bluuebunny/crossref_metadata_2025 huggingface dataset:
Doped iron oxide scaffolds with gradient porosity fabricated by freeze casting: Pore morphology prediction and processing parameters
Authors: Lloreda-Jurado P. J. , Pérez-Soriano E. M. , Paúl A. , Herguido J. , Peña J. A. , Sepúlveda R.
Published: May 2020

Iron oxide scaffolds with gradient porosity were fabricated using the freeze-casting technique. Doped iron oxide particles were employed to generate stable particle suspensions in camphene using the ball-milling technique. Viscosity measurements were performed to determine the effect of the milling time and the additive incorporation. The freeze-casting process implemented in this work created a wide diversity of solidification front velocities, [Formula: see text] (2–80 µm s−1), and thermal gradients,[Formula: see text] (0.2–20°C cm−1) during sample fabrication. The solidification problem of liquid/solid systems has often been reviewed, but usually only under steady-state conditions. This study presents a much simpler approach for the correlation of the average dendrite arm spacing [Formula: see text] and pore morphology with different processing parameters.

GRAPHICAL ABSTRACT
The characteristic smell emitted from two scale insects, Ceroplastes japonicus and Ceroplastes rubens
Authors: Sakurai Kazutoshi , Tomiyama Kenichi , Yaguchi Yoshihiro , Asakawa Yoshinori
Published: May 2020

The volatile components emitted from two scale insects, Ceroplastes japonicus and Ceroplastes rubens, were identified using GC–MS analysis. The major volatile components of the solvent extract from C. japonicus were α-humulene (35.8%) and δ-cadinene (17.0%), while those of C. rubens were β-selinene (10.3%) and β-elemene (5.1%). In GC/olfactometry, linalool, butyric acid, 3-methylbutyric acid, 2-methylbutyric acid, and vanillin were identified as the odor-active components of the extract from C. japonicus, in addition to trace amounts of trans-4,5-epoxy-(2E)-decenal, 4-methyl-(3E)-hexenoic acid, and phenylacetic acid. With regard to C. rubens, trans-4,5-epoxy-(2E)-decenal, 3-methylbutyric acid, and phenylacetic acid were identified as the odor-active components. Besides, decan-1,4-olide (γ-decalactone) with milky cherry-like note and 3-hydroxy-4,5-dimethylfuran-2(5H)-one (sotolone) with brown sugar-like note were also detected as the characteristic cherry-like sweet-and-sour note of these two scale insects.

Abbreviations

GC: Gas chromatography; GC/O: gas chromatography/olfactometry
Fission yeast Pak1 phosphorylates anillin-like Mid1 for spatial control of cytokinesis
Authors: Magliozzi Joseph O. , Sears Jack , Cressey Lauren , Brady Marielle , Opalko Hannah E. , Kettenbach Arminja N. , Moseley James B.
Published: May 2020

Protein kinases direct polarized growth by regulating the cytoskeleton in time and space and could play similar roles in cell division. We found that the Cdc42-activated polarity kinase Pak1 colocalizes with the assembling contractile actomyosin ring (CAR) and remains at the division site during septation. Mutations in pak1 led to defects in CAR assembly and genetic interactions with cytokinesis mutants. Through a phosphoproteomic screen, we identified novel Pak1 substrates that function in polarized growth and cytokinesis. For cytokinesis, we found that Pak1 regulates the localization of its substrates Mid1 and Cdc15 to the CAR. Mechanistically, Pak1 phosphorylates the Mid1 N-terminus to promote its association with cortical nodes that act as CAR precursors. Defects in Pak1-Mid1 signaling lead to misplaced and defective division planes, but these phenotypes can be rescued by synthetic tethering of Mid1 to cortical nodes. Our work defines a new signaling mechanism driven by a cell polarity kinase that promotes CAR assembly in the correct time and place.
Calcineurin-dependent regulation of endocytosis by a plasma membrane ubiquitin ligase adaptor, Rcr1
Authors: Zhu Lu , Sardana Richa , Jin Daniel K. , Emr Scott D.
Published: May 2020

Rsp5, the Nedd4 family member in yeast, is an E3 ubiquitin ligase involved in numerous cellular processes, many of which require Rsp5 to interact with PY-motif containing adaptor proteins. Here, we show that two paralogous transmembrane Rsp5 adaptors, Rcr1 and Rcr2, are sorted to distinct cellular locations: Rcr1 is a plasma membrane (PM) protein, whereas Rcr2 is sorted to the vacuole. Rcr2 is delivered to the vacuole using ubiquitin as a sorting signal. Rcr1 is delivered to the PM by the exomer complex using a newly uncovered PM sorting motif. Further, we show that Rcr1, but not Rcr2, is up-regulated via the calcineurin/Crz1 signaling pathway. Upon exogenous calcium treatment, Rcr1 ubiquitinates and down-regulates the chitin synthase Chs3. We propose that the PM-anchored Rsp5/Rcr1 ubiquitin ligase-adaptor complex can provide an acute response to degrade unwanted proteins under stress conditions, thereby maintaining cell integrity.
Fam20C regulates protein secretion by Cab45 phosphorylation
Authors: Hecht Tobias Karl-Heinz , Blank Birgit , Steger Martin , Lopez Victor , Beck Gisela , Ramazanov Bulat , Mann Matthias , Tagliabracci Vincent , von Blume Julia
Published: May 2020

