bluuebunny/crossref_metadata_2025 huggingface dataset:
Could application of leader-member exchange theory have saved a residency mentorship program?
Authors: Bunin Jessica L. , Meyer Holly S. , Durning Steven J.
Published: May 2020

Mentorship may offer protégés numerous benefits including improved self-esteem, increased interest in research, and/or enhanced productivity. Without proper planning, reflection, and evaluation, however, mentorship programs may result in undesirable consequences. In this paper we describe a mentorship program designed to improve psychosocial support and professional development for residents, that while initially successful, was terminated due to perceptions of inequity that led to strife among residents and ultimately created a toxic learning climate. Leader-member exchange theory provides a lens through which to view our program’s failure and to offer some potential solutions to mitigate such challenges for other programs. Leader-member exchange theory focuses on the importance of relationships, communication, and awareness of biases to optimize interactions between dyads such as a mentor and a protégé. We highlight opportunities during the stranger, acquaintance, and mature partnership phases that could have helped to save a residency mentorship program.
“The storm has arrived”: the impact of SARS-CoV-2 on medical students
Authors: Klasen Jennifer M. , Vithyapathy Akschaya , Zante Bjoern , Burm Sarah
Published: May 2020

In a few weeks, the global community has witnessed, and for some of us experienced first-hand, the human costs of the COVID-19 pandemic. There is incredible variability in how countries are choosing to thwart the disease’s outbreak, sparking intense discussions around what it means to teach and learn in the era of COVID-19, and more specifically, the role medical students play in the midst of the pandemic. A multi-national and multi-institutional group made up of a dedicated medical student from Austria, passionate clinicians and educators from Switzerland, and a PhD scientist involved in Medical Education from Canada, have assembled to summarize the ingenious ways medical students around the world are contributing to emergency efforts. They argue that such efforts change COVID-19 from a “disruption” to medical students learning to something more tangible, more important, allowing students to become stakeholders in the expansion and delivery of healthcare.
Zur naturwissenschaftlich-technischen Friedens- und Konfliktforschung: Aktuelle Herausforderungen und Bewertung der Empfehlungen des Wissenschaftsrats
Authors: Reuter Christian , Altmann Jürgen , Göttsche Malte , Himmel Mirko
Published: May 2020

Die besorgniserregende Aufkündigung des INF-Vertrags, der wiederholte Einsatz von Chemiewaffen in Syrien, kontroverse Diskussionen über die Einführung autonomer Waffensysteme oder zunehmende Cyber-Bedrohungen prägen das aktuelle politische Weltgeschehen. Besonders in einer Zeit, in der nukleare, biologische und chemische Abrüstung- und Rüstungskontrollmaßnahmen vor großen Herausforderungen stehen und gleichzeitig neue Technologien veränderte Anforderungen an diese Kontrollmechanismen mit sich bringen, gewinnt die naturwissenschaftlich-technische Friedensforschung enorm an Bedeutung. Sie beschäftigt sich auf der Grundlage von Erkenntnissen aus verschiedenen Naturwissenschaften und technischen Fachrichtungen (z. B. Physik, Chemie, Biologie, Informatik) mit der Rolle naturwissenschaftlicher und technischer Möglichkeiten im Kontext von Krieg und Frieden sowie Rüstung und Abrüstung. Sie unterstützt die politischen Prozesse der Kriegsprävention, der Abrüstung und der Vertrauensbildung mit Analysen der Eigenschaften und Folgen neuer Waffenarten und Technologien. Aus dieser Forschung werden Vorschläge für die Begrenzung neuer Waffenentwicklungen ebenso entwickelt wie technische Lösungen für eine verbesserte Rüstungskontrolle. Dieser Artikel benennt aktuelle Herausforderungen der naturwissenschaftlich-technischen Friedensforschung und geht dabei auch auf die aktuellen Empfehlungen des Wissenschaftsrats zur Weiterentwicklung der Friedens- und Konfliktforschung aus dem Jahr 2019 ein.
Examining child protection practice in New South Wales: Non-accidental injury and the principle of strict liability
Authors: Hansen Patricia , Ainsworth Frank
Published: May 2020

This article examines child protection practice when the Department of Communities and Justice in New South Wales takes the view that an injury to a child is non-accidental. The position taken in this paper is that once a child protection caseworker takes the position that an injury is non-accidental, then a strict liability or absolute liability approach is adopted. In effect, any of the child’s parents or caregivers are identified as persons who may have caused the injury or harm. What follows is the decision that a child must never be restored to the parents or caregivers, unless a person confesses to causing the harm and completes specific child protection counselling. Our concern is with the process of investigation, the reliance on one medical opinion in a context where the parents or caregivers are not in a financial position to obtain a second opinion, the failure to observe the rules of evidence when considering medical opinion, and the manner of substantiation of the non-accidental injury. In addition, we argue that there is a lack of knowledge about the factors that influence a paediatrician’s decision-making and that the guidelines for judicial decision-making derived from case law need to be examined further.
Raising strong, solid Koolunga: values and beliefs about early child development among Perth’s Aboriginal community
Authors: Scrine Clair , Farrant Brad , Michie Carol , Shepherd Carrington , Wright Michael
Published: May 2020

