bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated balancing method for series‐parallel battery packs based on LC energy storage
Authors: Guo Xiangwei , Liu Zhen , Xu Xiaozhuo , Geng Jiahao , Kang Longyun
Published: March 2021

Inconsistencies are inevitable in the practical application of battery packs of new energy vehicles, which will reduce the energy utilisation rate and service life and even endanger the safety of the battery system. To reduce the inconsistency of battery packs, this study innovatively proposes an integrated active balancing method for series‐parallel battery packs based on LC energy storage. Only one inductor and one capacitor are used to store energy to achieve the balance of each cell in a series‐parallel battery pack. This design has the characteristics of simple structure, small volume, fast balancing speed and easy expansion. By building an experimental platform, the effectiveness of this novel integrated balancing method is verified.
Extraction of optimal fatigue‐driving steering indicators considering individual differences
Authors: Sun Yifan , Wu Chaozhong , Zhang Hui , Zhou Wei , Li Xin , Zhang Qi
Published: March 2021

Extracting effective steering indicators is critical for fatigue‐identification based on steering behaviour. However, considering individual differences, the best calculation parameters of the individual driver's steering indicators are different. The indicator's performance decreases by using unified parameters rather than the individual driver's best parameters. The authors propose a model extracting individual driver's optimal fatigue steering indicators calculated by the individual driver's best parameters. Individual driver's naturalistic driving data are analysed by the model. First, indicators in sober and fatigue state are examined by the Wilcoxon test, and |Z| represents the indicator's fatigue‐identification performance. And the function reflecting correspondences between calculation parameters and indicator's fatigue‐identification performance is constructed. Then the function is optimized using particle swarm optimization to obtain individual driver's best calculation parameters maximizing |Z|. Finally, effective indicators calculated by the individual driver's best parameters constitute the individual driver's optimal fatigue indicator set. Indicators calculated by the individual driver's best parameters and unified parameters are used to establish the individual fatigue‐identification model. The average identification accuracy of models using individual driver's best parameters and unified parameters is 87.4% and 79.1%, which indicates using individual driver's optimal fatigue indicators can improve identification accuracy. This study can provide references for individualized fatigue‐driving identification
Non‐invasive sound‐based classifier of bearing faults in electric induction motors
Authors: Santos Herman , Scalassara Paulo , Endo Wagner , Goedtel Alessandro , Guedes Jacqueline , Gentil Murillo
Published: March 2021

Induction motors play a major role in the industry nowadays due to their simple construction, uncomplicated maintenance, and cost efficiency. As the motor operates for repeated hours, some faults may occur and, depending on the process sensitivity, can cause significant losses to the industrial production. In this context, an alternative method is proposed to detect and classify bearing faults using acoustic emission signals generated by the machines and simple features obtained from them. A pair of condenser microphones was used to acquire these signals and audio feature extraction is performed to obtain time and frequency patterns to characterize healthy and faulty machines. The major differences of the acoustic signals regarding the fault frequency signatures are discussed by analyzing specific peaks observed in their spectra. Several coupled load values and levels of power supply voltage unbalance were considered in the experimental tests, which emulate common situations encountered in industrial environments, obtaining accuracy rates over 97% of success. Finally, a comparison is presented of machine learning techniques for bearing faults classification under different load values and voltage unbalance levels.
Building cultural capital in drought adaptation: lessons from discourse analysis
Authors: Paxton Gillian
Published: March 2021

As governments and primary industries work to build the climate resilience of Australian agriculture, individual producers are often called upon to implement strategies to become more adaptive in the face of drought. These strategies include infrastructural changes to agricultural businesses, changes to practices, and the adoption of new skills and knowledge. The transition towards greater drought adaptiveness will also demand broader cultural shifts in the way that drought is defined and approached as an issue facing primary producers. This paper presents the results of a discourse analysis conducted as part of social research exploring the cultural barriers to drought preparedness within the Queensland Government’s Drought and Climate Adaptation Program (DCAP). Focusing on media and government accounts, the analysis found two different ways of framing drought and its management in Queensland agriculture. The first, which is dominant in media accounts, emphasises the disruptive power of drought, presenting it as a profound difficulty for producers that is managed using endurance, hope and ingenuity. This frame adopts highly evocative discursive strategies oriented towards mobilising community sentiment and support for producers. The second, which is less prominent overall, downplays drought’s disruptive power and counters the emotionality of the adversity discourse by presenting drought as a neutral business risk that can be managed using rational planning skills and scientific knowledge. In discussing these two frames, this paper suggests strategies whereby drought adaptation frames might be made more powerful using more meaningful and emotive narratives that showcase it as a vital practice for ensuring agricultural livelihoods and rural futures in a changing climate.
Stature is negatively associated with increased arterial stiffness after high‐intensity bicep curls training in young Japanese men
Authors: Tagawa Kaname , Choi Youngju , Ra Song‐Gyu , Yoshikawa Toru , Kumagai Hiroshi , Maeda Seiji
Published: March 2021

