliloti
, resulted in nodules farther down the roots when compared to plants inoculated with S.
meliloti
alone, and shoot weights similar to plants that received nitrogen fertilizer. These data illustrate the ability of protists to transport viable bacteria to uninhabited regions of the root system.
Proteus mirabilis
UreR coordinates cellular functions required for urease activity
Authors: Fitzgerald Madison J. , Pearson Melanie M. , Mobley Harry L. T.
Published: March 2024

A hallmark of
Proteus mirabilis
infection of the urinary tract is the formation of stones. The ability to induce urinary stone formation requires urease, a nickel metalloenzyme that hydrolyzes urea. This reaction produces ammonia as a byproduct, which can serve as a nitrogen source and weak base that raises the local pH. The resulting alkalinity induces the precipitation of ions to form stones. Transcriptional regulator UreR activates expression of urease genes in a urea-dependent manner. Thus, urease genes are highly expressed in the urinary tract where urea is abundant. Production of mature urease also requires the import of nickel into the cytoplasm and its incorporation into the urease apoenzyme. Urease accessory proteins primarily acquire nickel from one of two nickel transporters and facilitate incorporation of nickel to form mature urease. In this study, we performed a comprehensive RNA-seq to define the
P. mirabilis
urea-induced transcriptome as well as the UreR regulon. We identified UreR as the first defined regulator of nickel transport in
P. mirabilis
. We also offer evidence for the direct regulation of the Ynt nickel transporter by UreR. Using bioinformatics, we identified UreR-regulated urease loci in 15
Morganellaceae
family species across three genera. Additionally, we located two mobilized UreR-regulated urease loci that also encode the
ynt
transporter, implying that UreR regulation of nickel transport is a conserved regulatory relationship. Our study demonstrates that UreR specifically regulates genes required to produce mature urease, an essential virulence factor for
P. mirabilis
uropathogenesis.

IMPORTANCE

Catheter-associated urinary tract infections (CAUTIs) account for over 40% of acute nosocomial infections in the USA and generate $340 million in healthcare costs annually. A major causative agent of CAUTIs is
Proteus mirabilis
, an understudied Gram-negative pathogen noted for its ability to form urinary stones via the activity of urease. Urease mutants cannot induce stones and are attenuated in a murine UTI model, indicating this enzyme is essential to
P. mirabilis
pathogenesis. Transcriptional regulation of urease genes by UreR is well established; here, we expand the UreR regulon to include regulation of nickel import, a function required to produce mature urease. Furthermore, we reflect on the role of urea catalysis in
P. mirabilis
metabolism and provide evidence for its importance.
Enrichable consortia of microbial symbionts degrade macroalgal polysaccharides in
Kyphosus
fish
Authors: Oliver Aaron , Podell Sheila , Wegley Kelly Linda , Sparagon Wesley J. , Plominsky Alvaro M. , Nelson Robert S. , Laurens Lieve M. L. , Augyte Simona , Sims Neil A. , Nelson Craig E. , Allen Eric E.
Published: March 2024

Coastal herbivorous fishes consume macroalgae, which is then degraded by microbes along their digestive tract. However, there is scarce genomic information about the microbiota that perform this degradation. This study explores the potential of
Kyphosus
gastrointestinal microbial symbionts to collaboratively degrade and ferment polysaccharides from red, green, and brown macroalgae through
in silico
study of carbohydrate-active enzyme and sulfatase sequences. Recovery of metagenome-assembled genomes (MAGs) from previously described
Kyphosus
gut metagenomes and newly sequenced bioreactor enrichments reveals differences in enzymatic capabilities between the major microbial taxa in
Kyphosus
guts. The most versatile of the recovered MAGs were from the
Bacteroidota
phylum, whose MAGs house enzyme collections able to decompose a variety of algal polysaccharides. Unique enzymes and predicted degradative capacities of genomes from the
Bacillota
(genus
Vallitalea
) and
Verrucomicrobiota
(order
Kiritimatiellales
) highlight the importance of metabolic contributions from multiple phyla to broaden polysaccharide degradation capabilities. Few genomes contain the required enzymes to fully degrade any complex sulfated algal polysaccharide alone. The distribution of suitable enzymes between MAGs originating from different taxa, along with the widespread detection of signal peptides in candidate enzymes, is consistent with cooperative extracellular degradation of these carbohydrates. This study leverages genomic evidence to reveal an untapped diversity at the enzyme and strain level among
Kyphosus
symbionts and their contributions to macroalgae decomposition. Bioreactor enrichments provide a genomic foundation for degradative and fermentative processes central to translating the knowledge gained from this system to the aquaculture and bioenergy sectors.

