bluuebunny/crossref_metadata_2025 huggingface dataset:
Brahms, Beethoven, and a Reassessment of the Famous Footsteps
Authors: Avins Styra
Published: January 2021

To speak of Brahms and Beethoven in the same breath is almost a cliché: Brahms was intimately conscious of Beethoven's music from early youth. This article describes the details of his youthful involvement, the compositions he had in his repertoire as well as those other works which had a powerful effect on his development. By age 20, Brahms was frequently compared to Beethoven by people who met him or heard him play. My interest is in the way he was influenced by Beethoven and the manner in which he eventually found his own voice.

The compositional history of his First Symphony provides the primary focus: its long gestation, and the alleged quote by Brahms given in Max Kalbeck's massive biography: ‘I'll never write a symphony, you have no idea what it feels like … to hear the footsteps of a giant behind one’. The reference is presumably to Beethoven, but there exists no corroborating evidence that Brahms ever said those words. They gained credence as one writer after another simply accepted Kalbeck's word. Yet substantial evidence exists that in writing his biography, Kalbeck distorted and even invented ‘facts’ when it suited his purposes, including a specific instance dealing with writing a symphony.

An alternative view of the symphony's long gestation is based on a view of Brahms's compositional history. He wrote for musical forces he knew at first hand, and only from 1872 to 1875 did he have command of an orchestra. Intriguingly, while fulfilling the contemporary accepted demands of a symphony after Beethoven, Brahms devised an unusual strategy for the final movement, the basis of its great success.
European political parties’ complicity in democratic backsliding
Authors: WOLKENSTEIN FABIO
Published: January 2021

This article discusses the contribution of European political parties to democratic backsliding. It focuses on the European People’s Party’s efforts to protect the Hungarian government, and the European Conservatives and Reformists party’s permissive acceptance of the Polish government’s attacks on democracy and the rule of law, analysing these patterns of behaviour as a form of complicity in democratic backsliding. In a second step, the article examines the existing possibilities and normative justification for sanctioning European political parties that make a complicit contribution to democratic backsliding.
The Revival of Quantification: Reflections on Old New Histories
Authors: Ruggles Steven
Published: January 2021

Quantitative historical analysis in the United States surged in three distinct waves. The first quantitative wave occurred as part of the “New History” that blossomed in the early twentieth century and disappeared in the 1940s and 1950s with the rise of consensus history. The second wave thrived from the 1960s to the 1980s during the ascendance of the New Economic History, the New Political History, and the New Social History, and died out during the “cultural turn” of the late twentieth century. The third wave of historical quantification—which I call the revival of quantification—emerged in the second decade of the twenty-first century and is still underway. I describe characteristics of each wave and discuss the historiographical context of the ebb and flow of quantification in history.
Graphical analysis for phenome-wide causal discovery in genotyped population-scale biobanks
Authors: Amar David , Sinnott-Armstrong Nasa , Ashley Euan A. , Rivas Manuel A.
Published: January 2021

Causal inference via Mendelian randomization requires making strong assumptions about horizontal pleiotropy, where genetic instruments are connected to the outcome not only through the exposure. Here, we present causal Graphical Analysis Using Genetics (cGAUGE), a pipeline that overcomes these limitations using instrument filters with provable properties. This is achievable by identifying conditional independencies while examining multiple traits. cGAUGE also uses ExSep (Exposure-based Separation), a novel test for the existence of causal pathways that does not require selecting instruments. In simulated data we illustrate how cGAUGE can reduce the empirical false discovery rate by up to 30%, while retaining the majority of true discoveries. On 96 complex traits from 337,198 subjects from the UK Biobank, our results cover expected causal links and many new ones that were previously suggested by correlation-based observational studies. Notably, we identify multiple risk factors for cardiovascular disease, including red blood cell distribution width.
Mixed halide perovskites for spectrally stable and high-efficiency blue light-emitting diodes
Authors: Karlsson Max , Yi Ziyue , Reichert Sebastian , Luo Xiyu , Lin Weihua , Zhang Zeyu , Bao Chunxiong , Zhang Rui , Bai Sai , Zheng Guanhaojie , Teng Pengpeng , Duan Lian , Lu Yue , Zheng Kaibo , Pullerits Tönu , Deibel Carsten , Xu Weidong , Friend Richard , Gao Feng
Published: January 2021

Bright and efficient blue emission is key to further development of metal halide perovskite light-emitting diodes. Although modifying bromide/chloride composition is straightforward to achieve blue emission, practical implementation of this strategy has been challenging due to poor colour stability and severe photoluminescence quenching. Both detrimental effects become increasingly prominent in perovskites with the high chloride content needed to produce blue emission. Here, we solve these critical challenges in mixed halide perovskites and demonstrate spectrally stable blue perovskite light-emitting diodes over a wide range of emission wavelengths from 490 to 451 nanometres. The emission colour is directly tuned by modifying the halide composition. Particularly, our blue and deep-blue light-emitting diodes based on three-dimensional perovskites show high EQE values of 11.0% and 5.5% with emission peaks at 477 and 467 nm, respectively. These achievements are enabled by a vapour-assisted crystallization technique, which largely mitigates local compositional heterogeneity and ion migration.
A DNA origami-based aptamer nanoarray for potent and reversible anticoagulation in hemodialysis
Authors: Zhao Shuai , Tian Run , Wu Jun , Liu Shaoli , Wang Yuanning , Wen Meng , Shang Yingxu , Liu Qing , Li Yan , Guo Ying , Wang Zhaoran , Wang Ting , Zhao Yujing , Zhao Huiru , Cao Hui , Su Yu , Sun Jiashu , Jiang Qiao , Ding Baoquan
Published: January 2021