Reports have indicated that high‐intensity resistance training (RT) increases or does not change arterial stiffness. Meanwhile, higher stature has been suggested to have a protective effect on cardiovascular disease and arterial stiffness. Stature could explain the disagreement in the reported effects of RT on arterial stiffness. This study was aimed at investigating whether stature is related to RT‐induced change in arterial stiffness. Thirty‐six young Japanese men were assigned to the control (n = 15) and training groups (n = 21). RT programme consisted of supervised bicep curls 3 days per week for 4 weeks (5 sets of 10 repetitions at 75% of 1‐repetition maximum). Arterial compliance (AC) and β‐stiffness index (via combination of ultrasound and carotid pressure waveforms) were measured in all participants. To verify the effect of stature on RT‐induced change in arterial stiffness, the training group was divided into tertiles of stature: lower, middle, and higher stature groups (each group, n = 7). RT significantly decreased AC and increased β‐stiffness index in only the lower stature group (both, P < 0.05). Moreover, stature was positively associated with decreased AC and negatively associated with increased β‐stiffness index, even after adjusting for confounders including changes in relative strength, pulse pressure, and arterial distension (P < 0.05). The present results suggest that short stature contributes to the increase in arterial stiffness induced by RT in young Japanese men. The present findings suggest that stature should be taken into consideration when designing/engaging in RT programme, due to potential implications for cardiovascular health.

Highlights

Participants were divided into 3 groups according to tertiles of statures, and arterial stiffness of lower stature group (range of stature: 161.0–169.8 cm) increased after resistance training in young Japanese men, but not middle and higher stature group.

Stature was negatively associated with the changed arterial stiffness by resistance training.

This study suggests that short stature contributes to the elevation in arterial stiffness elicited by resistance training.
Hepatic Histopathology Among Excessive Drinkers Without Advanced Liver Disease
Authors: Chang Binxia , Huang Ang , Saxena Romil , Sun Yin , Liu Shuhong , Zhou Guangde , Li Baosen , Teng Guangju , Zhao Jun , Zhang Wei , Jiang Yanchao , Han Sen , Yang Zhihong , Zhao Jingmin , Zou Zhengsheng , Liangpunsakul Suthat
Published: March 2021

Aims

Alcohol-associated liver disease represents a spectrum of histopathological changes from steatosis to advanced fibrosis and cirrhosis. The major goals of this retrospective study were to characterize the histologic features in patients with excessive alcohol use who presented with an abnormal hepatic panel and/or abnormal radiographic imaging and did not meet the clinical diagnosis of alcoholic hepatitis or cirrhosis.

Methods

We performed a retrospective study to describe hepatic histology of 62 and 83 excessive drinkers with normal and abnormal serum aspartate transaminase, respectively. The types of inflammatory cells in the liver were characterized by immunohistochemistry for CD4, CD8, CD20, CD68 and myeloperoxidase.

Results

Among 62 patients with aspartate aminotransferase (AST) ≤ 50 U/L, 37% had histological evidence of steatosis. Of these, we found evidence of hepatocyte ballooning (21%), lobular inflammation (50%), portal inflammation (52%) and fibrosis (14%). For those with AST > 50 U/L, the presence of hepatic steatosis, lobular inflammation and portal inflammation was observed in 29, 60 and 69% of patients, respectively. Fibrosis was found in 33%, four with bridging fibrosis, and one with cirrhosis. We observed the aggregation of CD68+ macrophages, rather than normally distributed with minimal neutrophilic infiltration. Lobular and portal lymphocytic infiltrations are primarily CD8+ T cells.

Conclusion

Abnormal hepatic histopathology occurs in excessive drinkers with normal transaminase activity. Future studies to determine the diagnostic modalities to detect such abnormalities and to better understand its clinical implications and long-term outcome are needed.
Static cold storage compared with normothermic machine perfusion of the liver and effect on ischaemic-type biliary lesions after transplantation: a propensity score-matched study
Authors: Fodor M , Cardini B , Peter W , Weissenbacher A , Oberhuber R , Hautz T , Otarashvili G , Margreiter C , Maglione M , Resch T , Krendl F , Meszaros A T , Bogensperger C , Gasteiger S , Messner F , Henninger B , Zoller H , Tilg H , Öfner D , Schneeberger S
Published: March 2021

Background

Given the susceptibility of organs to ischaemic injury, alternative preservation methods to static cold storage (SCS), such as normothermic machine perfusion (NMP) are emerging. The aim of this study was to perform a comparison between NMP and SCS in liver transplantation with particular attention to bile duct lesions.

Methods

The outcomes of 59 consecutive NMP-preserved donor livers were compared in a 1 : 1 propensity score-matched fashion to SCS control livers. Postoperative complications, patient survival, graft survival and bile duct lesions were analysed.

Results

While patients were matched for cold ischaemia time, the total preservation time was significantly longer in the NMP group (21 h versus 7 h, P < 0.001). Patient and graft survival rates at 1 year were 81 versus 82 per cent (P = 0.347) and 81 versus 79 per cent (P = 0.784) in the NMP and SCS groups, respectively. The postoperative complication rate was comparable (P = 0.086); 37 per cent NMP versus 34 per cent SCS patients had a Clavien-Dindo grade IIIb or above complication. There was no difference in early (30 days or less) (NMP 22 versus SCS 19 per cent, P = 0.647) and late (more than 30 days) (NMP 27 versus SCS 36 per cent, P = 0.321) biliary complications. However, NMP-preserved livers developed significantly fewer ischaemic-type bile duct lesions (NMP 3 versus SCS 14 per cent, P = 0.047).