IMPORTANCE

Seaweed has long been considered a promising source of sustainable biomass for bioenergy and aquaculture feed, but scalable industrial methods for decomposing terrestrial compounds can struggle to break down seaweed polysaccharides efficiently due to their unique sulfated structures. Fish of the genus
Kyphosus
feed on seaweed by leveraging gastrointestinal bacteria to degrade algal polysaccharides into simple sugars. This study reconstructs metagenome-assembled genomes for these gastrointestinal bacteria to enhance our understanding of herbivorous fish digestion and fermentation of algal sugars. Investigations at the gene level identify
Kyphosus
guts as an untapped source of seaweed-degrading enzymes ripe for further characterization. These discoveries set the stage for future work incorporating marine enzymes and microbial communities in the industrial degradation of algal polysaccharides.
SARS-CoV-2 pandemic non-pharmacologic interventions temporally associated with reduced pediatric infections due to
Mycoplasma pneumoniae
and co-infecting respiratory viruses in Arkansas
Authors: Boyanton Bobby L. , Frenner Rachel A. , Ingold Ashton , Ambroggio Lilliam , Kennedy Joshua L.
Published: March 2024

Non-pharmacologic interventions (NPIs), such as universal masking, implemented during the SARS-CoV-2 pandemic have reduced respiratory infections among children. This study evaluated the impact of NPIs on
Mycoplasma pneumoniae
infections in children, analyzing data from two hospitals in Arkansas and examining age-related differences and co-infections with other respiratory viruses. The study was approved by the Institutional Review Board and included patients (≤18 years) with upper respiratory tract symptoms. Data generated from the FilmArray Respiratory Panel were divided into pre-NPI, NPI, and post-NPI periods for analysis. Overall test positivity rate and positivity rate interval changes were evaluated. Statistical differences were determined by Chi-square (χ
2
independence) analysis. A total of 100,077 tests were performed, with a statistical increase in testing volume during the NPI and post-NPI periods. The number of positive
M. pneumoniae
tests decreased by 77% (77 to 18) during the NPI period, then increased by 50% (18 to 27) during the post-NPI period. Preschool and elementary school age groups had the highest number of positive tests during the study at 59 (48%) and 40 (33%), respectively. Reduced
M. pneumoniae
infections were consistent across age groups. Co-infections with other respiratory viruses, particularly human rhinovirus/enterovirus, were observed at much lower levels. Pediatric
M. pneumoniae
infections in Arkansas were temporally associated with implementation and discontinuation of NPIs. Specific viral co-infections still occurred, albeit at lower levels during the SARS-CoV-2 pandemic. Because of the slower growth of this bacterium, we expect
M. pneumoniae
infections to return to pre-pandemic levels within approximately 2 years.

IMPORTANCE

Non-pharmacologic interventions (NPIs) effectively curtailed the spread of SARS-CoV-2 and, fortuitously, many other aerosol-transmitted respiratory pathogens. This study included the largest data set of symptomatic, pediatric patients from within the United States spanning a period from November 2017 through December 2023, and encompassed individuals residing in both rural and urban settings. We observed a strong correlation between the implementation and cessation of NPIs with the rate of respiratory infections due to
Mycoplasma pneumoniae
and viral co-infections. These infections are returning to baseline levels approximately 2 years following NPI cessation. This observation was not unexpected since the replication time for viruses is exponentially faster than that of bacteria. The resurgence of
M. pneumoniae
and likely other atypical bacterial pathogens is currently in process. Healthcare providers should strongly consider these pathogens in individuals presenting with respiratory tract illnesses.