There is a paucity of published information about conceptions of Aboriginal child rearing and development among urban dwelling Nyoongar/Aboriginal people in Australia. We detail the unique findings from an Aboriginal early child development research project with a specific focus on the Nyoongar/Aboriginal community of Perth, Western Australia. This research significantly expands the understanding of a shared system of beliefs and values among Nyoongar people that differ in important ways from those of the broader Australian (Western) society. Consistent with the findings of research with other Aboriginal groups in Australia, and internationally, our work challenges assumptions underpinning a range of early childhood development policies and highlights the implications of cultural biases and misunderstandings among non-Aboriginal professionals in child and family services, education and other settings.
HALF-SPACE MACDONALD PROCESSES
Authors: BARRAQUAND GUILLAUME , BORODIN ALEXEI , CORWIN IVAN
Published: May 2020

Macdonald processes are measures on sequences of integer partitions built using the Cauchy summation identity for Macdonald symmetric functions. These measures are a useful tool to uncover the integrability of many probabilistic systems, including the Kardar–Parisi–Zhang (KPZ) equation and a number of other models in its universality class. In this paper, we develop the structural theory behind half-space variants of these models and the corresponding half-space Macdonald processes. These processes are built using a Littlewood summation identity instead of the Cauchy identity, and their analysis is considerably harder than their full-space counterparts.

We compute moments and Laplace transforms of observables for general half-space Macdonald measures. Introducing new dynamics preserving this class of measures, we relate them to various stochastic processes, in particular the log-gamma polymer in a half-quadrant (they are also related to the stochastic six-vertex model in a half-quadrant and the half-space ASEP). For the polymer model, we provide explicit integral formulas for the Laplace transform of the partition function. Nonrigorous saddle-point asymptotics yield convergence of the directed polymer free energy to either the Tracy–Widom (associated to the Gaussian orthogonal or symplectic ensemble) or the Gaussian distribution depending on the average size of weights on the boundary.
Caregiving burden and mental health problems among family caregivers of people with dementia in rural Uganda
Authors: Ainamani Herbert E. , Alele Paul E. , Rukundo Godfrey Z. , Maling Samuel , Wakida Edith K. , Obua Celestino , Tsai Alexander C.
Published: May 2020

Background

Alzheimer's disease and related dementias are associated with increasing health burden in low- and middle-income countries. Less well-recognized is the potential health burden experienced by other affected individuals, such as family caregivers. In this study, we sought to profile the burden of care and its association with symptoms of depression and anxiety among informal caregivers of people living with dementia in rural southwestern Uganda.

Method

We conducted a cross-sectional study of 232 family caregivers of people with dementia. The key measured variables of interest were caregiving burden (Zarit Burden Index) and symptoms of depression and anxiety (Depression Anxiety Stress Scales). We fitted multivariable regression models specifying depression and anxiety symptoms as the primary outcomes of interest and caregiving burden as the primary explanatory variable of interest.

Results

Family caregivers of people with dementia experience significant caregiving burden, with each item on the Zarit Burden Index endorsed by more than 70% of study participants. Nearly half [108 (47%)] of caregivers had Zarit Burden Interview scores >60, suggestive of severe caregiving burden. In multivariable regression models, we estimated a statistically significant positive association between caregiving burden and symptoms of both depression [b= 0.42; 95% confidence interval (CI) 0.34–0.49] and anxiety (b= 0.37; 95% CI 0.30–0.45).

Conclusion

Family caregivers of people with dementia in rural Uganda experience a high caregiving burden, which is associated with symptoms of depression and anxiety. Interventions aimed at reducing caregiving burden may have important collateral mental health benefits.
The 2019 European Parliament election in the UK
Authors: Martill Benjamin
Published: May 2020

This article examines the 2019 European Parliament election in the UK. The main beneficiaries were the newly formed Brexit Party and the Liberal Democrats, both of which ran on clear Brexit platforms, while the Conservatives and Labour struggled to attract support. But the Brexit focus of the campaign – and the victory of parties with clear positions on these issues – belied the extent to which the election conformed to the expectations of second-order contest theory, with low turnout, declining support for the governing (Conservative) party, a surge in support for new and small parties, and scant discussion of European Union-level issues. While the vote shows realignment in the UK continues and can tell us much about the shifting politics of Brexit, we should be cautious inferring much from the victory of the Brexit Party and the Liberal Democrats given the second-order nature of the contest.
Carving the body at its joints: Does the way we speak about the body shape the way we think about it?
Authors: DEVYLDER SIMON , BRACKS CHRISTOPH , SHIMOTORI MISUZU , SIAHAAN POPPY
Published: May 2020

Looking at the way different linguistic communities speak about a universally shared domain of experience raises questions that are central to the language sciences. How can we compare meaning across languages? What is the interaction between language, thought, and perception? Does linguistic diversity entail linguistic relativism? The literature on the naming systems of the body across languages have addressed these questions with little consensus. In the present study, we contribute to this debate with a comparison of body part terms in French, Indonesian, and Japanese. Using an updated version of the body coloring task, we observed both diversity and cross-linguistically shared patterns. Importantly, we also observed that speakers of languages which violate the wrist/ankle joint boundary rule do not collapse the distinction in thought. This key finding goes against the conflation of language and thought and leads us to conclude that linguistic diversity does not entail linguistic relativism. Methodologically, we advocate for the use of a culturally neutral etic space as a necessary tool in semantic typology. Theoretically, we propose that language is a multilevel phenomenon, which results from the interaction of non-linguistic and cross-culturally shared embodied motivations, context-specific situated language use, and culturally specific sedimented linguistic conventions.
Roman Wales: Aerial Discoveries and New Observations from the Drought of 2018
Authors: Driver Toby G. , Burnham Barry C. , Davies Jeffrey L.
Published: May 2020