Conclusion

The use of NMP allowed for a significantly prolonged organ preservation with a lower rate of observed ischaemic-type bile duct lesions.
Transnational Islamic Finance Disputes: Towards a Convergence with English Contract Law and International Arbitration
Authors: Bantekas Ilias
Published: March 2021

While Islamic finance is premised on wholly antithetical rules and notions as opposed to traditional Western finance, the resolution of pertinent disputes has been structured along the lines of standard commercial arbitration. Islam has always favoured arbitration and mediation and in fact promoted these in very much liberal terms. As a result, there has never been a need to adapt a sui generis Islamic dimension to Islamic finance, because clearly Western and Islamic notions of arbitration largely coincide. In recent years there have been some attempts to limit Islamic finance arbitration within a narrow understanding of Islamic ethics, despite the fact that it has become transnational in character and Islamic ethics are in any event inbuilt in the architecture of Islamic finance instruments, which arbitrators can only avoid at their peril. It is no wonder that Muslim end users generally prefer to resolve disputes arising from Islamic finance transactions in conventional arbitral institutions, while at the same time choosing English law to govern their agreement, typically concurrently with Islamic law or other laws. As a result, Islamic finance has equally attracted non-Muslim end users. The English High Court has not only developed a particular expertise in Islamic finance law but has, in addition, demonstrated how Islamic and secular law are generally compatible and complementary (with some notable exceptions) in construing transnational Islamic finance. At the same time, institutions and rules in the Muslim world that depart from the global arbitration paradigm are fast falling into desuetude. In light of these findings, it is argued that a sui generis Islamic finance arbitration model is not only disfavoured by end users as being out of touch with business reality but is inconsistent with the fundamental tenets of the Islamic law of arbitration.
The radio galaxy population in the simba simulations
Authors: Thomas Nicole , Davé Romeel , Jarvis Matt J , Anglés-Alcázar Daniel
Published: March 2021

We examine the 1.4 GHz radio luminosities of galaxies arising from star formation and active galactic nuclei (AGNs) within the state-of-the-art cosmological hydrodynamic simulation Simba. Simba grows black holes via gravitational torque limited accretion from cold gas and Bondi accretion from hot gas, and employs AGN feedback including jets at low Eddington ratios. We define a population of radio loud AGNs (RLAGNs) based on the presence of ongoing jet feedback. Within RLAGN, we define high and low excitation radio galaxies (HERGs and LERGs) based on their dominant mode of black hole accretion: torque limited accretion representing feeding from a cold disc, or Bondi representing advection-dominated accretion from a hot medium. Simba predicts good agreement with the observed radio luminosity function (RLF) and its evolution, overall as well as separately for HERGs and LERGs. Quiescent galaxies with AGN-dominated radio flux dominate the RLF at $\gtrsim 10^{22-23}$ W Hz−1, while star formation dominates at lower radio powers. Overall, RLAGNs have higher black hole accretion rates and lower star formation rates than non-RLAGN at a given stellar mass or velocity dispersion, but have similar black hole masses. Simba predicts an LERG number density of 8.53 Mpc−3, ∼10× higher than for HERGs, broadly as observed. While LERGs dominate among most massive galaxies with the largest black holes and HERGs dominate at high specific star formation rates, they otherwise largely populate similar-sized dark matter haloes and have similar host galaxy properties. Simba thus predicts that deeper radio surveys will reveal an increasing overlap between the host galaxy demographics of HERGs and LERGs.
Pathological role of activated mTOR in CXCR3+ memory B cells of rheumatoid arthritis
Authors: Iwata Shigeru , Zhang Mingzeng , Hajime Maiko , Ohkubo Naoaki , Sonomoto Koshiro , Torimoto Keiichi , Kitanaga Yukihiro , Trimova Gulzhan , Todoroki Yasuyuki , Miyata Hiroko , Ueno Masanobu , Nagayasu Atsushi , Kanda Ryuichiro , Nakano Kazuhisa , Nakayamada Shingo , Sakata Kei , Tanaka Yoshiya
Published: March 2021

Objectives

B cells play an important pathological role in RA. In this study, we investigated the role of metabolic regulator mTOR in B cells and its relevance to the pathology of RA.

Methods

Peripheral blood mononuclear cells were isolated from 31 normal subjects and 86 RA patients and the gated B cells were assessed for mTOR phosphorylation and chemokine receptor expression. In vitro studies on peripheral blood B cells isolated from the control and RA patients investigated the molecular mechanisms.

Results

Higher concentrations of CXCL10 (CXCR3 ligands) and lower percentages of CXCR3+ memory B cells were present in the peripheral blood of RA patients relative to the control. RA patients with high CXCL10 concentrations had smaller percentage of CXCR3+ memory B cells and high disease activity. One-year treatment with TNF inhibitors increased the percentage of CXCR3+ memory B cells and reduced serum CXCL10 concentrations. mTOR phosphorylation in B cells was further enhanced in RA patients, compared with the control, and was selectively enhanced in CXCR3+ memory B cells. mTOR phosphorylation in CXCR3+ memory B cells correlated with disease activity. In vitro, mTOR phosphorylation in B cells enhanced IL-6 production and increased RANKL expression.