Effective and safe hemodialysis is essential for patients with acute kidney injury and chronic renal failures. However, the development of effective anticoagulant agents with safe antidotes for use during hemodialysis has proven challenging. Here, we describe DNA origami-based assemblies that enable the inhibition of thrombin activity and thrombus formation. Two different thrombin-binding aptamers decorated DNA origami initiates protein recognition and inhibition, exhibiting enhanced anticoagulation in human plasma, fresh whole blood and a murine model. In a dialyzer-containing extracorporeal circuit that mimicked clinical hemodialysis, the origami-based aptamer nanoarray effectively prevented thrombosis formation. Oligonucleotides containing sequences complementary to the thrombin-binding aptamers can efficiently neutralize the anticoagulant effects. The nanoarray is safe and immunologically inert in healthy mice, eliciting no detectable changes in liver and kidney functions or serum cytokine concentration. This DNA origami-based nanoagent represents a promising anticoagulant platform for the hemodialysis treatment of renal diseases.
Spontaneous mutations in the single TTN gene represent high tumor mutation burden
Authors: Oh Ji-Hye , Jang Se Jin , Kim Jihun , Sohn Insuk , Lee Ji-Young , Cho Eun Jeong , Chun Sung-Min , Sung Chang Ohk
Published: January 2021

Tumor mutation burden (TMB) is an emerging biomarker, whose calculation requires targeted sequencing of many genes. We investigated if the measurement of mutation counts within a single gene is representative of TMB. Whole-exome sequencing (WES) data from the pan-cancer cohort (n = 10,224) of TCGA, and targeted sequencing (tNGS) and TTN gene sequencing from 24 colorectal cancer samples (AMC cohort) were analyzed. TTN was identified as the most frequently mutated gene within the pan-cancer cohort, and its mutation number best correlated with TMB assessed by WES (rho = 0.917, p < 2.2e-16). Colorectal cancer was one of good candidates for the application of this diagnostic model of TTN-TMB, and the correlation coefficients were 0.936 and 0.92 for TMB by WES and TMB by tNGS, respectively. Higher than expected TTN mutation frequencies observed in other FLAGS (FrequentLy mutAted GeneS) are associated with late replication time. Diagnostic accuracy for high TMB group did not differ between TTN-TMB and TMB assessed by tNGS. Classification modeling by machine learning using TTN-TMB for MSI-H diagnosis was constructed, and the diagnostic accuracy was 0.873 by area under the curve in external validation. TTN mutation was enriched in samples possessing high immunostimulatory signatures. We suggest that the mutation load within TTN represents high TMB status.
Imprinting methylation predicts hippocampal volumes and hyperintensities and the change with age in later life
Authors: Lorgen-Ritchie Marlene , Murray Alison D. , Staff Roger , Ferguson-Smith Anne C. , Richards Marcus , Horgan Graham W. , Phillips Louise H. , Hoad Gwen , McNeil Chris , Ribeiro Antonio , Haggarty Paul
Published: January 2021

Epigenetic imprinting is important for neurogenesis and brain function. Hippocampal volumes and brain hyperintensities in late life have been associated with early life circumstances. Epigenetic imprinting may underpin these associations. Methylation was measured at 982 sites in 13 imprinted locations in blood samples from a longitudinal cohort by bisulphite amplicon sequencing. Hippocampal volumes and hyperintensities were determined at age 64y and 72y using MRI. Hyperintensities were determined in white matter, grey matter and infratentorial regions. Permutation methods were used to adjust for multiple testing. At 64y, H19/IGF2 and NESPAS methylation predicted hippocampal volumes. PEG3 predicted hyperintensities in hippocampal grey matter, and white matter. GNASXL predicted grey matter hyperintensities. Changes with age were predicted for hippocampal volume (MEST1, KvDMR, L3MBTL, GNASXL), white matter (MEST1, PEG3) and hippocampal grey matter hyperintensities (MCTS2, GNASXL, NESPAS, L3MBTL, MCTS2, SNRPN, MEST1). Including childhood cognitive ability, years in education, or socioeconomic status as additional explanatory variables in regression analyses did not change the overall findings. Imprinting methylation in multiple genes predicts brain structures, and their change over time. These findings are potentially relevant to the development of novel tests of brain structure and function across the life-course, strategies to improve cognitive outcomes, and our understanding of early influences on brain development and function.
A field investigation of the relationship between rotating shifts, sleep, mental health and physical activity of Australian paramedics
Authors: Khan Wahaj Anwar A. , Jackson Melinda L. , Kennedy Gerard A. , Conduit Russell
Published: January 2021

