bluuebunny/crossref_metadata_2025_split huggingface dataset:
Agrin/Lrp4 signal constrains MuSK-dependent neuromuscular synapse development in appendicular muscle
Authors: Walker Lauren J. , Roque Rebecca A. , Navarro Maria F. , Granato Michael 
Published: October 2021

ABSTRACT
The receptor tyrosine kinase MuSK, its co-receptor Lrp4 and the Agrin ligand constitute a signaling pathway that is crucial in axial muscle for neuromuscular synapse development, yet whether this pathway functions similarly in appendicular muscle is unclear. Here, using the larval zebrafish pectoral fin, equivalent to tetrapod forelimbs, we show that, similar to axial muscle, developing appendicular muscles form aneural acetylcholine receptor (AChR) clusters prior to innervation. As motor axons arrive, neural AChR clusters form, eventually leading to functional synapses in a MuSK-dependent manner. We find that loss of Agrin or Lrp4 function, which abolishes synaptic AChR clusters in axial muscle, results in enlarged presynaptic nerve regions and progressively expanding appendicular AChR clusters, mimicking the consequences of motoneuron ablation. Moreover, musk depletion in lrp4 mutants partially restores synaptic AChR patterning. Combined, our results provide compelling evidence that, in addition to the canonical pathway in which Agrin/Lrp4 stimulates MuSK activity, Agrin/Lrp4 signaling in appendicular muscle constrains MuSK-dependent neuromuscular synapse organization. Thus, we reveal a previously unappreciated role for Agrin/Lrp4 signaling, thereby highlighting distinct differences between axial and appendicular synapse development.
Infant leukaemia – faithful models, cell of origin and the niche
Authors: Duguid Alasdair , Mattiucci Domenico , Ottersbach Katrin 
Published: October 2021

ABSTRACT
For patients and their families, the diagnosis of infant leukaemia is devastating. This disease has not seen the improvements in outcomes experienced with other paediatric leukaemias and it is becoming ever more apparent that infant leukaemia is a distinct biological entity. Insights into some of the distinguishing features of infant leukaemia, such as a single mutation – the MLL-gene rearrangement, the biology of disease aggressiveness and lineage plasticity, and the high incidence of central nervous system involvement, are likely to be gained from understanding the interactions between leukaemic cells and their environment or niche. The origins of infant leukaemia lie in the embryonic haematopoietic system, which is characterised by shifting locations and dynamic changes in the microenvironment. Understanding this foetal or embryonic context is integral to understanding infant leukaemia development. Owing to its rarity and prenatal origins, developing accurate modelling systems for further investigation of infant leukaemia is essential. In this Review, we discuss how available in vitro, ex vivo and in vivo infant leukaemia models contribute to our current understanding of the leukaemia niche in embryonic development, established disease and specialised non-haematopoietic niches. The mechanistic insights provided by accurate models will help identify viable novel therapeutic options.
Nuclear import of BCL11B is mediated by a classical nuclear localization signal and not the Krüppel-like zinc fingers
Authors: Grabarczyk Piotr , Delin Martin , Rogińska Dorota , Schulig Lukas , Forkel Hannes , Depke Maren , Link Andreas , Machaliński Bogusław , Schmidt Christian Andreas 
Published: October 2021

ABSTRACT
The Krüppel-like transcription factor (KLF) BCL11B is characterized by a wide tissue distribution and crucial functions in key developmental and cellular processes, as well as in various pathologies including cancer and HIV infection. Although the basics of BCL11B activity and relevant interactions with other proteins have been uncovered, how this exclusively nuclear protein localizes to its compartment remained unclear. Here, we demonstrate that unlike other KLFs, BCL11B does not require the C-terminal DNA-binding domain to pass through the nuclear envelope but has an independent, previously unidentified, nuclear localization signal (NLS), which is located distantly from the zinc finger domains and fulfills the essential criteria of being an autonomous NLS. First, it can redirect a heterologous cytoplasmic protein to the nucleus. Second, its mutation causes aberrant localization of the protein of origin. Finally, we provide experimental and in silico evidences of the direct interaction with importin-α. The relative conservation of this motif allows formulating a consensus sequence (K/R)K-X13–14-KR+K++ (‘+’ indicates amino acids with similar chemical properties), which can be found in all BCL11B orthologs among vertebrates and in the closely related protein BCL11A.
Rapid embryonic development supports the early onset of gill functions in two coral reef damselfishes
Authors: Prescott Leteisha A. , Regish Amy M. , McMahon Shannon J. , McCormick Stephen D. , Rummer Jodie L. 
Published: October 2021