Conclusion

mTOR activation in CXCR3+ memory B cells of RA patients is associated with disease activity, mediated through IL-6 production and RANKL expression. The obtained results also suggest that TNF inhibitors mediate an impact on the association between CXCL10 and mTOR activated CXCR3+ memory B cells.
Bilateral Acute Angle Closure in a Pediatric Patient Taking Lisdexamfetamine Dimesylate (Vyvanse)
Authors: Davanian Arash M. , Fitzpatrick John C. , Tran Duy P. , Korducki John P. , Groth Sylvia L.
Published: March 2021

Attention-deficit/hyperactivity disorder is commonly treated with amphetamines as first line therapy. Rare case reports have shown amphetamines are associated with open angle glaucoma. We report a rare case of a 14-year-old male who presented with bilateral acute angle closure presumed to be related to his use of lisdexamfetamine dimesylate (Vyvanse). The patient’s medication was discontinued which resulted in complete resolution of angle closure.
Increasing Men’s Engagement in HIV Testing and Treatment Programs Through Crowdsourcing: A Mixed-Methods Analysis in Eswatini
Authors: Hlatshwako Takhona , Conserve Donaldson , Day Suzanne , Reynolds Zahra , Weir Sharon , Tucker Joseph D.
Published: March 2021

Background

Sub-Saharan African HIV programs have had limited success in engaging men. Crowdsourcing contests may be a useful method to spur men's engagement in HIV services. We evaluated contributions and social media response to a crowdsourcing contest focused on increasing men's engagement in Eswatini HIV services.

Methods

We conducted a crowdsourcing contest to gain insight from the public on how HIV campaigns can more effectively engage young (20–40 years old) men in HIV services. Eligible submissions included images, songs, videos, and Internet memes. We used standard qualitative methods to examine textual themes from submissions. We examined social media response using Facebook analytics, comparing the number of people reached through crowdsourced HIV messages and the number of people reached through conventional HIV messages.

Results

We received 144 submissions from 83 participants. They represented 55 towns and all 4 regions of Eswatini. The contest page gained 461 followers on Facebook. Emergent themes included appealing to men's roles as protectors by suggesting that they need to take care of their own health to continue safeguarding their families. Crowdsourced messages reached a mean of 88 individuals across 4 posts; conventional messages reached a mean of 75 individuals across 4 posts.

Conclusions

Crowdsourcing contest submissions provided insight on how to encourage men to engage in Eswatini HIV services. Crowdsourcing contests can be effective in collecting messages from men to create more locally relevant communication materials for HIV programs.
The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia
Authors: Skrapits Katalin , Sárvári Miklós , Farkas Imre , Göcz Balázs , Takács Szabolcs , Rumpler Éva , Váczi Viktória , Vastagh Csaba , Rácz Gergely , Matolcsy András , Solymosi Norbert , Póliska Szilárd , Tóth Blanka , Erdélyi Ferenc , Szabó Gábor , Culler Michael D. , Allet Cécile , Cotellessa Ludovica , Prévot Vincent , Giacobini Paolo , Hrabovszky Erik
Published: March 2021

Human reproduction is controlled by ∼2,000 hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Here we report the discovery and characterization of additional 150-200,000 GnRH-synthesizing cells in the human basal ganglia and basal forebrain. Extrahypothalamic GnRH neurons were cholinergic. Though undetectable in adult rodents, the GnRH-GFP transgene was expressed transiently by caudate-putamen cholinergic interneurons in newborn transgenic mice. In slice electrophysiological studies, GnRH inhibited these interneurons via GnRHR1 autoreceptors. Whole-transcriptome analysis of cholinergic interneurons and medium spiny projection neurons laser-microdissected from the human putamen confirmed selective expression ofGNRH1andGNRHR1autoreceptors in cholinergic cells and uncovered the detailed transcriptome profile and molecular connectome of these two cell types. Higher- order non-reproductive functions regulated by GnRH under physiological conditions in the human basal ganglia and basal forebrain require clarification. GnRH/GnRHR1 signaling as a potential therapeutic target in the treatment of neurodegenerative disorders affecting cholinergic neurocircuitries, including Parkinson’s and Alzheimer’s diseases, needs to be explored.
CFAP61 is required for sperm flagellum formation and male fertility in human and mouse
Authors: Liu Siyu , Zhang Jintao , Kherraf Zine Eddine , Sun Shuya , Zhang Xin , Cazin Caroline , Coutton Charles , Zouari Raoudha , Zhao Shuqin , Hu Fan , Mustapha Selima Fourati Ben , Arnoult Christophe , Ray Pierre F , Liu Mingxi
Published: March 2021