The TGN is a key compartment for the sorting and secretion of newly synthesized proteins. At the TGN, soluble proteins are sorted based on the instructions carried in their oligosaccharide backbones or by a Ca2+-mediated process that involves the cargo-sorting protein Cab45. Here, we show that Cab45 is phosphorylated by the Golgi-specific protein kinase Fam20C. Mimicking of phosphorylation translocates Cab45 into TGN-derived vesicles, which goes along with an increased export of LyzC, a Cab45 client. Our findings demonstrate that Fam20C plays a key role in the export of Cab45 clients by fine-tuning Cab45 oligomerization and thus impacts Cab45 retention in the TGN.
Single-cell temperature mapping with fluorescent thermometer nanosheets
Authors: Oyama Kotaro , Gotoh Mizuho , Hosaka Yuji , Oyama Tomoko G. , Kubonoya Aya , Suzuki Yuma , Arai Tomomi , Tsukamoto Seiichi , Kawamura Yuki , Itoh Hideki , Shintani Seine A. , Yamazawa Toshiko , Taguchi Mitsumasa , Ishiwata Shin’ichi , Fukuda Norio
Published: May 2020

Recent studies using intracellular thermometers have shown that the temperature inside cultured single cells varies heterogeneously on the order of 1°C. However, the reliability of intracellular thermometry has been challenged both experimentally and theoretically because it is, in principle, exceedingly difficult to exclude the effects of nonthermal factors on the thermometers. To accurately measure cellular temperatures from outside of cells, we developed novel thermometry with fluorescent thermometer nanosheets, allowing for noninvasive global temperature mapping of cultured single cells. Various types of cells, i.e., HeLa/HEK293 cells, brown adipocytes, cardiomyocytes, and neurons, were cultured on nanosheets containing the temperature-sensitive fluorescent dye europium (III) thenoyltrifluoroacetonate trihydrate. First, we found that the difference in temperature on the nanosheet between nonexcitable HeLa/HEK293 cells and the culture medium was less than 0.2°C. The expression of mutated type 1 ryanodine receptors (R164C or Y523S) in HEK293 cells that cause Ca2+ leak from the endoplasmic reticulum did not change the cellular temperature greater than 0.1°C. Yet intracellular thermometry detected an increase in temperature of greater than ∼2°C at the endoplasmic reticulum in HeLa cells upon ionomycin-induced intracellular Ca2+ burst; global cellular temperature remained nearly constant within ±0.2°C. When rat neonatal cardiomyocytes or brown adipocytes were stimulated by a mitochondrial uncoupling reagent, the temperature was nearly unchanged within ±0.1°C. In cardiomyocytes, the temperature was stable within ±0.01°C during contractions when electrically stimulated at 2 Hz. Similarly, when rat hippocampal neurons were electrically stimulated at 0.25 Hz, the temperature was stable within ±0.03°C. The present findings with nonexcitable and excitable cells demonstrate that heat produced upon activation in single cells does not uniformly increase cellular temperature on a global basis, but merely forms a local temperature gradient on the order of ∼1°C just proximal to a heat source, such as the endoplasmic/sarcoplasmic reticulum ATPase.
Final report on supplementary regional comparison SIM.AUV.A-S2: calibration of pistonphone
Authors: Milhomem T A B , Soares Z M D , Ripper G P , Ayala J P , Guevara G M , Serrano F A , Solano A , Wagner R P , Hanes P
Published: May 2020

This document is the Final Report of the Inter-American Metrology System supplementary comparison on pistonphone calibration SIM.AUV.A-S2. Seven national metrology institutes participated on this comparison: CENAM/Mexico, INACAL/Peru, INMETRO/Brazil, INTI/Argentina, LACOMET/Costa Rica, NIST/USA and NRC/Canada and INMETRO was the pilot institute responsible for its coordination. One pistonphone was circulated among the participants to carry out calibrations according to the international standard IEC 60942:2017 using both LS1P and LS2P measurement microphones. Beyond the mandatory measurement of the sound pressure level, it was requested to the participants report measurement results of frequency, total harmonic distortion and total distortion + noise for the purpose of investigation. For sound pressure level and frequency measurement results, supplementary comparison reference values (SCRVs) were determined using the weighted mean method and the corresponding degrees of equivalence obtained between each participant and the SCRV are presented. For total harmonic distortion and total distortion + noise measurements, SCRVs were not calculated and the values reported by participants are compared with the calculated arithmetic mean and weighted mean values. Overall, the supplementary comparison SIM.AUV.A-S2 was considered successful and fits its purpose.