This paper provides description and context for some of the discoveries made by the Royal Commission on the Ancient and Historical Monuments of Wales during aerial reconnaissance in the drought conditions of the summer of 2018. New discoveries include two marching camps, three auxiliary forts and a remarkable series of stone buildings outside the fort at Pen y Gaer. The photographs also clarify the plan of several known villas as well as identifying some potential villa sites and enclosure systems of probable Romano-British date in south-eastern, south-western and north-western Wales. The recognition of a new road alignment south of Carmarthen is suggestive of another coastal fort at or near Kidwelly.
Using the upper buttocks as a subcutaneous site for treprostinil infusion in children with pulmonary artery hypertension
Authors: Ono Hiroshi , Yotani Nobuyuki , Kato Hitoshi
Published: May 2020

A 14-year-old boy was receiving subcutaneous infusions of treprostinil for pulmonary artery hypertension. Because he had severe infusion site pain in the lower abdomen, we changed his infusion site to the upper buttocks, adding some analgesics. His pain improved gradually. This change may be an effective method for reducing infusion site pain in subcutaneous treprostinil therapy, particularly in children.
Who Do You Loathe? Feelings toward Politicians vs. Ordinary People in the Opposing Party
Authors: Kingzette Jon
Published: May 2020

Scholars, the media, and ordinary people alike express alarm at the apparent loathing between Democrats and Republicans in the mass public. However, the evidence of such loathing typically comes from survey items that measure attitudes toward the Democratic and Republican Parties, rather than attitudes toward ordinary partisans. Using a nationally representative survey, I find that Democrats and Republicans have substantially more positive feelings toward ordinary people belonging to the opposing party than they do toward politicians in the opposing party and the opposing party itself. These results indicate that research relying on measures of feelings toward the opposing “Party” vastly overstates levels of partisan animosity in the American public and demonstrate the need to distinguish between attitudes toward party elites and ordinary partisans in future research.
Fear of Physical Activity, Anxiety, and Depression
Authors: Spaderna Heike , Hoffman Jeremia M. , Hellwig Susan , Brandenburg Vincent M.
Published: May 2020

Abstract. Background: Physical activity (PA) is recommended by heart failure treatment guidelines. Adherence to exercise prescriptions is low and not much is known about everyday PA in this patient group. Aims: This study describes objectively assessed everyday PA/sedentary behavior in men and women with chronic heart failure and examines associations of potential barriers for engaging in PA, namely fear of physical activity (FoPA), general anxiety, and depression, with indicators of PA and sedentary behavior. Method: In 61 outpatients with heart failure (67.5 ± 10.7 years of age) the impact of FoPA, trait anxiety, and depression on 6-day accelerometer measures was evaluated using linear regression models. Results: Sedentary behavior was prevalent in men and women alike, with lying down and sitting/standing as predominant activity classes during daytime. Men had higher PA energy expenditure (726 vs. 585 kcal/d, Cohen’s effect size d = 0.74) and walked up/down more often (0.21% vs. 0.12% of total PA, d = 0.56) than women. FoPA did not differ between sexes. FoPA, but not anxiety and depression, significantly and consistently predicted less walking up/down independent of covariates (β-values between −0.26 and −0.44, p-values < 0.024). Limitations: The self-selected sample included few women. Medical data were assessed via self-reports. Conclusion: FoPA, but not anxiety and depression, significantly and consistently predicted less walking up/down independent of covariates. These preliminary findings highlight FoPA as a barrier to everyday PA in patients with heart failure.
Comparisons as Predictors of People’s Beliefs About the	Importance of Changing Their Health Behaviors
Authors: Miller Jane E. , Windschitl Paul D. , Treat Teresa A. , Scherer Aaron M.
Published: May 2020

Abstract. The current study tested relative strengths of different comparison beliefs for predicting people’s self-assessments of whether they should increase their health-relevant behaviors (exercise, sleep, and fruit and vegetable consumption). Comparison beliefs relevant to three standards (perceived global, local, expert standards) were evaluated. Data were combined from three similar studies (total N = 744) that had a cross-sectional, within-subject design. Participants completed importance-of-change scales regarding the three health behaviors and reported comparison beliefs and absolute behavior frequencies/amounts. Results were consistent across the three behaviors. Comparison beliefs predicted ratings of importance of changing one’s behavior, even beyond what is predicted by reports of absolute behavior frequency. Expert comparisons were consistently most predictive above and beyond the absolute estimates and the other comparison standards. There was no evidence of a local dominance effect when examining local versus global comparisons. Comparison beliefs have unique utility for predicting people’s perceived importance of changing their heath behavior. The fact that expert comparisons were consistently most predictive (and local comparisons the least) may have implications for interventions designed for encouraging behavior change.
Thank You to Our 2019 Reviewers
Authors: Balikhin Michael , Ganushkina Natalia Yu , Hickey Michael P. , Kepko Larry , Liemohn Michael , Pierrard Viviane , Song Paul , Wang Yuming , Zong Qiugang
Published: May 2020