Paramedics working on a rotating shift are at an increased risk of developing chronic health issues due to continuous circadian rhythm disruption. The acute effects of shift rotation and objectively measured sleep have rarely been reported in paramedics. This study investigated the relationships between a rotating shift schedule and sleep (using actigraphy), subjective reports of sleepiness, mood, stress and fatigue. Galvanic Skin Response, energy expenditure and physical activity (BodyMedia SenseWear Armband) were also recorded across the shift schedule. Paramedics were monitored for a period of eight consecutive days across pre-shift, day shift, night shift, and 2 days off. Fifteen paramedics (M age = 39.5 and SD = 10.7 years) who worked rotational shifts experienced sleep restriction during night shift compared to pre-shift, day shift and days off (p < 0.001). Night shift was also associated with higher levels of stress (p < 0.05), fatigue (p < 0.05), and sleepiness (p < 0.05). One day off was related to a return to pre-shift functioning. Such shift-related issues have a compounding negative impact on an already stressful occupation with high rates of physical and mental health issues. Therefore, there is an urgent need to investigate methods to reduce rotating shift burden on the health of paramedics. This could be through further research aimed at providing recommendations for shift work schedules with sufficient periods for sleep and recovery from stress.
The impact of injury on apparent survival of whale sharks (Rhincodon typus) in South Ari Atoll Marine Protected Area, Maldives
Authors: Harvey-Carroll Jessica , Stewart Joshua D. , Carroll Daire , Mohamed Basith , Shameel Ibrahim , Zareer Irthisham H. , Araujo Gonzalo , Rees Richard
Published: January 2021

The whale shark (Rhincodon typus) is an endangered species with a declining global population. The South Ari Atoll Marine Protected Area (SAMPA), Maldives, is one of few locations globally where year-long residency of individuals occurs. This SAMPA aggregation appears to consist almost exclusively of immature males. Due to its year-round residency, this local aggregation is subjected to a high degree of tourism pressure. This ecotourism contributes to the high level of interest and protection offered to whale sharks by the local community. Unfortunately, if regulations are not followed or enforced, tourism can bring with it major stressors, such as accidental injuries. We used POPAN capture-mark-recapture models and lagged identification rate analysis to assess the effect of major injuries on whale shark residency within SAMPA. Injuries may be obtained outside SAMPA. We found individuals with major injuries had a higher apparent survival in the area than those without. Lagged identification rates also demonstrated that sharks with major injuries are more likely to return to the area. We suggest that major injuries result in sharks prolonging their time in the developmental habitat. These findings have implications for individual fitness and the population viability of this endangered species. We propose targeted conservation strategies be considered to protect sharks from further injury. Based on the presented spatio-temporal distributions of sharks, and current local knowledge of sighting patterns, speed limit zones and propeller-exclusion zones should be implemented and enforced. If carried out alongside tourist education, these measures will contribute to the protection of whale sharks within SAMPA and beyond. Furthermore, our results can aid research direction, alongside regulation and enforcement development, at similar sites worldwide.
Cognitive impairment and levodopa induced dyskinesia in Parkinson’s disease: a longitudinal study from the PACOS cohort
Authors: Luca Antonina , Monastero Roberto , Baschi Roberta , Cicero Calogero Edoardo , Mostile Giovanni , Davì Marco , Restivo Vincenzo , Zappia Mario , Nicoletti Alessandra
Published: January 2021

Aim of the study was to evaluate possible associations between cognitive dysfunctions and development of Levodopa Induced Dyskinesia (LID). PD patients from the Parkinson’s disease Cognitive impairment Study cohort who underwent a baseline and follow-up neuropsychological evaluations were enrolled. Mild Cognitive Impairment (PD-MCI) was diagnosed according to MDS level II criteria. The following cognitive domains were evaluated: episodic memory, attention, executive function, visuo-spatial function and language. A domain was considered as impaired when the subject scored 2 standard deviation below normality cut-off values in at least one test for each domain. Levodopa equivalent dose, UPDRS-ME and LID were recorded at baseline and follow-up. To identify possible neuropsychological predictors associated with the probability of LID development at follow-up, Cox proportional-hazards regression model was used. Out of 139 PD patients enrolled (87 men, mean age 65.7 ± 9.4), 18 (12.9%) were dyskinetic at baseline. Out of 121 patients non-dyskinetic at baseline, 22 (18.1%) developed LID at follow-up. The impairment of the attention and executive domains strongly predicted the development of LID (HR 4.45;95%CI 1.49–13.23 and HR 3.46; 95%CI 1.26–9.48 respectively). Impairment of the attention and executive domains increased the risk of dyskinesia reflecting the alteration of common cortical network.
Prediction of dengue outbreak in Selangor Malaysia using machine learning techniques
Authors: Salim Nurul Azam Mohd , Wah Yap Bee , Reeves Caitlynn , Smith Madison , Yaacob Wan Fairos Wan , Mudin Rose Nani , Dapari Rahmat , Sapri Nik Nur Fatin Fatihah , Haque Ubydul
Published: January 2021

Dengue fever is a mosquito-borne disease that affects nearly 3.9 billion people globally. Dengue remains endemic in Malaysia since its outbreak in the 1980’s, with its highest concentration of cases in the state of Selangor. Predictors of dengue fever outbreaks could provide timely information for health officials to implement preventative actions. In this study, five districts in Selangor, Malaysia, that demonstrated the highest incidence of dengue fever from 2013 to 2017 were evaluated for the best machine learning model to predict Dengue outbreaks. Climate variables such as temperature, wind speed, humidity and rainfall were used in each model. Based on results, the SVM (linear kernel) exhibited the best prediction performance (Accuracy = 70%, Sensitivity = 14%, Specificity = 95%, Precision = 56%). However, the sensitivity for SVM (linear) for the testing sample increased up to 63.54% compared to 14.4% for imbalanced data (original data). The week-of-the-year was the most important predictor in the SVM model. This study exemplifies that machine learning has respectable potential for the prediction of dengue outbreaks. Future research should consider boosting, or using, nature inspired algorithms to develop a dengue prediction model.
Resonance and antiresonance in Raman scattering in GaSe and InSe crystals
Authors: Osiekowicz M. , Staszczuk D. , Olkowska-Pucko K. , Kipczak Ł. , Grzeszczyk M. , Zinkiewicz M. , Nogajewski K. , Kudrynskyi Z. R. , Kovalyuk Z. D. , Patané A. , Babiński A. , Molas M. R.
Published: January 2021