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCAUV, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
The role of humidity and UV-C emission in the inactivation of B. subtilis spores during atmospheric-pressure dielectric barrier discharge treatment
Authors: Kogelheide Friederike , Voigt Farina , Hillebrand Bastian , Moeller Ralf , Fuchs Felix , Gibson Andrew R. , Awakowicz Peter , Stapelmann Katharina , Fiebrandt Marcel
Published: May 2020

Experiments are performed to assess the inactivation of Bacillus subtilis spores using a non-thermal atmospheric-pressure dielectric barrier discharge. The plasma source used in this study is mounted inside a vacuum vessel and operated in controlled gas mixtures. In this context, spore inactivation is measured under varying nitrogen/oxygen and humidity content and compared to spore inactivation using ambient air. Operating the dielectric barrier discharge in a sealed vessel offers the ability to distinguish between possible spore inactivation mechanisms since different process gas mixtures lead to the formation of distinct reactive species. The UV irradiance and the ozone density within the plasma volume are determined applying spectroscopic diagnostics with neither found to fully correlate with spore inactivation. It is found that spore inactivation is most strongly correlated with the humidity content in the feed gas, implying that reactive species formed, either directly or indirectly, from water molecules are strong mediators of spore inactivation.
High-pressure characterization of multifunctional CrVO4
Authors: Botella P , López-Moreno S , Errandonea D , Manjón F J , Sans J A , Vie D , Vomiero A
Published: May 2020

The structural stability and physical properties of CrVO4 under compression were studied by x-ray diffraction, Raman spectroscopy, optical absorption, resistivity measurements, and ab initio calculations up to 10 GPa. High-pressure x-ray diffraction and Raman measurements show that CrVO4 undergoes a phase transition from the ambient pressure orthorhombic CrVO4-type structure (Cmcm space group, phase III) to the high-pressure monoclinic CrVO4-V phase, which is proposed to be isomorphic to the wolframite structure. Such a phase transition (CrVO4-type → wolframite), driven by pressure, also was previously observed in indium vanadate. The crystal structure of both phases and the pressure dependence in unit-cell parameters, Raman-active modes, resistivity, and electronic band gap, are reported. Vanadium atoms are sixth-fold coordinated in the wolframite phase, which is related to the collapse in the volume at the phase transition. Besides, we also observed drastic changes in the phonon spectrum, a drop of the band-gap, and a sharp decrease of resistivity. All the observed phenomena are explained with the help of first-principles calculations.
Graphene-enabled reconfigurable terahertz wavefront modulator based on complete Fermi level modulated phase
Authors: Shang Xiongjun , Xu Liang , Yang Hui , He Hairong , He Qian , Huang Yu , Wang Lingling
Published: May 2020

Although great achievements have been obtained in metasurfaces so far, the functionalities of these devices are almost static. The dynamically adjustable devices are far less explored. Here we theoretically and numerically demonstrate a veritable reconfigurable terahertz wavefront modulator (TWM). The designed TWM can dynamically shape the wavefront at will via imposing different Fermi levels on the constituent graphene ribbons. By adopting the Dirac brackets and Matrix analyze method, the correlation between the phase shift and Fermi level is theoretically established, which offers a general scheme for designing dynamically switchable devices. As a proof of concept, three different sets of pre-calculated Fermi levels are imposed on the graphene ribbons. The TWM can be dynamically switched among back reflector, varifocal metalens and Airy beam generator, which has never been demonstrated before as far as we know. The proposed reconfigurable TWM owns the capability of dynamically steering terahertz wavefront, indicating great significance for the development of THz reconfigurable devices.
Characterizing disproportionality in facility-level toxic releases in US manufacturing, 1998–2012
Authors: Collins M , Pulver S , Hill D , Manski B
Published: May 2020

The relationship between economic activity and environmental pollution is a topic of extensive research. Although a proportional relationship between the two is often the default assumption, emerging scholarship suggests that polluting releases are disproportionally distributed across units of production. This paper examines if proportionality or disproportionality best characterizes the production of toxic pollution in US manufacturing from 1998 to 2012. Examining US Environmental Protection Agency Toxics Release Inventory data from over 25 000 facilities in 322 industries, we find consistently high levels of disproportionality across facility-level toxic releases within industries, even when controlling for facility size. Moreover, high levels of within industry disproportionality are remarkably stable over the fifteen-year study period. In other words, year by year a small handful of egregiously polluting facilities account for the vast majority of toxic releases within a given industry. Our findings suggest that disproportionality should be understood as the default pattern of pollution generation rather than an exceptional case and that policymakers should seek to reduce pollution via carefully considered targeting strategies rather than broad-stroke decision making.
Feedback regulation of BMP signaling byCaenorhabditis eleganscuticle collagens
Authors: Madaan Uday , Faure Lionel , Chowdhury Albar , Ahmed Shahrear , Ciccarelli Emma J. , Gumienny Tina L. , Savage-Dunn Cathy
Published: May 2020

Transforming growth factor beta (TGF-β) and related signals can be regulated by the extracellular matrix (ECM). We identify a novel contact-independent regulation of DBL-1 TGF-β/BMP–related signaling by collagens in Caenorhabditis elegans. These collagens are transcriptional targets of the pathway, indicating reciprocal interactions between DBL-1 signaling and the ECM.
Dynamin 2 interacts with α-actinin 4 to drive tumor cell invasion
Authors: Burton Kevin M. , Cao Hong , Chen Jing , Qiang Li , Krueger Eugene W. , Johnson Katherine M. , Bamlet William R. , Zhang Lizhi , McNiven Mark A. , Razidlo Gina L.
Published: May 2020

Dyn2 and α-actinin 4 interact directly to regulate invasive cell migration and the stabilization of invadopodia. Intriguingly, this is specific for α-actinin 4, and not the highly related protein α-actinin 1. These findings elucidate a novel mechanism of regulating cell migration, with important implications for invasive tumor cells.
Dynactin p150 promotes processive motility of DDB complexes by minimizing diffusional behavior of dynein
Authors: Feng Qingzhou , Gicking Allison M. , Hancock William O.
Published: May 2020