Key Points

The editors thank the 2019 peer reviewers
Ultra-accurate Duplex Sequencing for the assessment of pretreatment ABL1 kinase domain mutations in Ph+ ALL
Authors: Short Nicholas J. , Kantarjian Hagop , Kanagal-Shamanna Rashmi , Sasaki Koji , Ravandi Farhad , Cortes Jorge , Konopleva Marina , Issa Ghayas C. , Kornblau Steven M. , Garcia-Manero Guillermo , Garris Rebecca , Higgins Jake , Pratt Gabriel , Williams Lindsey N. , Valentine Charles C. , Rivera Victor M. , Pritchard Justin , Salk Jesse J. , Radich Jerald , Jabbour Elias
Published: May 2020

Mutations of ABL1 are the dominant mechanism of relapse in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). We performed highly accurate Duplex Sequencing of exons 4–10 of ABL1 on bone marrow or peripheral blood samples from 63 adult patients with previously untreated Ph + ALL who received induction with intensive chemotherapy plus a BCR-ABL1 TKI. We identified ABL1 mutations prior to BCR-ABL1 TKI exposure in 78% of patients. However, these mutations were generally present at extremely low levels (median variant allelic frequency 0.008% [range, 0.004%–3.71%] and did not clonally expand and lead to relapse in any patient, even when the pretreatment mutation was known to confer resistance to the TKI received. In relapse samples harboring a TKI-resistant ABL1 mutation, the corresponding mutation could not be detected pretreatment, despite validated sequencing sensitivity of Duplex Sequencing down to 0.005%. In samples under the selective pressure of ongoing TKI therapy, we detected low-level, emerging resistance mutations up to 5 months prior to relapse. These findings suggest that pretreatment ABL1 mutation assessment should not guide upfront TKI selection in Ph + ALL, although serial testing while on TKI therapy may allow for early detection of clinically actionable resistant clones.
Regorafenib is effective against neuroblastoma in vitro and in vivo and inhibits the RAS/MAPK, PI3K/Akt/mTOR and Fos/Jun pathways
Authors: Subramonian Divya , Phanhthilath Nikki , Rinehardt Hannah , Flynn Sean , Huo Yuchen , Zhang Jing , Messer Karen , Mo Qianxing , Huang Shixia , Lesperance Jacqueline , Zage Peter E.
Published: May 2020

Background

Regorafenib is an inhibitor of multiple kinases with aberrant expression and activity in neuroblastoma tumours that have potential roles in neuroblastoma pathogenesis.

Methods

We evaluated neuroblastoma cells treated with regorafenib for cell viability and confluence, and analysed treated cells for apoptosis and cell cycle progression. We evaluated the efficacy of regorafenib in vivo using an orthotopic xenograft model. We evaluated regorafenib-mediated inhibition of kinase targets and performed reverse-phase protein array (RPPA) analysis of neuroblastoma cells treated with regorafenib. Lastly, we evaluated the efficacy and effects of the combination of regorafenib and 13-cis-retinoic acid on intracellular signalling.

Results

Regorafenib treatment resulted in reduced neuroblastoma cell viability and confluence, with both induction of apoptosis and of cell cycle arrest. Regorafenib treatment inhibits known receptor tyrosine kinase targets RET and PDGFRβ and intracellular signalling through the RAS/MAPK, PI3K/Akt/mTOR and Fos/Jun pathways. Regorafenib is effective against neuroblastoma tumours in vivo, and the combination of regorafenib and 13-cis-retinoic acid demonstrates enhanced efficacy compared with regorafenib alone.

Conclusions

The effects of regorafenib on multiple intracellular signalling pathways and the potential additional efficacy when combined with 13-cis-retinoic acid represent opportunities to develop treatment regimens incorporating regorafenib for children with neuroblastoma.
Circular RNA circNRIP1 promotes migration and invasion in cervical cancer by sponging miR-629-3p and regulating the PTP4A1/ERK1/2 pathway
Authors: Li Xinhui , Ma Ningye , Zhang Yao , Wei Heng , Zhang Huijie , Pang Xiaoao , Li Xiang , Wu Dan , Wang Dian , Yang Zhuo , Zhang Shulan
Published: May 2020

Emerging evidence indicates that circRNAs play essential roles in tumorigenesis and development. However, the role of circRNAs in cervical cancer (CC) remains unclear. CircRNA microarrays performed on the immortal cervical cell line H8 and the cervical cancer cell line SiHa were used to identify a circRNA, termed circNRIP1 (hsa_circ_0004771), which was upregulated in SiHa. QRT-PCR confirmed that circNRIP1 was upregulated in CC tissues, where its expression was correlated with lymphovascular space invasion. Besides, both in vitro and in vivo experiments demonstrated that circNRIP1 promotes cell proliferation, migration, and invasion. Additionally, we found that miR-629-3p induced tumor suppression by regulating PTP4A1 and the ERK1/2 pathway. Finally, we confirmed that circNRIP1 exerts its effect, at least partially, by sponging miR-629-3p and thereby regulating the PTP4A1/ERK1/2 pathway. Therefore, circNRIP1 may be useful as a potential prognostic biomarker and therapeutic target in CC patients.
Phenology and related traits for wheat adaptation
Authors: Hyles Jessica , Bloomfield Maxwell T. , Hunt James R. , Trethowan Richard M. , Trevaskis Ben
Published: May 2020