ABSTRACTThe gill is one of the most important organs for growth and survival of fishes. Early life stages in coral reef fishes often exhibit extreme physiological and demographic characteristics that are linked to well-established respiratory and ionoregulatory processes. However, gill development and function in coral reef fishes is not well understood. Therefore, we investigated gill morphology, oxygen uptake and ionoregulatory systems throughout embryogenesis in two coral reef damselfishes, Acanthochromis polyacanthus and Amphiprion melanopus (Pomacentridae). In both species, we found key gill structures to develop rapidly early in the embryonic phase. Ionoregulatory cells appear on gill filaments 3–4 days post-fertilization and increase in density, whilst disappearing or shrinking in cutaneous locations. Primary respiratory tissue (lamellae) appears 5–7 days post-fertilization, coinciding with a peak in oxygen uptake rates of the developing embryos. Oxygen uptake was unaffected by phenylhydrazine across all ages (pre-hatching), indicating that haemoglobin is not yet required for oxygen uptake. This suggests that gills have limited contribution to respiratory functions during embryonic development, at least until hatching. Rapid gill development in damselfishes, when compared with that in most previously investigated fishes, may reflect preparations for a high-performance, challenging lifestyle on tropical reefs, but may also make reef fishes more vulnerable to anthropogenic stressors.
Influence of Age and Estradiol on Sympathetic Nerve Activity Responses to Exercise in Women
Authors: WENNER MEGAN M. , GREANEY JODY L. , MATTHEWS EVAN L. , MCGINTY SHANE , KAUR JASDEEP , VONGPATANASIN WANPEN , FADEL PAUL J. 
Published: October 2021

ABSTRACT

Introduction
Postmenopausal women (PMW) display exaggerated increases in blood pressure (BP) during exercise, yet the mechanism(s) involved remain unclear. Moreover, research on the impact of menopausal changes in estradiol on cardiovascular control during exercise are limited. Herein, we tested the hypothesis that sympathetic responses during exercise are augmented in PMWcompared with young women (YW), and estradiol administration attenuates these responses.

Methods
Muscle sympathetic nerve activity (MSNA) and mean arterial pressure (MAP) were measured in 13 PMW (58 ± 1 yr) and 17 YW (22 ± 1 yr) during 2 min of isometric handgrip. Separately, MSNA and BP responses were measured during isometric handgrip in six PMW (53 ± 1 yr) before and after 1 month of transdermal estradiol (100 μg·d−1). A period of postexercise ischemia (PEI) to isolate muscle metaboreflex activation followed all handgrip bouts.

Results
Resting MAP was similar between PMW and YW, whereas MSNA was greater in PMW (23 ± 3 vs 8 ± 1 bursts per minute; P < 0.05). During handgrip, the increases in MSNA (PMW Δ16 ± 2 vs YW Δ6 ± 1 bursts per minute; P < 0.05) and MAP (PMW Δ18 ± 2 vs YW Δ12 ± 2 mm Hg; P < 0.05) were greater in PMW and remained augmented during PEI. Estradiol administration decreased resting MAP but not MSNA in PMW. Moreover, MSNA (PMW (−E2) Δ27 ± 8 bursts per minute versus PMW (+E2) Δ12 ± 5 bursts per minute; P < 0.05) and MAP (Δ31 ± 8 mm Hg vs Δ20 ± 6 mm Hg; P < 0.05) responses during handgrip were attenuated in PMW after estradiol administration. Likewise, MAP responses during PEI were lower after estradiol.