Dynein–dynactin–BicD2 (DDB) is highly processive, but also shows transient pausing and diffusion, which we analyzed using iSCAT microscopy. Blocking dynactin p150 results in more diffusion of isolated DDB and a plus-end shift of kinesin-1–DDB complexes. Thus, we conclude that p150 is an allosteric activator of dynein in the DDB complex.
Contribution of increasing plasma membrane to the energetic cost of early zebrafish embryogenesis
Authors: Rodenfels Jonathan , Sartori Pablo , Golfier Stefan , Nagendra Kartikeya , Neugebauer Karla M. , Howard Jonathon
Published: May 2020

The energetic costs of development were measured during early embryogenesis in zebrafish using calorimetry. The heat dissipated by the embryo increased with time. The heat dissipation scaled with the increasing surface area of the plasma membrane, suggesting that the energetic costs are associated with maintaining and/or producing plasma membrane.
Cytoplasmic Expression of CD3ε Heterodimers by Flow Cytometry Rapidly Distinguishes Between Mature T-Cell and Natural Killer–Cell Neoplasms
Authors: Shi Min , Nguyen Phuong , Timm Michael M , Otteson Gregory E , Horna Pedro , Olteanu Horatiu , Jevremovic Dragan
Published: May 2020

Objectives

Distinguishing between T-cell and natural killer (NK)–cell neoplasms could be difficult given their overlapping immunophenotype. In this study, we investigated whether a flow cytometry assay with cytoplasmic staining for CD3 could be used for this purpose.

Methods

Flow cytometry immunophenotyping was performed on 19 surface CD3 (sCD3)–negative mature T-cell neoplasms, 10 sCD3-positive mature T-cell neoplasms, 13 mature NK-cell neoplasms, and 19 normal controls. In addition to routine antibody panels (CD2, sCD3, CD4, CD5, CD7, CD8, CD16, CD45, CD56, CD57, CD94, CD158a, CD158b, CD158e, NKG2A TCRγ/δ), cytoplasmic staining for a monoclonal CD3 antibody (clone SK7/Leu-4) was assessed in all cases. A molecular study for T-cell receptor (TCR) gene rearrangement and an immunohistochemical study for TCRβ were performed.

Results

Our data showed all T-cell neoplasms were uniformly positive for cytoplasmic CD3 (cCD3) regardless of sCD3 expression, whereas 85% of NK-cell neoplasms completely lacked cCD3 expression. The 2 cases with classic NK-cell immunophenotype but partial cCD3 expression showed no molecular genetic features of T-cell lineage by TCR gene rearrangement studies.

Conclusions

Uniform cCD3 positivity and homogeneous cCD3 negativity highly suggest T-cell and NK lineage, respectively. When partial cCD3 expression is encountered, additional confirmatory studies should be pursued for the most accurate lineage assignment.
Alternative motivation and lies
Authors: Sneddon Andrew
Published: May 2020

An array of new cases of lies is presented in support of the idea that lying does not require an intention to be deceptive. The crucial feature of these cases is that the agents who lie have some sort of motivation to lie alternative to an intention to be deceptive. Such alternative motivation comes in multiple varieties, such that we should think that the possibility of lying without an intention to be deceptive is common.
News in Astronomy & Geophysics – June 2020
Authors: Bowler Sue
Published: May 2020

A digest of some of the big stories from the past two months
Heather Couper (1949–2020)
Authors: Henbest Nigel
Published: May 2020

Nigel Henbest recalls a meteoric career in science communication.
Meeting expectations
Authors: Bowler Sue
Published: May 2020

Sue Bowler chats with the organizers of the 13 March RAS Specialist Discussion Meeting “The near-Sun solar wind at solar minimum” about how they made it work for attendees in person and online – and the challenges and opportunities for our communities in the coming months.
Deep learning for the Sun
Authors: Armstrong John A , Osborne Christopher M J , Fletcher Lyndsay
Published: May 2020

John A Armstrong, Christopher M J Osborne and Lyndsay Fletcher examine how neural networks can be used to explore the nature and location of solar activity.
Predictive and interpretable models via the stacked elastic net
Authors: Rauschenberger Armin , Glaab Enrico , van de Wiel Mark A
Published: May 2020

Motivation

Machine learning in the biomedical sciences should ideally provide predictive and interpretable models. When predicting outcomes from clinical or molecular features, applied researchers often want to know which features have effects, whether these effects are positive or negative and how strong these effects are. Regression analysis includes this information in the coefficients but typically renders less predictive models than more advanced machine learning techniques.

Results

Here, we propose an interpretable meta-learning approach for high-dimensional regression. The elastic net provides a compromise between estimating weak effects for many features and strong effects for some features. It has a mixing parameter to weight between ridge and lasso regularization. Instead of selecting one weighting by tuning, we combine multiple weightings by stacking. We do this in a way that increases predictivity without sacrificing interpretability.