Wheat is a major food crop, with around 765 million tonnes produced globally. The largest wheat producers include the European Union, China, India, Russia, United States, Canada, Pakistan, Australia, Ukraine and Argentina. Cultivation of wheat across such diverse global environments with variation in climate, biotic and abiotic stresses, requires cultivars adapted to a range of growing conditions. One intrinsic way that wheat achieves adaptation is through variation in phenology (seasonal timing of the lifecycle) and related traits (e.g., those affecting plant architecture). It is important to understand the genes that underlie this variation, and how they interact with each other, other traits and the growing environment. This review summarises the current understanding of phenology and developmental traits that adapt wheat to different environments. Examples are provided to illustrate how different combinations of alleles can facilitate breeding of wheat varieties with optimal crop performance for different growing regions or farming systems.
Hurricane-induced disturbance increases genetic diversity and population admixture of the direct-brooding isopod, Gnathia marleyi
Authors: Pagán J. Andrés , Veríssimo Ana , Sikkel Paul C. , Xavier Raquel
Published: May 2020

Severe disturbances can substantially alter eco-evolutionary processes and dynamics. While the impacts of catastrophic events on the biophysical attributes of communities are sometimes assessed, their effects on the genetic patterns of species remain poorly understood. To characterize how severe disturbances impact species at the molecular level, we examined the effects of the most energetic North Atlantic hurricane season in 50 years on the genetic diversity and structure of a dispersal-limited isopod, Gnathia marleyi. We sequenced a portion of the cytochrome oxidase I gene for 432 gnathiids, collected from six localities, ranging from western Puerto Rico to St John, US Virgin Islands. Importantly, multiple years of pre-hurricane sample collection allowed us to characterize temporal genetic patterns under undisturbed conditions and detect the changes subsequent to the 2017 hurricanes. Our results revealed no change to genetic diversity or structure for the years prior to the 2017 hurricanes, with genetic structure occurring at the local and regional levels, with three main clusters corresponding to Southwest Puerto Rico, East Puerto Rico, and the US Virgin Islands. However, directly following the 2017 hurricanes, genetic diversity increased at five of the six sampled localities. Additionally, we found a clear homogenizing effect prompted by increased shared genetic diversity among geographically distant regions and sites that resulted in substantially decreased among-region and among-site differentiation. Our work shows that severe disturbances caused by major tropical hurricanes facilitate gene-flow and increase overall genetic diversity and population admixture of dispersal limited coral reef species, potentially impacting the ecology and evolution of a key regional endemic.
Microfluidic Enrichment Barcoding (MEBarcoding): a new method for high throughput plant DNA barcoding
Authors: Gostel Morgan R. , Zúñiga Jose D. , Kress W. John , Funk Vicki A. , Puente-Lelievre Caroline
Published: May 2020

DNA barcoding is a valuable tool to support species identification with broad applications from traditional taxonomy, ecology, forensics, food analysis, and environmental science. We introduce Microfluidic Enrichment Barcoding (MEBarcoding) for plant DNA Barcoding, a cost-effective method for high-throughput DNA barcoding. MEBarcoding uses the Fluidigm Access Array to simultaneously amplify targeted regions for 48 DNA samples and hundreds of PCR primer pairs (producing up to 23,040 PCR products) during a single thermal cycling protocol. As a proof of concept, we developed a microfluidic PCR workflow using the Fluidigm Access Array and Illumina MiSeq. We tested 96 samples for each of the four primary DNA barcode loci in plants: rbcL, matK, trnH-psbA, and ITS. This workflow was used to build a reference library for 78 families and 96 genera from all major plant lineages – many currently lacking in public databases. Our results show that this technique is an efficient alternative to traditional PCR and Sanger sequencing to generate large amounts of plant DNA barcodes and build more comprehensive barcode databases.
Temporal rate is not a distinct perceptual metric
Authors: Motala Aysha , Heron James , McGraw Paul V. , Roach Neil W. , Whitaker David
Published: May 2020

Sensory adaptation experiments have revealed the existence of ‘rate after-effects’ - adapting to a relatively fast rate makes an intermediate test rate feel slow, and adapting to a slow rate makes the same moderate test rate feel fast. The present work aims to deconstruct the concept of rate and clarify how exactly the brain processes a regular sequence of sensory signals. We ask whether rate forms a distinct perceptual metric, or whether it is simply the perceptual aggregate of the intervals between its component signals. Subjects were exposed to auditory or visual temporal rates (a ‘slow’ rate of 1.5 Hz and a ‘fast’ rate of 6 Hz), before being tested with single unfilled intervals of varying durations. Results show adapting to a given rate strongly influences the perceived duration of a single empty interval. This effect is robust across both interval reproduction and duration discrimination judgments. These findings challenge our understanding of rate perception. Specifically, they suggest that contrary to some previous assertions, the perception of sequence rate is strongly influenced by the perception of the sequence’s component duration intervals.
Author Correction: De novo design of RNA-binding proteins with a prion-like domain related to ALS/FTD proteinopathies
Authors: Mitsuhashi Kana , Ito Daisuke , Mashima Kyoko , Oyama Munenori , Takahashi Shinichi , Suzuki Norihiro
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Aspartate/asparagine-β-hydroxylase: a high-throughput mass spectrometric assay for discovery of small molecule inhibitors
Authors: Brewitz Lennart , Tumber Anthony , Pfeffer Inga , McDonough Michael A. , Schofield Christopher J.
Published: May 2020