Conclusions
These data suggest that PMW exhibit an exaggerated MSNA and BP response to isometric exercise, due in part to heightened metaboreflex activation. Furthermore, estradiol administration attenuated BP and MSNA responses to exercise in PMW.
A novel e-learning tool to improve knowledge and awareness of pelvic radiotherapy late effects: qualitative responses amongst therapeutic radiographers
Authors: Oliver Lauren Ann , Porritt Bridget , Kirby Mike 
Published: October 2021

Objectives: This study aimed to investigate the effectiveness of a novel e-learning intervention to increase knowledge, awareness and confidence surrounding pelvic radiotherapy late effects amongst therapeutic radiographers (RTTs), and to change staff perceptions of responsibility in providing such information to patients. Methods: The e-learning intervention was developed using blended learning software (Articulate Global, New York). 23 therapeutic radiographers within a single UK radiotherapy institution received the e-learning. Semi-structured interviews and questionnaires were utilised pre- and post-intervention to obtain qualitative and quantitative results. Thematic analysis of coded interview responses identified recurring themes, whilst statistical analysis was conducted using a Wilcoxon signed-rank test. This first paper presents the qualitative results. Results: Thematic analysis revealed increased knowledge and awareness of pelvic radiotherapy late effects amongst participants. Five key themes were identified: Knowledge/Confidence; Consent; Professional Responsibility; Gaps within Practice and Time/Space. Whilst several staff reported increased confidence in discussing late effects with patients, further training utilising “blended” pedagogical approaches may be required to achieve longstanding improvements. Following e-learning, participants demonstrated increased professional responsibility to deliver late effects information to patients. Conclusion: The novel e-learning intervention increased staff knowledge, awareness and confidence surrounding pelvic radiotherapy late effects, whilst changing staff perceptions on professional responsibility in delivering such information. Advances in knowledge: The e-learning has been disseminated to all hospitals within the region including a new “Radiotherapy Late Effects Clinic”, educating various healthcare professionals. Study recommendations have led to introduction of dedicated radiotherapy late effects modules on a novel MSc programme at a UK University.
A simple and cheap aerosol penetrometer for filter testing using an electronic cigarette.
Authors: Lifka Sebastian , Ponomarev Ivan , Weth Agnes , Baumgartner David , Lamprecht Bernd , Baumgartner Werner 
Published: October 2021

Background: During the coronavirus disease 2019 (COVID-19) pandemic face masks grew in importance as their use by the general population was recommended by health officials in order to minimize the risk of infection and prevent further spread of the virus. To ensure health protection of medical personnel and other system relevant staff, it is of considerable interest to quickly test if a certain lot of filtering facepiece masks meets the requirements or if the penetration changes under different conditions. As certified penetrometers are rather expensive and were difficult to obtain during the COVID-19 pandemic, we describe two quite simple and cheap methods to quickly test the filter penetration based on an electronic cigarette. Methods: The first method uses a precision scale, the second method uses a light scattering detector to measure the filter penetration. To make sure these two methods yield reliable results, both were tested with freshly cut filter samples covering the range of approx. 2 % to 60 % filter penetration and compared to the results of a certified penetrometer. Results: The comparison of the two methods with the certified penetrometer showed a good correlation and therefore allow a quick and rather reliable estimation of the penetration. Conclusions: Several examples about the use of faulty masks and the resulting health risks show that simple, fast, cheap and broadly available methods for filter characterization might be useful in these days.
Does the Potential to Merge Reduce Competition?
Authors: Hackbarth Dirk , Taub Bart 
Published: October 2021

We study anticompetitive horizontal mergers in a dynamic model with noisy collusion. At each instant, firms either privately choose output levels or merge to form a monopoly, trading off the benefits of avoiding price wars against the costs of merging. The potential to merge decreases pre-merger collusion, as punishments effected by price wars are weakened. We thus extend the result of Davidson and Deneckere [Davidson C, Deneckere R (1984) Horizontal mergers and collusive behavior. Internat. J. Indust. Organ. 2(2):117–132.], who analyzed the weakening of punishments post-merger, demonstrating that pre-merger collusion is weakened, in a fully stochastic model. Thus, although anticompetitive mergers harm competition ex post, the implication is that barriers and costs of merging due to regulation should be reduced to promote competition exante. This paper was accepted by Tomasz Piskorski, finance.
Work readiness in rehabilitation medicine: a qualitative exploration and framework
Authors: Suleman Salima , Hall Mark , Bostick Geoffrey , Paslawski Teresa , Schmitz Cori , McFarlane Lu-Anne 
Published: October 2021