The temperature effect on the Raman scattering efficiency is investigated in $$\varepsilon$$
ε
-GaSe and $$\gamma$$
γ
-InSe crystals. We found that varying the temperature over a broad range from 5 to 350 K permits to achieve both the resonant conditions and the antiresonance behaviour in Raman scattering of the studied materials. The resonant conditions of Raman scattering are observed at about 270 K under the 1.96 eV excitation for GaSe due to the energy proximity of the optical band gap. In the case of InSe, the resonant Raman spectra are apparent at about 50 and 270 K under correspondingly the 2.41 eV and 2.54 eV excitations as a result of the energy proximity of the so-called B transition. Interestingly, the observed resonances for both materials are followed by an antiresonance behaviour noticeable at higher temperatures than the detected resonances. The significant variations of phonon-modes intensities can be explained in terms of electron-phonon coupling and quantum interference of contributions from different points of the Brillouin zone.
Plasma protein expression profiles, cardiovascular disease, and religious struggles among South Asians in the MASALA study
Authors: Ngo Long H. , Austin Argentieri M. , Dillon Simon T. , Kent Blake Victor , Kanaya Alka M. , Shields Alexandra E. , Libermann Towia A.
Published: January 2021

Blood protein concentrations are clinically useful, predictive biomarkers of cardiovascular disease (CVD). Despite a higher burden of CVD among U.S. South Asians, no CVD-related proteomics study has been conducted in this sub-population. The aim of this study is to investigate the associations between plasma protein levels and CVD incidence, and to assess the potential influence of religiosity/spirituality (R/S) on significant protein-CVD associations, in South Asians from the MASALA Study. We used a nested case–control design of 50 participants with incident CVD and 50 sex- and age-matched controls. Plasma samples were analyzed by SOMAscan for expression of 1305 proteins. Multivariable logistic regression models and model selection using Akaike Information Criteria were performed on the proteins and clinical covariates, with further effect modification analyses conducted to assess the influence of R/S measures on significant associations between proteins and incident CVD events. We identified 36 proteins that were significantly expressed differentially among CVD cases compared to matched controls. These proteins are involved in immune cell recruitment, atherosclerosis, endothelial cell differentiation, and vascularization. A final multivariable model found three proteins (Contactin-5 [CNTN5], Low affinity immunoglobulin gamma Fc region receptor II-a [FCGR2A], and Complement factor B [CFB]) associated with incident CVD after adjustment for diabetes (AUC = 0.82). Religious struggles that exacerbate the adverse impact of stressful life events, significantly modified the effect of Contactin-5 and Complement factor B on risk of CVD. Our research is this first assessment of the relationship between protein concentrations and risk of CVD in a South Asian sample. Further research is needed to understand patterns of proteomic profiles across diverse ethnic communities, and the influence of resources for resiliency on proteomic signatures and ultimately, risk of CVD.
Incorporating human mobility data improves forecasts of Dengue fever in Thailand
Authors: Kiang Mathew V. , Santillana Mauricio , Chen Jarvis T. , Onnela Jukka-Pekka , Krieger Nancy , Engø-Monsen Kenth , Ekapirat Nattwut , Areechokchai Darin , Prempree Preecha , Maude Richard J. , Buckee Caroline O.
Published: January 2021

Over 390 million people worldwide are infected with dengue fever each year. In the absence of an effective vaccine for general use, national control programs must rely on hospital readiness and targeted vector control to prepare for epidemics, so accurate forecasting remains an important goal. Many dengue forecasting approaches have used environmental data linked to mosquito ecology to predict when epidemics will occur, but these have had mixed results. Conversely, human mobility, an important driver in the spatial spread of infection, is often ignored. Here we compare time-series forecasts of dengue fever in Thailand, integrating epidemiological data with mobility models generated from mobile phone data. We show that geographically-distant provinces strongly connected by human travel have more highly correlated dengue incidence than weakly connected provinces of the same distance, and that incorporating mobility data improves traditional time-series forecasting approaches. Notably, no single model or class of model always outperformed others. We propose an adaptive, mosaic forecasting approach for early warning systems.
Run-off election-based decision method for the training and inference process in an artificial neural network
Authors: Jang Jingon , Jang Seonghoon , Choi Sanghyeon , Wang Gunuk
Published: January 2021

Generally, the decision rule for classifying unstructured data in an artificial neural network system depends on the sequence results of an activation function determined by vector–matrix multiplication between the input bias signal and the analog synaptic weight quantity of each node in a matrix array. Although a sequence-based decision rule can efficiently extract a common feature in a large data set in a short time, it can occasionally fail to classify similar species because it does not intrinsically consider other quantitative configurations of the activation function that affect the synaptic weight update. In this work, we implemented a simple run-off election-based decision rule via an additional filter evaluation to mitigate the confusion from proximity of output activation functions, enabling the improved training and inference performance of artificial neural network system. Using the filter evaluation selected via the difference among common features of classified images, the recognition accuracy achieved for three types of shoe image data sets reached ~ 82.03%, outperforming the maximum accuracy of ~ 79.23% obtained via the sequence-based decision rule in a fully connected single layer network. This training algorithm with an independent filter can precisely supply the output class in the decision step of the fully connected network.
An ultra-thin double-functional metasurface patch antenna for UHF RFID applications
Authors: Koohestani Mohsen , Ghaneizadeh Alireza
Published: January 2021