The human 2-oxoglutarate dependent oxygenase aspartate/asparagine-β-hydroxylase (AspH) catalyses the hydroxylation of Asp/Asn-residues in epidermal growth factor-like domains (EGFDs). AspH is upregulated on the surface of malign cancer cells; increased AspH levels correlate with tumour invasiveness. Due to a lack of efficient assays to monitor the activity of isolated AspH, there are few reports of studies aimed at identifying small-molecule AspH inhibitors. Recently, it was reported that AspH substrates have a non-canonical EGFD disulfide pattern. Here we report that a stable synthetic thioether mimic of AspH substrates can be employed in solid phase extraction mass spectrometry based high-throughput AspH inhibition assays which are of excellent robustness, as indicated by high Z’-factors and good signal-to-noise/background ratios. The AspH inhibition assay was applied to screen approximately 1500 bioactive small-molecules, including natural products and active pharmaceutical ingredients of approved human therapeutics. Potent AspH inhibitors were identified from both compound classes. Our AspH inhibition assay should enable the development of potent and selective small-molecule AspH inhibitors and contribute towards the development of safer inhibitors for other 2OG oxygenases, e.g. screens of the hypoxia-inducible factor prolyl-hydroxylase inhibitors revealed that vadadustat inhibits AspH with moderate potency.
Temporal variation in daily temperature minima in coral reefs of Nanwan Bay, Southern Taiwan
Authors: Lee I-Huan , Fan Tung-Yung , Fu Ke-Hsien , Ko Dong Shan
Published: May 2020

Temporal variation in seawater temperature plays a crucial role in coral reef ecology. Nanwan Bay, Southern Taiwan is home to well-developed coral reefs, which frequently experience cold-water intrusions caused by internal wave-induced upwelling, that manifest in distinct daily temperature minima. These temperature minima and their associated sources were studied by recording in situ bottom temperatures and sea levels observed at depths of 5 and 30 m from May 2007 to September 2008. These data were then compared to the East Asian Seas Nowcast/Forecast System, and it was found that daily temperature minima presented large variations with magnitudes of 2–3 °C over periods from days to months. It was further demonstrated that the cold-water intrusions may have originated from depths of ~100 m and were strongly affected by westward propagating mesoscale eddies from the Pacific basin. An impinging warm anticyclonic eddy in July 2007 may have combined with the El Niño, resulting in temperatures surpassing 29 °C and degree heating days >4.0 °C-days at both depths, which were coincidental with a mass coral bleaching event. This eddy’s impact was additionally evident in high correlations between daily temperature minima and residual sea levels, suggesting that mesoscale eddies alter stratification, substantially influence temperature variation, and play important roles in understanding ecological processes on coral reefs.
Evidence of Biorealistic Synaptic Behavior in Diffusive Li-based Two-terminal Resistive Switching Devices
Authors: Ioannou Panagiotis S. , Kyriakides Evripides , Schneegans Olivier , Giapintzakis John
Published: May 2020

Following the recent advances in artificial synaptic devices and the renewed interest regarding artificial intelligence and neuromorphic computing, a new two-terminal resistive switching device, based on mobile Li+ ions is hereby explored. Emulation of neural functionalities in a biorealistic manner has been recently implemented through the use of synaptic devices with diffusive dynamics. Mimicking of the spontaneous synaptic weight relaxation of neuron cells, which is regulated by the concentration kinetics of positively charged ions like Ca2+, is facilitated through the conductance relaxation of such diffusive devices. Adopting a battery-like architecture, using LiCoO2 as a resistive switching cathode layer, SiOx as an electrolyte and TiO2 as an anode, Au/LiCoO2/SiOx/TiO2/p++-Si two-terminal devices have been fabricated. Analog conductance modulation, via voltage-driven regulation of Li+ ion concentration in the cathode and anode layers, along with current rectification and nanobattery effects are reported. Furthermore, evidence is provided for biorealistic synaptic behavior, manifested as paired pulse facilitation based on the summation of excitatory post-synaptic currents and spike-timing-dependent plasticity, which are governed by the Li+ ion concentration and its relaxation dynamics.
The false cleanerfish relies on aggressive mimicry to bite fish fins when benthic foods are scarce in their local habitat
Authors: Fujisawa Misaki , Sakai Yoichi , Kuwamura Tetsuo
Published: May 2020

The false cleanerfish, Aspidontus taeniatus (Blenniidae), is known for its morphological resemblance to the bluestreak cleaner wrasse Labroides dimidiatus (Labridae). It has been suggested that A. taeniatus, which acts as a mimic, can easily bite the fins of other fishes that are deceived into requesting cleaning from it or allowing it to approach them. In fact, A. taeniatus frequently utilises benthic food items, such as damselfish eggs, the Christmas tree worm Spirobranchus giganteus, and the boring clam Tridacna crocea. Although geographical variation in the reliance on aggressive mimicry (fin biting) has been reported, the factors have not been determined. We hypothesised that one of the factors is the abundance of benthic food items. To examine our hypothesis, we compared the feeding behaviour of A. taeniatus at two locations showing contrasting abundances of benthic food items in Okinawa, southern Japan. The frequency of fin biting by the small A. taeniatus in Ishigaki Island, where S. giganteus and T. crocea were very rare, was significantly higher than that in Sesoko Island, where the two food items were abundant. We conclude that the importance of aggressive mimicry in A. taeniatus varies depending on local food conditions.
SIRT3 and GCN5L regulation of NADP+- and NADPH-driven reactions of mitochondrial isocitrate dehydrogenase IDH2
Authors: Smolková Katarína , Špačková Jitka , Gotvaldová Klára , Dvořák Aleš , Křenková Alena , Hubálek Martin , Holendová Blanka , Vítek Libor , Ježek Petr
Published: May 2020