Defects in the structure or motility of cilia and flagella may lead to severe diseases such as primary ciliary dyskinesia (PCD), a multisystemic disorder with heterogeneous manifestations affecting primarily respiratory and reproductive functions. We report that CFAP61 is a conserved component of the Calmodulin and radial Spoke associated Complex (CSC) of cilia. We find that a CFAP61 splice variant, c.143+5G>A, causes exon skipping in human, inducing a multiple morphological abnormalities of the flagella (MMAF) phenotype. We generatedCfap61knockout mice that recapitulate the infertility phenotype of the human CFAP61 mutation, but without other symptoms usually observed in PCD. We find that CFAP61 interacts with the CSC, radial spoke stalk and RS head. During early stages ofCfap61−/−spermatid development, the assembly of RS components is impaired. With the progress of spermiogenesis, the axoneme inCfap61−/−cells becomes unstable and scatters, and the distribution of intraflagellar transport proteins is disrupted. This study reveals an organ specific mechanism of axoneme stabilization that is related to male infertility.
Diffusional Kurtosis Imaging in the Diffusion Imaging in Python Project
Authors: Neto Henriques Rafael , Correa Marta , Maralle Maurizio , Huber Elizabeth , Kruper John , Koudoro Serge , Yeatman Jason , Garyfallidis Eleftherios , Rokem Ariel
Published: March 2021

Diffusion-weighted magnetic resonance imaging (dMRI) measurements and models provide information about brain connectivity and are sensitive to the physical properties of tissue microstructure. Diffusional Kurtosis Imaging (DKI) quantifies the degree of non-Gaussian diffusion in biological tissue from dMRI. These estimates are of interest because they were shown to be more sensitive to microstructural alterations in health and diseases than measures based on the total anisotropy of diffusion which are highly confounded by tissue dispersion and fiber crossings. In this work, we implemented DKI in the Diffusion in Python (DIPY) project - a large collaborative open-source project which aims to provide well-tested, well-documented and comprehensive implementation of different dMRI techniques. We demonstrate the functionality of our methods in numerical simulations with known ground truth parameters and in openly available datasets. A particular strength of our DKI implementations is that it pursues several extensions of the model that connect it explicitly with microstructural models and the reconstruction of 3D white matter fiber bundles (tractography). For instance, our implementations include DKI-based microstructural models that allow the estimation of biophysical parameters, such as axonal water fraction. Moreover, we illustrate how DKI provides more general characterization of non-Gaussian diffusion compatible with complex white matter fiber architectures and grey matter, and we include a novel mean kurtosis index that is invariant to the confounding effects due to tissue dispersion. In summary, DKI in DIPY provides a well-tested, well-documented and comprehensive reference mplementation for DKI. It provides a platform for wider use of DKI in research on brain disorders and cognitive neuroscience research. It will ease the translation of DKI advantages into clinical applications.
Evolutionary optimization in classification of early-MCI patients from healthy controls using graph measures of resting-state fMRI
Authors: Zamani Jafar , Sadr Ali , Javadi Amir-Homayoun
Published: March 2021

Abstracts

Identifying individuals with early mild cognitive impairment (EMCI) can be an effective strategy for early diagnosis and delay the progression of Alzheimer’s disease (AD). Many approaches have been devised to discriminate those with EMCI from healthy control (HC) individuals. Selection of the most effective parameters has been one of the challenging aspects of these approaches. In this study we suggest an optimization method based on five evolutionary algorithms that can be used in optimization of neuroimaging data with a large number of parameters. Resting-state functional magnetic resonance imaging (rs-fMRI) measures, which measure functional connectivity, have been shown to be useful in prediction of cognitive decline. Analysis of functional connectivity data using graph measures is a common practice that results in a great number of parameters. Using graph measures we calculated 1155 parameters from the functional connectivity data of HC (n=36) and EMCI (n=34) extracted from the publicly available database of the Alzheimer’s disease neuroimaging initiative database (ADNI). These parameters were fed into the evolutionary algorithms to select a subset of parameters for classification of the data into two categories of EMCI and HC using a two-layer artificial neural network. All algorithms achieved classification accuracy of 94.55%, which is extremely high considering single-modality input and low number of data participants. These results highlight potential application of rs-fMRI and efficiency of such optimization methods in classification of images into HC and EMCI. This is of particular importance considering that MRI images of EMCI individuals cannot be easily identified by experts.
A chemical screen based on an interruption of zebrafish gastrulation identifies the HTR2C inhibitor Pizotifen as a suppressor of EMT-mediated metastasis
Authors: Nakayama Joji , Tan Lora , Goh Boon Cher , Wang Shu , Makinoshima Hideki , Gong Zhiyuan
Published: March 2021