An ultra-thin double-functional metasurface patch antenna (MPA) was proposed, where it can operate not only in the antenna mode but also can simultaneously act as perfect absorber for normal incident waves, suitable for RFID applications in the 868 MHz band. The MPA structure consists of a typical coaxially-fed patch antenna merged, for the first time, with a metasurface absorber acting as artificial ground. A methodology for the unit-cell design of the metasurface is proposed followed by an equivalent circuit model analysis, which makes it possible to transform a low-loss ($$tan\delta =0.0015$$

t
a
n
δ
=
0.0015

) unit-cell with highly-reflective characteristics to a perfect absorber for normal incident waves. It is based on modifying the critical external coupling by properly introducing slits on the unit-cell, allowing to design an ultra-thin ($$\lambda _0/225$$

λ
0

/
225

at 868 MHz) and a very compact structure in comparison to previously developed designs. For validation purposes, the MPA was fabricated and its performances in both functional modes were characterized numerically and experimentally. It is demonstrated that merging the absorber with the patch not only allows obtaining a well-matched ($$|S_{11}|<-30$$

|

S
11

|
<
-
30

 dB) antenna with an enhanced gain (by 175.6% compared to a typical patch) at the desired frequency but also leads to an overall thickness of only 2.5 mm ($$\lambda _0/138.1$$

λ
0

/
138.1

at 868 MHz). With an absorber size limited to the MPA dimensions, a reasonable 1.3 dB reduction in powers reflected by the MPA was achieved compared to a similar size metallic sheet. Whilst having the lowest profile among the so far reported RFID readers, the proposed MPA can be conveniently fitted for example within the required volume of smart shelf RFID readers or used in portable RFID readers while being capable of mitigating multipath reflection issues and incorrect reading of RFID.
Melatonin administration provokes the activity of dendritic reticular cells in the seminal vesicle of Soay ram during the non-breeding season
Authors: Abd-Elhafeez Hanan H. , Hassan A. H. S. , Hussein Manal T.
Published: January 2021

Dendritic cells (DCs) are innate immune cells which engulf, process and present antigens to the naïve T-lymphocyte cells. However, little is known about the effect of melatonin on the DCs. The present study aimed to investigate the morphology and distribution of the DCs by transmission electron microscopy and Immunohistochemistry after melatonin administration. A total of 8 out of 15 adult ram was randomly selected to receive the melatonin implant and the remaining 7 animals received melatonin free implants. DCs showed positive immunoreactivity for CD117, S-100 protein and CD34. There is an obvious increase in the number of the positive immunoreactive cells to CD3, estrogen receptor alpha and progesterone in the treated groups. The expression of CD56 and MHCII in the DCs was abundant in the treated groups. The ultrastructure study revealed that melatonin exerts a stimulatory effect on the DCs which was associated with increment in the secretory activity of DCs. The secretory activity demarcated by an obvious increase in the number of mitochondria, cisternae of rER and a well-developed Golgi apparatus. The endosomal- lysosomal system was more developed in the treated groups. A rod-shaped Birbeck granule was demonstrated in the cytoplasm of the melatonin treated group. DCs were observed in a close contact to telocytes, T-Lymphocytes, nerve fibers and blood vessels. Taken together, melatonin administration elicits a stimulatory action on the DCs and macrophages through increasing the size, the number and the endosomal compartments which may correlate to increased immunity.
MicroRNA expression profiling after recurrent febrile seizures in rat and emerging role of miR-148a-3p/SYNJ1 axis
Authors: Xu Jian , Sun Mingqiang , Li Xiaodong , Huang Lei , Gao Zhenzhong , Gao Jian , Xie Anmu
Published: January 2021

Febrile seizures (FSs) are common neurological disorders in both infants and children, although the precise underlying mechanism remains to be explored, especially in the expression pattern and function of microRNAs (miRNAs). In this report, we aimed to screen new potential miRNAs and examine the role of miR-148a-3p in hippocampal neurons in FS rats via Synaptojanin-1 (SYNJ1). Thirty rats were randomly divided into the normal and FS model groups, which were investigated by miRNA array. This process identified 31 differentially expressed (20 upregulated and 11 downregulated) miRNAs and potential miRNA target genes. In addition, hippocampal neurons were assigned into five groups for different transfections. Apoptosis was detected by TUNEL and flow cytometry. SYNJ1 was identified as a target gene of miR-148-3p. In vitro experiments revealed that inhibition of miR-148a-3p decreased neuronal cell apoptosis. Moreover, overexpression of miR-148a-3p resulted in activation of PI3K/Akt signaling pathway and the apoptosis of hippocampal neurons. MiR-148a-3p inhibitor could reverse the above events. Taken together, our data demonstrated that the hippocampal miRNA expression profiles of a rat model of FS provide a large database of candidate miRNAs and neuron-related target genes. Furthermore, miR-148a-3p acted as a apoptosis enhcaner via the activation of the SYNJ1/PI3K/Akt signaling pathway, highlighting a potential therapeutic target in the treatment of infants with hyperthermia-induced brain injury.
Dogs’ insensitivity to scaffolding behaviour in an A-not-B task provides support for the theory of natural pedagogy
Authors: Neilands Patrick , Kingsley-Smith Olivia , Taylor Alex H.
Published: January 2021