Background/aims The skills and attributes that facilitate the transition from student to professional (also known as work readiness) have not been fully explored in rehabilitation medicine. The aim of this study was to develop a model of work readiness for new rehabilitation medicine professionals that allows for a successful transition to the workplace. Methods A qualitative approach was used to explore the perspectives of 26 clinicians, regulators and employers about work readiness in rehabilitation disciplines. Transcripts were coded and analysed using content analysis methods. Results At the core of work readiness for rehabilitation medicine professionals were three complex endeavours that were framed as professional challenges. Each endeavour integrated one or more foundational skills and could improve context-bound applied skills. Conclusions Work readiness in rehabilitation requires active and ongoing commitment from students, post-secondary programmes and employers.
Understanding brokers, intermediaries, and boundary spanners: a multi-sectoral review of strategies, skills, and outcomes
Authors: Neal Jennifer Watling , Posner Stephen , Brutzman Brian 
Published: October 2021

Background:Brokers, intermediaries, and boundary spanners (BIBS) bridge research and policy or practice, and can elevate the role of evidence in decision making. However, there is limited integration of the literature across different sectors to understand the strategies that BIBS use, the skills needed to carry out these strategies, and the expected outcomes of these strategies.
Aims and objectives:In this review, we characterise the strategies, skills, and outcomes of BIBS across the literature in education, environmental, health and other relevant sectors.
Methods:We included 185 conceptual and review papers written in English that included descriptions or conceptualisations of BIBS in the context of knowledge transfer or research use in the education, environmental, health, or other relevant sectors (for example, social services, international development). For each included paper, we extracted and coded information on sector, BIBS strategies, skills, and outcomes.
Findings:Our review revealed five strategies used by BIBS that were emphasised in the literature. Specifically, 79.5% of papers mentioned facilitating relationships, 75.7% mentioned disseminating evidence, 56.8% mentioned finding alignment, 48.6% mentioned capacity building, and 37.3% mentioned advising decisions as strategies used by BIBS. Additionally, papers described skills and expected outcomes that were common across these strategies as well as those that were unique to specific strategies.
Discussion and conclusions:We discuss implications of these findings for understanding how BIBS interface with knowledge users and producers as well as directions for future research on BIBS and the professionalisation of BIBS roles.
High-speed multiview imaging approaching 4pi steradians using conic section mirrors: theoretical and practical considerations
Authors: Zhou Kevin C. , Dhalla Al-Hafeez , McNabb Ryan P. , Qian Ruobing , Farsiu Sina , Izatt Joseph A. 
Published: October 2021

Illuminating or imaging samples from a broad angular range is essential in a wide variety of computational 3D imaging and resolution-enhancement techniques, such as optical projection tomography, optical diffraction tomography, synthetic aperture microscopy, Fourier ptychographic microscopy, structured illumination microscopy, photogrammetry, and optical coherence refraction tomography. The wider the angular coverage, the better the resolution enhancement or 3D-resolving capabilities. However, achieving such angular ranges is a practical challenge, especially when approaching±90∘or beyond. Often, researchers resort to expensive, proprietary high numerical aperture (NA) objectives or to rotating the sample or source-detector pair, which sacrifices temporal resolution or perturbs the sample. Here, we propose several new strategies for multiangle imaging approaching 4pi steradians using concave parabolic or ellipsoidal mirrors and fast, low rotational inertia scanners, such as galvanometers. We derive theoretically and empirically relations between a variety of system parameters (e.g., NA, wavelength, focal length, telecentricity) and achievable fields of view (FOVs) and importantly show that intrinsic tilt aberrations donotrestrict FOV for many multiview imaging applications, contrary to conventional wisdom. Finally, we present strategies for avoiding spherical aberrations at obliquely illuminated flat boundaries. Our simple designs allow for high-speed multiangle imaging for microscopic, mesoscopic, and macroscopic applications.
Widely wavelength tunable Dy3+/Er3+ co-doped ZBLAN fiber lasers
Authors: Wang Junfeng , Zhu Xiushan , Norwood Robert A. , Peyghambarian Nasser 
Published: October 2021