Availability and implementation

The R package starnet is available on GitHub (https://github.com/rauschenberger/starnet) and CRAN (https://CRAN.R-project.org/package=starnet).
Patients’ Experiences With Staphylococcus aureus and Gram-negative Bacterial Bloodstream Infections: A Qualitative Descriptive Study and Concept Elicitation Phase To Inform Measurement of Patient-reported Quality of Life
Authors: King Heather A , Doernberg Sarah B , Miller Julie , Grover Kiran , Oakes Megan , Ruffin Felicia , Gonzales Sarah , Rader Abigail , Neuss Michael J , Bosworth Hayden B , Sund Zoë , Drennan Caitlin , Hill-Rorie Jonathan M , Shah Pratik , Winn Laura , Fowler Vance G , Holland Thomas L
Published: May 2020

Background

Although Staphylococcus aureus and gram-negative bacterial bloodstream infections (SAB/GNB) cause substantial morbidity, little is known regarding patient perceptions’ of their impact on quality of life (QOL). Guidance for assessing QOL and disease-specific measures are lacking. We conducted a descriptive qualitative study to gain an in-depth understanding of patients’ experiences with SAB/GNB and concept elicitation phase to inform a patient-reported QOL outcome measure.

Methods

We conducted prospective one-time, in-depth, semi-structured, individual, qualitative telephone interviews 6– 8 weeks following bloodstream infection with either SAB or GNB. Patients were enrolled in an institutional registry (tertiary academic medical center) for SAB or GNB. Interviews were audio-recorded, transcribed, and coded. Directed content analysis identified a priori and emergent themes. Theme matrix techniques were used to facilitate analysis and presentation.

Results

Interviews were completed with 30 patients with SAB and 31 patients with GNB. Most patients were at or near the end of intravenous antibiotic treatment when interviewed. We identified 3 primary high-level concepts: impact on QOL domains, time as a critical index, and sources of variability across patients. Across both types of bloodstream infection, the QOL domains most impacted were physical and functional, which was particularly evident among patients with SAB.

Conclusions

SAB/GNB impact QOL among survivors. In particular, SAB had major impacts on multiple QOL domains. A combination of existing, generic measures that are purposefully selected and disease-specific items, if necessary, could best capture these impacts. Engaging patients as stakeholders and obtaining their feedback is crucial to conducting patient-centered clinical trials and providing patient-centered care.
Concordance of Drug-resistance Profiles Between Persons With Drug-resistant Tuberculosis and Their Household Contacts: A Systematic Review and Meta-analysis
Authors: Chiang Silvia S , Brooks Meredith B , Jenkins Helen E , Rubenstein Dana , Seddon James A , van de Water Brittney J , Lindeborg Michael M , Becerra Mercedes C , Yuen Courtney M
Published: May 2020

Background

Household contacts of patients with drug-resistant tuberculosis (TB) are at high risk for being infected with Mycobacterium tuberculosis and for developing TB disease. To guide regimen composition for the empirical treatment of TB infection and disease in these household contacts, we estimated drug-resistance profile concordance between index patients with drug-resistant TB and their household contacts.

Methods

We performed a systematic review and meta-analysis of studies published through 24 July 2018 that reported resistance profiles of drug-resistant TB index cases and secondary cases within their households. Using a random-effects meta-analysis, we estimated resistance profile concordance, defined as the percentage of secondary cases whose M. tuberculosis strains were resistant to the same drugs as strains from their index cases. We also estimated isoniazid/rifampin concordance, defined as whether index and secondary cases had identical susceptibilities for isoniazid and rifampin only.

Results

We identified 33 eligible studies that evaluated resistance profile concordance between 484 secondary cases and their household index cases. Pooled resistance profile concordance was 54.3% (95% confidence interval [CI], 40.7–67.6%; I2 = 85%). Pooled isoniazid/rifampin concordance was 82.6% (95% CI, 72.3–90.9%; I2 = 73%). Concordance estimates were similar in a subanalysis of 16 studies from high-TB-burden countries. There were insufficient data to perform a subanalysis among pediatric secondary cases.

Conclusions

Household contacts of patients with drug-resistant TB should receive treatment for TB infection and disease that assumes that they, too, are infected with a drug-resistant M. tuberculosis strain. Whenever possible, drug susceptibility testing should be performed for secondary cases to optimize regimen composition.
Loss of Snord116 alters cortical neuronal activity in mice: a preclinical investigation of Prader–Willi syndrome
Authors: Pace Marta , Colombi Ilaria , Falappa Matteo , Freschi Andrea , Bandarabadi Mojtaba , Armirotti Andrea , Encarnación Blanco María , Adamantidis Antoine R , Amici Roberto , Cerri Matteo , Chiappalone Michela , Tucci Valter
Published: May 2020

Prader–Willi syndrome (PWS) is a neurodevelopmental disorder that is characterized by metabolic alteration and sleep abnormalities mostly related to rapid eye movement (REM) sleep disturbances. The disease is caused by genomic imprinting defects that are inherited through the paternal line. Among the genes located in the PWS region on chromosome 15 (15q11-q13), small nucleolar RNA 116 (Snord116) has been previously associated with intrusions of REM sleep into wakefulness in humans and mice. Here, we further explore sleep regulation of PWS by reporting a study with PWScrm+/p− mouse line, which carries a paternal deletion of Snord116. We focused our study on both macrostructural electrophysiological components of sleep, distributed among REMs and nonrapid eye movements. Of note, here, we study a novel electroencephalography (EEG) graphoelements of sleep for mouse studies, the well-known spindles. EEG biomarkers are often linked to the functional properties of cortical neurons and can be instrumental in translational studies. Thus, to better understand specific properties, we isolated and characterized the intrinsic activity of cortical neurons using in vitro microelectrode array. Our results confirm that the loss of Snord116 gene in mice influences specific properties of REM sleep, such as theta rhythms and, for the first time, the organization of REM episodes throughout sleep–wake cycles. Moreover, the analysis of sleep spindles present novel specific phenotype in PWS mice, indicating that a new catalog of sleep biomarkers can be informative in preclinical studies of PWS.
Decrease in serum alkaline phosphatase and prognostic relevance in adult cardiopulmonary bypass
Authors: Schaefer Anne-Kristin , Hutschala Doris , Andreas Martin , Bernardi Martin H , Brands Ruud , Shabanian Shiva , Laufer Günther , Wiedemann Dominik
Published: May 2020