Metastasis is responsible for approximately 90% of cancer-associated mortality but few models exist that allow for rapid and effective screening of anti-metastasis drugs. Current mouse models of metastasis are too expensive and time consuming to use for rapid and high-throughput screening. Therefore, we created a unique screening concept utilizing conserved mechanisms between zebrafish gastrulation and cancer metastasis for identification of potential anti-metastatic drugs. We hypothesized that small chemicals that interrupt zebrafish gastrulation might also suppress metastatic progression of cancer cells and developed a phenotype-based chemical screen to test the hypothesis. The screen used epiboly, the first morphogenetic movement in gastrulation, as a marker and enabled 100 chemicals to be tested in five hours. The screen tested 1280 FDA-approved drugs and identified Pizotifen, an antagonist for serotonin receptor 2C (HTR2C) as an epiboly-interrupting drug. Pharmacologic and genetic inhibition of HTR2C suppressed metastatic progression in a mouse model. Blocking HTR2C with Pizotifen restored epithelial properties to metastatic cells through inhibition of Wnt-signaling. In contrast, HTR2C induced epithelial to mesenchymal transition (EMT) through activation of Wnt-signaling and promoted metastatic dissemination of human cancer cells in a zebrafish xenotransplantation model. Taken together, our concept offers a novel platform for discovery of anti-metastasis drugs.
A bacterial signal transduction phosphorelay in the methanogenic archaeonMethanosarcina acetivorans
Authors: Sexauer Anne , Frankenberg-Dinkel Nicole
Published: March 2021

Signal transduction via two-component systems is a powerful tool for microorganisms to respond to environmental changes. Histidine kinases originating from Bacteria are the most common signaling enzymes and are also present in Archaea, but not in all phyla. A total of 124 bacterial-type histidine kinases and/or regulators were identified in a screen of 149 Euryarchaeota genomes, but little is known about the signal transfer and molecular regulation of these systems (1).

In this work, the hybrid kinase MA4377 from the methanogenic archaeonMethanosarcina acetivoranswas investigated (2, 3). MA4377 is a multidomain protein resembling a bacterial-type histidine kinase with two additional receiver domains at the C-terminus. Recombinant protein was employed to investigate the intra- and intermolecular phosphorelayin vitro. The kinase displays autophosphorylation activity of histidine residue 497. While no intramolecular phosphorelay was observed, the CheY-like receiver protein MA4376 was identified as part of the multi-component system that also seems to include the Msr-type transcription factor MA4375. This study reveals the presence andin vitrofunction of a bacterial-type hybrid histidine kinase integrated into an archaeal phosphorelay system.

Importance

Signal transduction enables organisms to rapidly react to changes in their surroundings. Different systems containing one-, two- or multiple-components are employed to sense and react to environmental changes. Most commonly, external perceived stimuli are converted into internal signals through protein phosphorylation. These systems are found in all domains of life but understood at different levels of complexity, the least being those from the domain of Archaea. By better elucidating the function of these early signal transduction systems, we will gain insight and understanding of the selection pressures on signal transduction pathways, and their evolution within the Archaea.
Recovery of high-qualitied Genomes from a deep-inland Salt Lake Using BASALT
Authors: Yu Ke , Qiu Zhiguang , Mu Rong , Qiao Xuejiao , Zhang Liyu , Lian Chun-Ang , Deng Chunfang , Wu Yang , Xu Zheng , Li Bing , Pan Baozhu , Zhang Yunzeng , Fan Lu , Liu Yong-xin , Cao Huiluo , Jin Tao , Chen Baowei , Wang Fan , Yan Yan , Xie Luhua , Zhou Lijie , Yi Shan , Chi Song , Zhang Chuanlun , Zhang Tong , Zhuang Weiqin
Published: March 2021

Metagenomic binning enables the in-depth characterization of microorganisms. To improve the resolution and efficiency of metagenomic binning, BASALT (Binning Across a Series of AssembLies Toolkit), a novel binning toolkit was present in this study, which recovers, compares and optimizes metagenomic assembled genomes (MAGs) across a series of assemblies from short-read, long-read or hybrid strategies. BASALT incorporates self-designed algorithms which automates the separation of redundant bins, elongate and refine best bins and improve contiguity. Evaluation using mock communities revealed that BASALT auto-binning obtained up to 51% more number of MAGs with up to 10 times better MAG quality from microbial community at low (132 genomes) and medium (596 genomes) complexity, compared to other binners such as DASTool, VAMB and metaWRAP. Using BASALT, a case-study analysis of a Salt Lake sediment microbial community from northwest arid region of China was performed, resulting in 426 non-redundant MAGs, including 352 and 69 bacterial and archaeal MAGs which could not be assigned to any known species from GTDB (ANI < 95%), respectively. In addition, two Lokiarchaeotal MAGs that belong to superphylum Asgardarchaeota were observed from Salt Lake sediment samples. This is the first time that candidate species from phylum Lokiarchaeota was found in the arid and deep-inland environment, filling the current knowledge gap of earth microbiome. Overall, BASALT is proven to be a robust toolkit for metagenomic binning, and more importantly, expand the Tree of Life.
Public science data suggest that fish is the most important factor in reducing small pond biodiversity in Czechia
Authors: Hulcr Jiri , Gomez Demian F.
Published: March 2021

Abstract

This project tested a public-science approach to the assessment of freshwater habitat quality via simple invertebrate sampling. We combined a mobile phone application and simple instruction to children to sample 50 ponds in Central Czechia, and we analyzed the data using a standard ecological statistics approach. Despite the limitation in scope and taxonomic precision, our data revealed the same patterns as academic studies of the same topic. Specifically, we conclude that the main cause of invertebrate community decline is fish overstocking, while diverse invertebrate communities require aquatic macrophytes. Pollution detectable by children has an effect on invertebrate community structure, but a different effect than fish has, and not as statistically robust. Importantly, almost all large ponds were found overstocked with fish; therefore, they support not more diversity than small ponds, but less, and serve as ecological traps. Our findings suggest that pond conservation should focus primarily on the restoration of aquatic vegetation, and that the most effective approach will be the removal of excessive fish.
Significance of the Wnt canonical pathway in radiotoxicity via oxidative stress of electron beam radiation and its molecular control in mice
Authors: Kumar Shashank , Fathima Eram , Khanum Farhath , S Malini Suttur
Published: March 2021