Wavelength tunable dysprosium-erbium (Dy3+/Er3+) co-doped ZBLAN (ZrF4-BaF2-LaF3-AlF3-NaF) fiber lasers pumped at 980 nm were developed with a bulk grating blazed at 3.1 µm in the Littrow configuration and their performances were investigated. A wavelength tunable range of 674.4 nm (2709.2 nm −3373.6 nm) was achieved with a 4.5-m 0.25 mol.% Dy3+/ 4 mol.% Er3+ co-doped ZBLAN fiber. Our experiments demonstrated that either Er3+ or Dy3+ can be lasing individually in a Dy3+/Er3+ co-doped ZBLAN fiber and a fiber laser with wavelength tunable range from 2.7 µm to 3.4 µm or longer wavelengths can be achieved with proper fiber and cavity design.
„Sie werden eh einen Weg finden, um es zu umgehen“ – Ein führender Automobilhersteller kämpft mit Datensicherheit in der Neuproduktentwicklung
Authors: Weber Ramona , Gernreich Chris C. , Wolf Verena 
Published: October 2021

ZusammenfassungWährend sich Unternehmen die Möglichkeiten der vernetzten Informations- und Kommunikationstechnologie für die gemeinsame Entwicklung neuer Produkte zunutze machen, stellen sich gleichzeitig Fragen nach dem Schutz von vertraulichen Informationen und Wissen. Um ihre ungewollte Verbreitung zu vermeiden, benötigen Unternehmen in verschiedenen Branchen klare Strategien zur Risikominimierung. Durch den aktuellen Wandel hin zur Elektromobilität herrscht in der Automobilindustrie ein harter Wettbewerb und die Gefahr von Nachahmung ist groß. Wir präsentieren eine explorative Fallstudie in einem führenden europäischen Automobilunternehmen und untersuchen das Verhalten am Arbeitsplatz und die damit verbundenen Informationssicherheit bei der Entwicklung neuer Produkte. Die Ergebnisse zeigen, dass das Bewusstsein zum Schutz von Informationen in Organisationsroutinen verwurzelt ist und dass bestehende Sicherheitsmaßnahmen eine schwache Wirkung haben. Unpraktische formale Sicherheitsrichtlinien sowie hierarchische Spannungen und Zeitdruck führen zu riskanten Verhaltensweisen der Mitarbeiter. Unsere Ergebnisse weisen auf die Bedeutung von Transparenz und Flexibilität von Wissenssicherheitsrichtlinien hin. Darüber hinaus bieten wir eine neue Perspektive auf den Wissenstransfer, indem wir die sog. Sichtbarkeitslinie für Informationen einführen und einen Sicherheitsrahmen für die Praxis vorstellen.
Exhaled nitric oxide detection for diagnosis of COVID-19 in critically ill patients
Authors: Exline Matthew C. , Stanacevic Milutin , Bowman Andrew S. , Gouma Pelagia-Irene 
Published: October 2021

BackgroundCOVID-19 may present with a variety of clinical syndromes, however, the upper airway and the lower respiratory tract are the principle sites of infection. Previous work on respiratory viral infections demonstrated that airway inflammation results in the release of volatile organic compounds as well as nitric oxide. The detection of these gases from patients’ exhaled breath offers a novel potential diagnostic target for COVID-19 that would offer real-time screening of patients for COVID-19 infection.Methods and findingsWe present here a breath tester utilizing a catalytically active material, which allows for the temporal manifestation of the gaseous biomarkers’ interactions with the sensor, thus giving adistinct breath printof the disease. A total of 46 Intensive Care Unit (ICU) patients on mechanical ventilation participated in the study, 23 with active COVID-19 respiratory infection and 23 non-COVID-19 controls. Exhaled breath bags were collected on ICU days 1, 3, 7, and 10 or until liberation from mechanical ventilation. The breathalyzer detected high exhaled nitric oxide (NO) concentration with a distinctive pattern for patients with active COVID-19 pneumonia. The COVID-19 “breath print” has the pattern of the small Greek letter omega (). The “breath print” identified patients with COVID-19 pneumonia with 88% accuracy upon their admission to the ICU. Furthermore, the sensitivity index of the breath print (which scales with the concentration of the key biomarker ammonia) appears to correlate with duration of COVID-19 infection.ConclusionsThe implication of this breath tester technology for the rapid screening for COVID-19 and potentially detection of other infectious diseases in the future.