OBJECTIVES

Cardiopulmonary bypass (CPB) induces inflammatory responses, which may lead to the loss of alkaline phosphatase (AP) that is consumed in the process of dephosphorylating detrimental extracellular nucleotides in this proinflammatory state. It has been reported that low postoperative AP levels correlate with increased postoperative support requirement and organ dysfunction after paediatric cardiac surgery. However, little is known about the perioperative development and clinical relevance of AP depletion in adults undergoing CPB.

METHODS

A total of 183 patients with a preoperative left ventricular ejection fraction ≤50% undergoing mitral valve surgery ± concomitant related procedures at the Department of Cardiac Surgery, Medical University of Vienna, between 2013 and 2016 were included in this retrospective analysis. Serum AP measurements at baseline and on postoperative days 1–15 were collected. Absolute and relative drop of AP on postoperative day 1 from baseline was correlated with perioperative and early postoperative parameters. Receiver operating characteristics were used to define suitable predictors and cut-offs for postoperative outcome variables.

RESULTS

Receiver operating characteristics showed a reduction of >50% of baseline AP to predict in-hospital mortality [area under the curve (AUC) 0.807], prolonged intensive care unit stay (>72 h, AUC 0.707), prolonged mechanical ventilation (>24 h, AUC 0.712) and surgery-related dialysis requirement (AUC 0.736). Patients with a perioperative reduction in circulating AP to levels below 50% of baseline had a significantly decreased survival. Patients with high perioperative AP loss had higher preoperative AP levels (P < 0.001), longer CPB duration (P < 0.001) and higher incidence of extracorporeal membrane oxygenation support (P < 0.001).

CONCLUSIONS

Increased perioperative AP loss is associated with adverse early outcome. Prospective trials are needed to determine whether this effect can be counteracted by perioperative AP supplementation.
Relevance of Electrical Light on Circadian, Neuroendocrine, and Neurobehavioral Regulation in Laboratory Animal Facilities
Authors: Hanifin John P , Dauchy Robert T , Blask David E , Hill Steven M , Brainard George C
Published: May 2020

Light is a key extrinsic factor to be considered in operations and design of animal room facilities. Over the past four decades, many studies on typical laboratory animal populations have demonstrated impacts on neuroendocrine, neurobehavioral, and circadian physiology. These effects are regulated independently from the defined physiology for the visual system. The range of physiological responses that oscillate with the 24 hour rhythm of the day include sleep and wakefulness, body temperature, hormonal secretion, and a wide range of other physiological parameters. Melatonin has been the chief neuroendocrine hormone studied, but acute light-induced effects on corticosterone as well as other hormones have also been observed. Within the last two decades, a new photosensory system in the mammalian eye has been discovered. A small set of retinal ganglion cells, previously thought to function as a visual output neuron, have been shown to be directly photosensitive and act differently from the classic photoreceptors of the visual system. Understanding the effects of light on mammalian physiology and behavior must take into account how the classical visual photoreceptors and the newly discovered ipRGC photoreceptor systems interact. Scientists and facility managers need to appreciate lighting impacts on circadian, neuroendocrine, and neurobehavioral regulation in order to improve lighting of laboratory facilities to foster optimum health and well-being of animals.
Oxycodone Concentrations and Metabolic Ratios in Femoral Blood from Fatal Intoxications and Other Causes of Death using LC–MS-MS
Authors: Jakobsson Gerd , Gréen Henrik , Kronstrand Robert
Published: May 2020

Oxycodone (OC) is an opioid with strong analgesic effects widely used to treat acute and chronic pain. Interpretation of OC concentrations in postmortem cases is complicated due to tolerance and overlapping concentrations for fatal and non-fatal levels. In this study, our aim was to develop and validate a method for OC and its three metabolites: noroxycodone (NOC), oxymorphone (OM) and noroxymorphone (NOM) in postmortem femoral blood. Our goal was to define reference concentrations for intoxications and non-intoxications and investigate metabolic ratios in different causes of death. A rapid LC–MS-MS method using protein-precipitated postmortem blood was developed. Lower limit of quantitation was 0.005 μg/g blood for all analytes; upper limit of quantitation was 1.0 μg/g for OC and NOC and 0.25 μg/g for OM and NOM. The method displayed high precision (3.3–7.7%) and low bias (−0.3 to 12%). In total, 192 cases were analyzed and concentrations ranged from 0.005 to 13 μg/g for OC, 0.005 to 2.0 μg/g for NOC, 0.005 to 0.24 μg/g for OM, and 0.005 to 0.075 μg/g for NOM. We found a significant difference in OC concentration between the cases where OC contributed and those where it did not. In spite of that, we do not recommend the use of a specific blood concentration to distinguish fatal intoxications. Instead, the percentiles from our data set suggest that concentrations >0.2 μg/g are likely to have contributed to toxicity, but that concentrations as high as 0.3 might be tolerated without toxic effects. In addition, we also found that a low NOC/OC ratio could point toward an acute fatal intoxication. In conclusion, the OC concentration alone may not be sufficient to diagnose a fatal intoxication.
The Effects of Numerical Divisibility on Loneliness Perceptions and Consumer Preferences
Authors: Yan Dengfeng , Sengupta Jaideep
Published: May 2020