Wild type mitochondrial isocitrate dehydrogenase (IDH2) was previously reported to produce oncometabolite 2-hydroxyglutarate (2HG). Besides, mitochondrial deacetylase SIRT3 has been shown to regulate the oxidative function of IDH2. However, regulation of 2HG formation by SIRT3-mediated deacetylation was not investigated yet. We aimed to study mitochondrial IDH2 function in response to acetylation and deacetylation, and focus specifically on 2HG production by IDH2. We used acetylation surrogate mutant of IDH2 K413Q and assayed enzyme kinetics of oxidative decarboxylation of isocitrate, 2HG production by the enzyme, and 2HG production in cells. The purified IDH2 K413Q exhibited lower oxidative reaction rates than IDH2 WT. 2HG production by IDH2 K413Q was largely diminished at the enzymatic and cellular level, and knockdown of SIRT3 also inhibited 2HG production by IDH2. Contrary, the expression of putative mitochondrial acetylase GCN5L likely does not target IDH2. Using mass spectroscopy, we further identified lysine residues within IDH2, which are the substrates of SIRT3. In summary, we demonstrate that 2HG levels arise from non-mutant IDH2 reductive function and decrease with increasing acetylation level. The newly identified lysine residues might apply in regulation of IDH2 function in response to metabolic perturbations occurring in cancer cells, such as glucose-free conditions.
Use of synergistic mixture of chelating agents for in situ LDH growth on the surface of PEO-treated AZ91
Authors: Petrova E. , Serdechnova M. , Shulha T. , Lamaka S. V. , Wieland D. C. F. , Karlova P. , Blawert C. , Starykevich M. , Zheludkevich M. L.
Published: May 2020

The principal possibility to grow layered double hydroxide (LDH) at ambient pressure on plasma electrolytic oxidation (PEO) treated magnesium alloy AZ91 in the presence of chelating agents is demonstrated for the first time. It avoids hydrothermal autoclave conditions, which strongly limit wide industrial application of such coating systems, and the presence of carbonate ions in the electrolyte, which lead to the formation of “passive” non-functionalizable LDH. A combination of chelating agents (sodium diethylenetriamine-pentaacetate (DTPA) and salicylate) were introduced to the treatment solution. The role of each additive and the influence of treatment bath composition on the LDH formation processes are discussed. A synergistic effect of DTPA and salicylate during LDH formation is discovered and its possible explanation is proposed.
Phase estimation algorithm for the multibeam optical metrology
Authors: Zemlyanov V. V. , Kirsanov N. S. , Perelshtein M. R. , Lykov D. I. , Misochko O. V. , Lebedev M. V. , Vinokur V. M. , Lesovik G. B.
Published: May 2020

Unitary Fourier transform lies at the core of the multitudinous computational and metrological algorithms. Here we show experimentally how the unitary Fourier transform-based phase estimation protocol, used namely in quantum metrology, can be translated into the classical linear optical framework. The developed setup made of beam splitters, mirrors and phase shifters demonstrates how the classical coherence, similarly to the quantum coherence, poses a resource for obtaining information about the measurable physical quantities. Our study opens route to the reliable implementation of the small-scale unitary algorithms on path-encoded qudits, thus establishing an easily accessible platform for unitary computation.
A Gilbert syndrome-associated haplotype protects against fatty liver disease in humanized transgenic mice
Authors: Landerer Steffen , Kalthoff Sandra , Paulusch Stefan , Strassburg Christian P.
Published: May 2020

UDP-glucuronosyltransferases 1 A (UGT1A) enzymes are capable of detoxifying a broad range of endo- and xenobiotic compounds, which contributes to antioxidative effects, modulation of inflammation and cytoprotection. In the presence of low-function genetic UGT1A variants fibrosis development is increased in various diseases. This study aimed to examine the role of common UGT1A polymorphisms in NASH. Therefore, htgUGT1A-WT mice and htgUGT1A-SNP mice (carrying a common human haplotype present in 10% of the white population) were fed a high-fat Paigen diet for 24 weeks. Serum aminotransferase activities, hepatic triglycerides, fibrosis development and UGT1A expression were assessed. Microscopic examination revealed higher hepatic fat deposition and a significant induction of UGT1A gene expression in htgUGT1A-WT mice. In agreement with these observations, lower serum aminotransferase activities and lower expression levels of fibrosis-related genes were measured in htgUGT1A-SNP mice. This was accompanied by reduced PPARα protein levels in htgUGT1A-WT but not in SNP mice. Our data demonstrate a protective effect of a UGT1A SNP haplotype, leading to milder hepatic steatosis and NASH. Higher PPARα protein levels in animals with impaired UGT1A activity are the likely result of reduced glucuronidation of ligands involved in PPARα-mediated fatty acid oxidation and may lead to the observed protection in htgUGT1A-SNP mice.
Poor neural and perceptual phoneme discrimination during acoustic variation in dyslexia
Authors: Virtala P. , Talola S. , Partanen E. , Kujala T.
Published: May 2020