Radiation triggers the cell death events through signaling proteins, but the combined mechanism of events is unexplored. We intend to investigate how the combined cascade works throughout the radiation process and its significance over radiotoxicity. Thirty adult mice were irradiated with electron beam radiation, and five were served as a control (Non treated). Mice were sacrificed after post 24 hours and 30 days of irradiation. We assessed the oxidative stress parameter and mRNA profile (Liver, Kidney, spleen, and germ cells), sperm viability, and motility. The mRNA profile study established the network of combined cascade work during radiation to combat oxidative response and cell survival. The quantitative examination of mRNA uncovers unique critical changes in all mRNA levels in all the cases, particularly in germ cells. Recuperation was likewise seen in post 30 days radiation in the liver, spleen, and kidney followed by oxidative stress parameters, however not in germ cells. It proposes reproductive physiology is exceptionally sensitive towards radiation, even at the molecular level. It also suggests the suppression of Lef1/axin2 could be the main reason for permanent failure in the sperm function process. Post irradiation likewise influences the morphology of sperms. The decrease in mRNA level of Lef1, Axin2, survivin, Ku70 suggests radiation inhibits the Wnt canonical pathway and failure in DNA repair mechanism in a coupled manner. Likewise, the increase in BAX and BCL2 suggests apoptosis activation followed by the decreased expression of enzymatic antioxidants. In summary, controlled several interlinked cascades execute when body exposure to radiation may further be used in a study to counterpart and better comprehend medication focus on radiation treatment.
Tract-specific statistics based on diffusion-weighted probabilistic tractography
Authors: Reid Andrew T. , Camilleri Julia A. , Hoffstaedter Felix , Eickhoff Simon B.
Published: March 2021

Diffusion-weighted neuroimaging approaches provide rich evidence with which to estimate the structural integrity of white matter in vivo. Tract-based spatial statistics (TBSS), for instance, allows us to assess the spatial distribution of statistical tests performed on diffusion properties such as fractional anisotropy, which are proposed to reflect the integrity of white matter tracts. However, such methods do not provide a direct assessment of white matter integrity for connections between two specific regions of the brain. Here, we present a novel method for deriving tract-specific diffusion statistics, based upon arbitrarily-defined regions of interest. Our approach makes use of an empirically-derived population distribution based on probabilistic tractography, using the Nathan Kline Institute (NKI) Enhanced Rockland sample. We use a heuristic method to determine the most likely geometry of a path between two regions, if one exists, and express this as a spatial distribution. We then estimate the average orientation of streamlines traversing this path, at discrete distances along its trajectory, and compute the fraction of diffusion directed along this orientation for each participant. This allows us to obtain participant-wise metrics along the specific tract (tract-specific anisotropy; TSA), which can then be used to perform statistical analysis on any comparable population. Based on this method, we report both negative and positive associations between age and TSA for two networks derived from published meta-analytic studies (the “default mode” and “what-where” networks), along with more moderate sex differences and age-by-sex interactions in both networks.
In vivohigh-throughput screening of novel adeno-associated viral capsids targeting adult neural stem cells in the subventricular zone
Authors: Dehler Sascha , Kremer Lukas PM , Cerrizuela Santiago , Stiehl Thomas , Weinmann Jonas , Abendroth Heike , Kleber Susanne , Laure Alexander , Andari Jihad El , Anders Simon , Marciniak-Czochra Anna , Grimm Dirk , Martin-Villalba Ana
Published: March 2021

The adult mammalian brain entails a reservoir of neural stem cells (NSCs) generating glial cells and neurons. However, NSCs become increasingly quiescent with age, which hampers their regenerative capacity. New means are therefore required to genetically modify adult NSCs for re-enabling endogenous brain repair. Recombinant adeno-associated viruses (AAVs) are ideal gene therapy vectors due to an excellent safety profile and high transduction efficiency. We thus conducted a high-throughput screening of 177 intraventricularly injected barcoded AAV variants profiled by RNA sequencing. Quantification of barcoded AAV mRNAs identified two synthetic capsids, AAV9_A2 and AAV1_P5, both of which transduce active and quiescent NSCs. Further optimization of AAV1_P5 by judicious selection of promoter and dose of injected viral genomes enabled labeling of 30-60% of the NSC compartment, which was validated by FACS analyses and single cell RNA sequencing. Importantly, transduced NSC readily produced neurons. The present study identifies AAV variants with a high regional tropism towards the v-SVZ with high efficiency in targeting adult NSCs, thereby paving the way for preclinical testing of regenerative gene therapy.
Biosynthesis of benzoxazinoids in rye (Secale cerealeL.) – where does the story begin?
Authors: Rakoczy-Trojanowska Monika , Różańska Elżbieta , Święcicka Magdalena , Burza Wojciech , Bakera Beata , Kowalczyk Mariusz , Łotocka Barbara , Szabała Bartosz
Published: March 2021