This research seeks to examine, first, whether and why consumers perceive divisible versus indivisible numbers differently and, second, how such divergent perceptions influence consumer preferences for marketer-created entities associated with divisible versus indivisible numbers. Integrating insights from two different literatures—numerical cognition and loneliness—we propose and find that numbers perceived to be divisible (vs. indivisible) are viewed as having more “connections” and are therefore deemed to be less lonely. Building on these findings and the literature on compensatory consumption, we then propose and demonstrate that a temporary feeling of loneliness increases participants’ relative preference for various targets—products, attributes, and prices—associated with divisible (vs. indivisible) numbers, which are perceived to be relatively more connected and less lonely. It merits mention that our findings are triangulated across a wide variety of numbers, different product categories, and multiple operationalizations of loneliness.
The women behind Times New Roman
Authors: Savoie Alice
Published: May 2020

The narrative behind the creation of Times New Roman, one of the most widely used typefaces in the western world, is well established and revolves around famous male figures of British typographic history. This article recognises the role played by the Monotype Type Drawing Office (TDO), and of its draughtswomen in particular, in the making of the typeface. While female figures are largely absent from type histories, this contribution emphasises the key role played by the women who worked on adapting Stanley Morison’s original idea for Times New Roman into a fully working, extensive type family. Based on original archival material, it discusses the background of these women, their working conditions, and the nature of their contribution to type-making. In a wider perspective, this article advocates a more inclusive and collaborative view of design history and of its narratives.
Protective or connective professionalism? How connected professionals can (still) act as autonomous and authoritative experts
Authors: Noordegraaf Mirko
Published: May 2020

Traditionally, professionals such as medical doctors, lawyers, and academics are protected. They work within well-defined jurisdictions, belong to specialized segments, have been granted autonomy, and have discretionary spaces. In this way, they can be socialized, trained, and supervised, case-related considerations and decisions can be substantive (instead of commercial), and decisions can be taken independently. Ideally, these decisions are authoritative and accepted, both by clients as well as society (stakeholders) who trust professional services. This ideal-typical but also ‘ideal’ imagery always had its flaws; nowadays, shortcomings are increasingly clear. ‘Protective professionalism’ is becoming outdated. Due to heterogeneity and fragmentation within professional fields, the interweaving of professional fields, and dependencies of professional actions on outside worlds, professionals can no longer isolate themselves from others and outsiders. At first sight, this leads to a ‘decline’, ‘withering away’, or ‘hollowing out’ of professionalism. Or it leads to attempts to ‘reinstall’, ‘reinvent’, or ‘return to’ professional values and spaces. In this article, we avoid such ‘all or nothing’ perspectives on changing professionalism and explore the ‘reconfiguration’ of professionalism. Professional identities and actions can be adapted and might become ‘hybrid’, ‘organized’, and ‘connected’. Professional and organizational logics might be interrelated; professionals might see organizational (or organizing) duties as belonging to their work; and professional fields might open up to outside worlds. We particularly explore connective professionalism, arguing that we need more fundamental reflections and redefinitions of what professionalism means and what professionals are. We focus on the question of how professional action can be related to others and outsiders and remain ‘knowledgeable’, ‘autonomous’, and ‘authoritative’ at the same time. This can no longer be a matter of expertise, autonomy, and authority as fixed and closed entities. These crucial dimensions of professional action become relational and processual. They have to be enacted on a continuous basis, backed by mechanisms that make professionalism knowledgeable, independent, and authoritative in the eyes of others.
A low-mass stellar companion to the young variable star RZ Psc
Authors: Kennedy Grant M , Ginski Christian , Kenworthy Matthew A , Benisty Myriam , Henning Thomas , van Holstein Rob G , Kral Quentin , Ménard François , Milli Julien , Quiroga-Nuñez Luis Henry , Rab Christian , Stolker Tomas , Sturm Ardjan
Published: May 2020

RZ Psc is a young Sun-like star with a bright and warm infrared excess that is occasionally dimmed significantly by circumstellar dust structures. Optical depth arguments suggest that the dimming events do not probe a typical sightline through the circumstellar dust, and are instead caused by structures that appear above an optically thick mid-plane. This system may therefore be similar to systems where an outer disc is shadowed by material closer to the star. Here, we report the discovery that RZ Psc hosts a $0.12\, \mathrm{ M}_\odot$ companion at a projected separation of 23 au. We conclude that the disc must orbit the primary star. While we do not detect orbital motion, comparison of the angle of linear polarization of the primary with the companion’s on-sky position angle provides circumstantial evidence that the companion and disc may not share the same orbital plane. Whether the companion severely disrupts the disc, truncates it, or has little effect at all will require further observations of both the companion and disc.
Chaperone-Mediated Autophagy in the Light of Evolution: Insight from Fish
Authors: Lescat Laury , Véron Vincent , Mourot Brigitte , Péron Sandrine , Chenais Nathalie , Dias Karine , Riera-Heredia Natàlia , Beaumatin Florian , Pinel Karine , Priault Muriel , Panserat Stéphane , Salin Bénédicte , Guiguen Yann , Bobe Julien , Herpin Amaury , Seiliez Iban
Published: May 2020