Whereas natural acoustic variation in speech does not compromise phoneme discrimination in healthy adults, it was hypothesized to be a challenge for developmental dyslexics. We investigated dyslexics’ neural and perceptual discrimination of native language phonemes during acoustic variation. Dyslexics and non-dyslexics heard /æ/ and /i/ phonemes in a context with fo variation and then in a context without it. Mismatch negativity (MMN) and P3a responses to phoneme changes were recorded with electroencephalogram to compare groups during ignore and attentive listening. Perceptual phoneme discrimination in the variable context was evaluated with hit-ratios and reaction times. MMN/N2bs were diminished in dyslexics in the variable context. Hit-ratios were smaller in dyslexics than controls. MMNs did not differ between groups in the context without variation. These results suggest that even distinctive vowels are challenging to discriminate for dyslexics when the context resembles natural variability of speech. This most likely reflects poor categorical perception of phonemes in dyslexics. Difficulties to detect linguistically relevant invariant information during acoustic variation in speech may contribute to dyslexics’ deficits in forming native language phoneme representations during infancy. Future studies should acknowledge that simple experimental paradigms with repetitive stimuli can be insensitive to dyslexics’ speech processing deficits.
Repression of the lysogenic PR promoter in bacteriophage TP901-1 through binding of a CI-MOR complex to a composite OM-OR operator
Authors: Pedersen Margit , Neergaard Jesper Tvenge , Cassias Johan , Rasmussen Kim Krighaar , Lo Leggio Leila , Sneppen Kim , Hammer Karin , Kilstrup Mogens
Published: May 2020

A functional genetic switch from the lactococcal bacteriophage TP901-1, deciding which of two divergently transcribing promoters becomes most active and allows this bi-stable decision to be inherited in future generations requires a DNA region of less than 1 kb. The fragment encodes two repressors, CI and MOR, transcribed from the PR and PL promoters respectively. CI can repress the transcription of the mor gene at three operator sites (OR, OL, and OD), leading to the immune state. Repression of the cI gene, leading to the lytic (anti-immune) state, requires interaction between CI and MOR by an unknown mechanism, but involving a CI:MOR complex. A consensus for putative MOR binding sites (OM sites), and a common topology of three OM sites adjacent to the OR motif was here identified in diverse phage switches that encode CI and MOR homologs, in a search for DNA sequences similar to the TP901-1 switch. The OR site and all putative OM sites are important for establishment of the anti-immune repression of PR, and a putative DNA binding motif in MOR is needed for establishment of the anti-immune state. Direct evidence for binding between CI and MOR is here shown by pull-down experiments, chemical crosslinking, and size exclusion chromatography. The results are consistent with two possible models for establishment of the anti-immune repression of cI expression at the PR promoter.
Cost-effectiveness analysis of GnRH-agonist long-protocol and GnRH-antagonist protocol for in vitro fertilization
Authors: Jing Miaomiao , Lin Chenxi , Zhu Wenjun , Tu Xiaoyu , Chen Qi , Wang Xiufang , Zheng Youbing , Zhang Runju
Published: May 2020

The gonadotropin releasing hormone agonist (GnRH-a) long-protocols and the GnRH-antagonist protocols are two commonly used protocols for in vitro fertilization (IVF), but their cost-effectiveness has not been studied, especially in China. A retrospective study involving 1638 individuals in GnRH-a long-protocol and 621 in GnRH-antagonist protocol were conducted and a decision tree model analysis was used to analyze the cost-effectiveness. Both direct and indirect costs were calculated. As a result, during the fresh embryo transplantation cycles, there was no significant difference in the rate of ongoing pregnancy between the two protocols, the average cost of per ongoing pregnancy in the GnRH-antagonist protocol was $ 16970.85, and that in the GnRH-agonist long-protocol was $19902.24. The probability of cumulative ongoing pregnancy per start cycle was estimated at 60.65% for the GnRH-antagonist protocol and 71.6% for the GnRH-agonist long-protocol (P < 0.01). Considering the cumulative ongoing pregnancy rate, the mean costs per ongoing pregnancy were estimated at $8176.76 and at $7595.28 with GnRH-antagonist protocol and GnRH-agonist long protocol, respectively. In conclusion, in fresh embryo transplantation cycle, the GnRH-antagonist protocol has economic advantage. However, the GnRH-agonist long protocol is more cost effective considering the cumulative ongoing pregnancy rate in the fresh embryo and frozen embryo transplantation cycles.
Estimation of trophic niches in myrmecophagous spider predators
Authors: Dušátková Lenka Petráková , Pekár Stano , Michálek Ondřej , Líznarová Eva , Symondson William O. C.
Published: May 2020

Among spiders, taxonomically the most diversified group of terrestrial predators, only a few species are stenophagous and feed on ants. The levels of stenophagy and ant-specialisation vary among such species. To investigate whether stenophagy is only a result of a local specialisation both fundamental and realised trophic niches need to be estimated. Here we investigated trophic niches in three closely-related spider species from the family Gnaphosidae (Callilepis nocturna, C. schuszteri, Nomisia exornata) with different levels of myrmecophagy. Acceptance experiments were used to estimate fundamental trophic niches and molecular methods to estimate realised trophic niches. For the latter two PCR primer sets were used as these can affect the niche breadth estimates. The general invertebrate ZBJ primers were not appropriate for detecting ant DNA as they revealed very few prey types, therefore ant-specific primers were used. The cut-off threshold for erroneous MOTUs was identified as 0.005% of the total number of valid sequences, at individual predator level it was 0.05%. The fundamental trophic niche of Callilepis species included mainly ants, while that of N. exornata included many different prey types. The realised trophic niche in Callilepis species was similar to its fundamental niche but in N. exornata the fundamental niche was wider than realised niche. The results show that Callilepis species are ant-eating (specialised) stenophagous predators, catching mainly Formicinae ants, while N. exornata is an ant-eating euryphagous predator catching mainly Myrmicinae ants.