Executive function plays a critical role in regulating behaviour. Behaviour which directs attention towards the correct solution leads to increased executive function performance in children, but it is unknown how other animals respond to such scaffolding behaviour. Dogs were presented with an A-not-B detour task. After learning to go through gap A to obtain the reward, the barrier was reversed, and the dogs had to inhibit their learned response and enter through gap B on the opposite side. Failure to do so is known as the perseveration error. In test trials, dogs taking part in one of two scaffolding conditions, a pointing condition, where the experimenter pointed to the new gap, and a demonstration condition, where the experimenter demonstrated the new route, were no less likely to commit the perseveration error than dogs in a control condition with no scaffolding behaviour. Dogs’ lack of responsiveness to scaffolding behaviour provides little support for suggestions that simple social learning mechanisms explains scaffolding behaviour in humans. Instead, our results suggest that the theory of natural pedagogy extends to the development of executive function in humans. This suggests that human children’s predisposition to interpret ostensive-communicative cues as informative may be an innate, species-specific adaptation.
Fine-tuning mitochondrial activity in Yarrowia lipolytica for citrate overproduction
Authors: da Veiga Moreira Jorgelindo , Jolicoeur Mario , Schwartz Laurent , Peres Sabine
Published: January 2021

Yarrowia lipolytica is a non-conventional yeast with promising industrial potentials for lipids and citrate production. It is also widely used for studying mitochondrial respiration due to a respiratory chain like those of mammalian cells. In this study we used a genome-scale model (GEM) of Y. lipolytica metabolism and performed a dynamic Flux Balance Analysis (dFBA) algorithm to analyze and identify metabolic levers associated with citrate optimization. Analysis of fluxes at stationary growth phase showed that carbon flux derived from glucose is rewired to citric acid production and lipid accumulation, whereas the oxidative phosphorylation (OxPhos) shifted to the alternative respiration mode through alternative oxidase (AOX) protein. Simulations of optimized citrate secretion flux resulted in a pronounced lipid oxidation along with reactive oxygen species (ROS) generation and AOX flux inhibition. Then, we experimentally challenged AOX inhibition by adding n-Propyl Gallate (nPG), a specific AOX inhibitor, on Y. lipolytica batch cultures at stationary phase. Our results showed a twofold overproduction of citrate (20.5 g/L) when nPG is added compared to 10.9 g/L under control condition (no nPG addition). These results suggest that ROS management, especially through AOX activity, has a pivotal role on citrate/lipid flux balance in Y. lipolytica. All taken together, we thus provide for the first time, a key for the understanding of a predominant metabolic mechanism favoring citrate overproduction in Y. lipolytica at the expense of lipids accumulation.
An encryption–decryption framework to validating single-particle imaging
Authors: Shen Zhou , Teo Colin Zhi Wei , Ayyer Kartik , Loh N. Duane
Published: January 2021

We propose an encryption–decryption framework for validating diffraction intensity volumes reconstructed using single-particle imaging (SPI) with X-ray free-electron lasers (XFELs) when the ground truth volume is absent. This conceptual framework exploits each reconstructed volumes’ ability to decipher latent variables (e.g. orientations) of unseen sentinel diffraction patterns. Using this framework, we quantify novel measures of orientation disconcurrence, inconsistency, and disagreement between the decryptions by two independently reconstructed volumes. We also study how these measures can be used to define data sufficiency and its relation to spatial resolution, and the practical consequences of focusing XFEL pulses to smaller foci. This conceptual framework overcomes critical ambiguities in using Fourier Shell Correlation (FSC) as a validation measure for SPI. Finally, we show how this encryption-decryption framework naturally leads to an information-theoretic reformulation of the resolving power of XFEL-SPI, which we hope will lead to principled frameworks for experiment and instrument design.
Retinal capillary rarefaction is associated with arterial and kidney damage in hypertension
Authors: Frost Shaun , Nolde Janis Marc , Chan Justine , Joyson Anu , Gregory Cynthia , Carnagarin Revathy , Herat Lakshini Y. , Matthews Vance B. , Robinson Liam , Vignarajan Janardhan , Prentice David , Kanagasingam Yogesan , Schlaich Markus P.
Published: January 2021

Microvascular disease and rarefaction are key pathological hallmarks of hypertension. The retina uniquely allows direct, non-invasive investigation of the microvasculature. Recently developed optical coherence tomography angiography now allows investigation of the fine retinal capillaries, which may provide a superior marker of overall vascular damage. This was a prospective cross-sectional study to collect retinal capillary density data on 300 normal eyes from 150 hypertensive adults, and to investigate possible associations with other organ damage markers. The average age of participants was 54 years and there was a greater proportion of males (85; 57%) than females. Multivariate, confounder adjusted linear regression showed that retinal capillary rarefaction in the parafovea was associated with increased pulse wave velocity (β = − 0.4,P = 0.04), log-albumin/creatinine ratio (β = − 0.71,P = 0.003), and with reduced estimated glomerular filtration rate (β = 0.04,P = 0.02). Comparable significant associations were also found for whole-image vascular-density, for foveal vascular-density significant associations were found with pulse wave velocity and estimated glomerular filtration rate only. Our results indicate that retinal capillary rarefaction is associated with arterial stiffness and impaired kidney function. Retinal capillary rarefaction may represent a useful and simple test to assess the integrated burden of hypertension on the microvasculature irrespective of current blood pressure levels.
Omega-7 oil increases telomerase activity and accelerates healing of grafted burn and donor site wounds
Authors: Niimi Yosuke , Pérez-Bello Dannelys , Ihara Koji , Fukuda Satoshi , Jacob Sam , Andersen Clark R. , Baljinnyam Tuvshintugs , Kim Jisoo , Alharbi Suzan , Prough Donald S. , Enkhbaatar Perenlei
Published: January 2021