Chaperone-mediated autophagy (CMA) is a major pathway of lysosomal proteolysis recognized as a key player of the control of numerous cellular functions, and whose defects have been associated with several human pathologies. To date, this cellular function is presumed to be restricted to mammals and birds, due to the absence of an identifiable lysosome-associated membrane protein 2A (LAMP2A), a limiting and essential protein for CMA, in nontetrapod species. However, the recent identification of expressed sequences displaying high homology with mammalian LAMP2A in several fish species challenges that view and suggests that CMA likely appeared earlier during evolution than initially thought. In the present study, we provide a comprehensive picture of the evolutionary history of the LAMP2 gene in vertebrates and demonstrate that LAMP2 indeed appeared at the root of the vertebrate lineage. Using a fibroblast cell line from medaka fish (Oryzias latipes), we further show that the splice variant lamp2a controls, upon long-term starvation, the lysosomal accumulation of a fluorescent reporter commonly used to track CMA in mammalian cells. Finally, to address the physiological role of Lamp2a in fish, we generated knockout medaka for that specific splice variant, and found that these deficient fish exhibit severe alterations in carbohydrate and fat metabolisms, in consistency with existing data in mice deficient for CMA in liver. Altogether, our data provide the first evidence for a CMA-like pathway in fish and bring new perspectives on the use of complementary genetic models, such as zebrafish or medaka, for studying CMA in an evolutionary perspective.
CLUE: a bioinformatic and wet-lab pipeline for multiplexed cloning of custom sgRNA libraries
Authors: Becker Martin , Noll-Puchta Heidi , Amend Diana , Nolte Florian , Fuchs Christiane , Jeremias Irmela , Braun Christian J
Published: May 2020

The systematic perturbation of genomes using CRISPR/Cas9 deciphers gene function at an unprecedented rate, depth and ease. Commercially available sgRNA libraries typically contain tens of thousands of pre-defined constructs, resulting in a complexity challenging to handle. In contrast, custom sgRNA libraries comprise gene sets of self-defined content and size, facilitating experiments under complex conditions such as in vivo systems. To streamline and upscale cloning of custom libraries, we present CLUE, a bioinformatic and wet-lab pipeline for the multiplexed generation of pooled sgRNA libraries. CLUE starts from lists of genes or pasted sequences provided by the user and designs a single synthetic oligonucleotide pool containing various libraries. At the core of the approach, a barcoding strategy for unique primer binding sites allows amplifying different user-defined libraries from one single oligonucleotide pool. We prove the approach to be straightforward, versatile and specific, yielding uniform sgRNA distributions in all resulting libraries, virtually devoid of cross-contaminations. For in silico library multiplexing and design, we established an easy-to-use online platform at www.crispr-clue.de. All in all, CLUE represents a resource-saving approach to produce numerous high quality custom sgRNA libraries in parallel, which will foster their broad use across molecular biosciences.
Phylogenetic patterns suggest frequent multiple origins of secondary metabolites across the seed-plant ‘tree of life’
Authors: Zhang Yongzeng , Deng Tao , Sun Lu , Landis Jacob B , Moore Michael J , Wang Hengchang , Wang Yuehua , Hao Xiaojiang , Chen Jijun , Li Shenghong , Xu Maonian , Puno Pema-Tenzin , Raven Peter H , Sun Hang
Published: May 2020

To evaluate the phylogenetic patterns of the distribution and evolution of plant secondary metabolites (PSMs), we selected 8 classes of PSMs and mapped them onto an updated phylogenetic tree including 437 families of seed plants. A significant phylogenetic signal was detected in 17 of the 18 tested seed-plant clades for at least 1 of the 8 PSM classes using the D statistic. The phylogenetic signal, nevertheless, indicated weak clustering of PSMs compared to a random distribution across all seed plants. The observed signal suggests strong diversifying selection during seed-plant evolution and/or relatively weak evolutionary constraints on the evolution of PSMs. In the survey of the current phylogenetic distributions of PSMs, we found that multiple origins of PSM biosynthesis due to external selective forces for diverse genetic pathways may have played important roles. In contrast, a single origin of PSMs seems rather uncommon. The distribution patterns for PSMs observed in this study may also be useful in the search for natural compounds for medicinal purposes.
A Critical Analysis of the Kampala Convention from a Children’s Rights Perspective
Authors: Fawole Charissa E
Published: May 2020

A notable proportion of the persons living in situations of internal displacement in Africa are children. Despite the near-universal ratification of the Convention on the Rights of the Child and the wide ratification of the African Charter on the Rights and Welfare of the Child among States in Africa, it is not clear the extent to which the ratification of these treaties has influenced the region’s legal framework for the protection and assistance of internally displaced children. This contribution addresses this issue through its analysis of the African Union Convention for the Protection and Assistance of Internally Displaced Persons in Africa from a children’s rights perspective. While the Convention does incorporate some principles of a children’s rights perspective, the analysis reveals that there are some inadequacies regarding the Convention’s overall incorporation of a children’s rights perspective. Based on the analysis, this contribution provides recommendations to use a children’s rights perspective to implement the Convention.