This study investigated the efficacy of Omega-7 isolated from the sea buckthorn oil (Polyvit Co., Ltd, Gangar Holding, Ulaanbaatar, Mongolia) in ovine burn wound healing models. In vitro, proliferation (colony-forming rate) and migration (scratch) assays using cultured primary ovine keratinocytes were performed with or without 0.025% and 0.08% Omega-7, respectively. The colony-forming rate of keratinocytes in the Omega-7 group at 72 and 96 h were significantly higher than in the control (P < 0.05). The percentage of closure in scratch assay in the Omega-7 group was significantly higher than in the control at 17 h (P < 0.05). In vivo, efficacy of 4% Omega-7 isolated from buckthorn oil was assessed at 7 and 14 days in grafted ovine burn and donor site wounds. Telomerase activity, keratinocyte growth factor, and wound nitrotyrosine levels were measured at day 14. Grafted sites: Un-epithelialized raw surface area was significantly lower and blood flow was significantly higher in the Omega-7-treated sites than in control sites at 7 and 14 days (P < 0.05). Telomerase activity and levels of keratinocyte growth factors were significantly higher in the Omega-7-treated sites after 14 days compared to those of control (P < 0.05). The wound 3-nitrotyrosine levels were significantly reduced by Omega-7. Donor sites: the complete epithelialization time was significantly shorter and blood flow at day 7 was significantly higher in the Omega-7-treated sites compared to control sites (P < 0.05). In summary, topical application of Omega-7 accelerates healing of both grafted burn and donor site wounds. Omega-7 should be considered as a cost-efficient and effective supplement therapy for burn wound healing.
Discrimination of natural acoustic variation in vocal signals
Authors: Fishbein Adam R. , Prior Nora H. , Brown Jane A. , Ball Gregory F. , Dooling Robert J.
Published: January 2021

Studies of acoustic communication often focus on the categories and units of vocalizations, but subtle variation also occurs in how these signals are uttered. In human speech, it is not only phonemes and words that carry information but also the timbre, intonation, and stress of how speech sounds are delivered (often referred to as “paralinguistic content”). In non-human animals, variation across utterances of vocal signals also carries behaviorally relevant information across taxa. However, the discriminability of these cues has been rarely tested in a psychophysical paradigm. Here, we focus on acoustic communication in the zebra finch (Taeniopygia guttata), a songbird species in which the male produces a single stereotyped motif repeatedly in song bouts. These motif renditions, like the song repetitions of many birds, sound very similar to the casual human listener. In this study, we show that zebra finches can easily discriminate between the renditions, even at the level of single song syllables, much as humans can discriminate renditions of speech sounds. These results support the notion that sensitivity to fine acoustic details may be a primary channel of information in zebra finch song, as well as a shared, foundational property of vocal communication systems across species.
Assessment of the pulmonary adaptive immune response to Cladosporium cladosporioides infection using an experimental mouse model
Authors: Ma Xiaoping , Hu Jing , Yu Yan , Wang Chengdong , Gu Yu , Cao Sanjie , Huang Xiaobo , Wen Yiping , Zhao Qin , Wu Rui , Zuo Zhicai , Deng Junliang , Ren Zhihua , Yu Shumin , Shen Liuhong , Zhong Zhijun , Peng Guangneng
Published: January 2021

Cladosporium cladosporioides causes asthma and superficial and deep infections, mostly in immunodeficient individuals and animals. This study aimed to investigate whether C. cladosporioides spores can enter the lungs through pulmonary circulation and influence pulmonary immune response. We intravenously injected mice with C. cladosporioides spore suspension and conducted several assays on the lungs. Pulmonary hemorrhage symptoms and congestion were most severe on days 1, 2, and 3 post-inoculation (PI). Extensive inflammatory cell infiltration occurred throughout the period of infection. More spores and hyphae colonizing the lungs were detected on days 1, 2, and 3 PI, and fewer spores and hyphae were observed within 21 d of infection. Numerous macrophages, dendritic cells, and neutrophils were observed on day 5 PI, along with upregulation of CD54, an intercellular adhesion molecule. Th1 and Th2 cells increased after infection; specifically, Th2 cells increased considerably on day 5 PI. These results suggest that days 2 and 5 PI represent the inflammatory peak in the lungs and that the Th2 and Th1 signaling pathways are potentially involved in pulmonary immune responses. In conclusion, the further adaptive immune responses played important roles in establishing effective pulmonary immunity against C. cladosporioides systemic infections based on innate immune responses.
Wrist-wearable bioelectrical impedance analyzer with miniature electrodes for daily obesity management
Authors: Jung Myoung Hoon , Namkoong Kak , Lee Yeolho , Koh Young Jun , Eom Kunsun , Jang Hyeongseok , Jung Wonjong , Bae Jungmok , Park Jongae
Published: January 2021

Bioelectrical impedance analysis (BIA) is used to analyze human body composition by applying a small alternating current through the body and measuring the impedance. The smaller the electrode of a BIA device, the larger the impedance measurement error due to the contact resistance between the electrode and human skin. Therefore, most commercial BIA devices utilize electrodes that are large enough (i.e., 4 × 1400 mm2) to counteract the contact resistance effect. We propose a novel method of compensating for contact resistance by performing 4-point and 2-point measurements alternately such that body impedance can be accurately estimated even with considerably smaller electrodes (outer electrodes: 68 mm2; inner electrodes: 128 mm2). Additionally, we report the use of a wrist-wearable BIA device with single-finger contact measurement and clinical test results from 203 participants at Seoul St. Mary’s Hospital. The correlation coefficient and standard error of estimate of percentage body fat were 0.899 and 3.76%, respectively, in comparison with dual-energy X-ray absorptiometry. This result exceeds the performance level of the commercial upper-body portable body fat analyzer (Omron HBF-306). With a measurement time of 7 s, this sensor technology is expected to provide a new possibility of a wearable bioelectrical impedance analyzer, toward obesity management.
Separate and combined Hanseniaspora uvarum and Metschnikowia pulcherrima metabolic volatiles are attractive to Drosophila suzukii in the laboratory and field
Authors: Jones R. , Fountain M. T. , Günther C. S. , Eady P. E. , Goddard M. R.
Published: January 2021

Drosophila suzukii flies cause economic losses to fruit crops globally. Previous work shows various Drosophila species are attracted to volatile metabolites produced by individual fruit associated yeast isolates, but fruits naturally harbour a rich diversity of yeast species. Here, we report the relative attractiveness of D. suzukii to yeasts presented individually or in combinations using laboratory preference tests and field trapping data. Laboratory trials revealed four of 12 single yeast isolates were attractive to D. suzukii, of which Metschnikowia pulcherrima and Hanseniaspora uvarum were also attractive in field trials. Four out of 10 yeast combinations involving Candida zemplinina, Pichia pijperi, M. pulcherrima and H. uvarum were attractive in the laboratory. Whilst a combination of M. pulcherrima + H. uvarum trapped the greatest number of D. suzukii in the field, the efficacy of the M. pulcherrima + H. uvarum combination to trap D. suzukii was not significantly greater than traps primed with volatiles from only H. uvarum. While volatiles from isolates of M. pulcherrima and H. uvarum show promise as baits for D. suzukii, further research is needed to ascertain how and why flies are attracted to certain baits to optimise control efficacy.
Measurement of muscle blood flow and O2 uptake via near-infrared spectroscopy using a novel occlusion protocol
Authors: Dennis Joshua J. , Wiggins Chad C. , Smith Joshua R. , Isautier Jennifer M. J. , Johnson Bruce D. , Joyner Michael J. , Cross Troy J.
Published: January 2021

We describe here a novel protocol that sequentially combines venous followed by arterial occlusions to determine muscle blood flow and O2 uptake from a single measurement point using near-infrared spectroscopy (NIRS) during handgrip exercise. NIRS data were obtained from the flexor digitorum superficialis (FDS) muscle on the dominant arm of 15 young, healthy adults (3 women; 26 ± 7 years; 78.6 ± 9.1 kg). Participants completed a series of 15-s static handgrip contractions at 20, 40 and 60% of maximal voluntary contraction (MVC) immediately followed by either a: (i) venous occlusion (VO); (ii); arterial occlusion (AO); or venous then arterial occlusion (COMBO). Each condition was repeated 3 times for each exercise-intensity. The concordance correlation coefficient (CCC) and robust linear mixed effects modeling were used to determine measurement agreement between vascular occlusion conditions. FDS muscle blood flow ($${\dot{\text{Q}}}_{{{\text{FDS}}}}$$

Q
˙

FDS

) and conductance ($${\text{C}}_{{{\text{FDS}}}}$$

C
FDS

) demonstrated strong absolute agreement between VO and COMBO trials from rest up to 60%MVC, as evidenced by high values for CCC (> 0.82) and a linear relationship between conditions that closely approximated the line-of-identity (perfect agreement). Conversely, although FDS muscle O2 uptake ($${{\dot {\text{V}}}}{{\text{O}}_{2{\text{FDS}}}}$$

V
˙

O

2
FDS

) displayed “substantial” to “near perfect” agreement between methods across exercise intensities (i.e., CCC > 0.80), there was a tendency for COMBO trials to underestimate $${{\dot {\text{V}}}}{{\text{O}}_{2{\text{FDS}}}}$$

V
˙

O

2
FDS

by up to 7%. These findings indicate that the COMBO method provides valid estimates of $${\dot {\text{Q}}}_{{\text{FDS}}}$$

Q
˙

FDS

and, to a slightly lesser extent, $${{\dot {\text{V}}}}{{\text{O}}_{2{\text{FDS}}}}$$

V
˙

O

2
FDS

at rest and during static handgrip exercise up to 60%MVC. Practical implications and suggested improvements of the method are discussed.
Computational analyses decipher the primordial folding coding the 3D structure of the beetle horn
Authors: Matsuda Keisuke , Gotoh Hiroki , Adachi Haruhiko , Inoue Yasuhiro , Kondo Shigeru
Published: January 2021

The beetle horn primordium is a complex and compactly folded epithelial sheet located beneath the larval cuticle. Only by unfolding the primordium can the complete 3D shape of the horn appear, suggesting that the morphology of beetle horns is encoded in the primordial folding pattern. To decipher the folding pattern, we developed a method to manipulate the primordial local folding on a computer and clarified the contribution of the folding of each primordium region to transformation. We found that the three major morphological changes (branching of distal tips, proximodistal elongation, and angular change) were caused by the folding of different regions, and that the folding mechanism also differs according to the region. The computational methods we used are applicable to the morphological study of other exoskeletal animals.