According to current opinion, the first step of benzoxazinoids (BXs) synthesis, that is, the conversion of indole-3-glycerol phosphate to indole, occurs exclusively in the photosynthesising parts of plants. However, the results of our previous work and some other studies suggest that this process may also occur in the roots. In this study, we provide evidence that the first step of BXs synthesis does indeed occur in the roots of rye seedlings. We detectedScBx1transcripts, BX1 enzyme, and six BXs (2-hydroxy-1,4-benzoxazin-3-one, 2,4-dihydroxy-1,4-benzoxazin-3-one, (2R)-2-O-β-d-glucopyranosyl-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one glucoside, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one glucoside, and 6-methoxy-2-benzoxazolinone) in the roots developed from seeds deprived of the coleoptile at 2 days after sowing (i.e., roots without contact with aerial parts). In roots regeneratedin vitro, bothScBx1transcripts and BX1 enzyme were detected at a low but still measurable levels. Thus, BXs are able to be synthesised in both the roots and above-ground parts of rye plants.

Highlight

The first step benzoxazinoids synthesis occurs in both the above-ground parts and roots of rye plants. Benzoxazinoids can be synthesisedde novoin roots, independently of plants’ photosynthesising parts.
Non-academic employment and matching satisfaction among PhD graduates with high intersectoral mobility potential
Authors: Alfano Vincenzo , Gaeta Giuseppe , Pinto Mauro
Published: March 2021

Purpose

This paper contributes to the empirical analysis of PhD holders' transition into the non-academic labor market (i.e. their intersectoral mobility). The research focuses on doctoral graduates specialized in a field of study supposed to have notable non-academic applications, namely Industrial and Information Engineering. We inspect whether these doctoral graduates experience lower satisfaction with PhD knowledge use on the job when they work outside universities and non-public research centers.

Design/methodology/approach

We use cross-sectional survey data collected by the Italian National Institute of Statistics in 2014. Ordinary least squares and ordered logit analyses provide baseline results; furthermore, we apply a multinomial endogenous treatment model to control for potential bias arising from self-selection into employment sectors.

Findings

We find evidence that for PhD holders Industrial and Information Engineering being employed in the industrial and services sector implies lower satisfaction with the use of doctoral knowledge than that reported by their counterparts working in universities or public research centers.

Originality/value

These results complement and extend previous evidence about PhD holders' career outcomes by focusing on the intersectoral mobility issue and on a specific group of doctoral graduates whose intersectoral mobility potential is expected to be high. Our findings call for policies that might trigger a better alignment between doctoral education and non-academic jobs.
Evaluating the quality of reported outcomes for microsurgical TESE in men with non‐obstructive azoospermia: A methodological analysis
Authors: Ernandez John , Berk Brittany , Han Tracy , Abou Ghayda Ramy , Kathrins Martin
Published: March 2021

Background

Publications of microsurgical testicular sperm extraction (mTESE) techniques and outcomes are heterogeneous, which may limit creation of best surgical practices.

Objective

To study the quality and heterogeneity of published mTESE outcomes via a methodological analysis.

Materials/Methods

A systematic methodological analysis of all published literature on the use of mTESE in men with non‐obstructive azoospermia from 1999 to the July 2020 was performed. PubMed and MEDLINE searches were performed using the search terms “microdissection TESE OR microsurgical TESE.” Publications were evaluated on their reporting of pre‐operative factors, intraoperative techniques, surgical and clinical outcomes, and adverse events.

Results

Fifty‐five studies met inclusion criteria. Surgical technique and sperm retrieval rates were the most reported criteria. Reporting on the presence of an embryologist intraoperatively was observed in approximately 30% of articles, while other procedural details including method of sperm quantification, quantity retrieved, and number of cryopreserved vials were observed in fewer than 10% of articles. Clinical outcomes, including pregnancy rates and live birth rates, were reported in fewer than 40% of the articles. Fetal outcomes including fetal and neonatal anomalies were rarely reported. Fetal growth restriction, preterm delivery, small or large for gestational age, and NICU admissions were never reported.

Conclusion

There are inconsistencies in reporting quality of mTESE outcomes, specifically a lack of information on the quantity and quality of sperm retrieved, the role of embryology intraoperatively, and clinical outcomes, such as live birth rate and fetal anomalies. These gaps may guide development of standardized reporting guidelines to better assess and compare clinical outcomes across institutions and maintain focus on couples‐centric fertility outcomes in future mTESE studies.
Circulating anti-citrullinated protein antibodies containing secretory component are prognostic for arthritis onset in at-risk patients
Authors: Roos Ljungberg K , Martinsson K , Wetterö J , Svärd A , Kastbom A
Published: March 2021

Autoantibodies related to rheumatoid arthritis (RA), such as anti-citrullinated protein antibodies (ACPA), are often detectable in the preclinical period years before arthritis onset. However, events triggering arthritis development remain incompletely known. We aimed to determine whether ACPA isotype levels are prognostic for arthritis development in patients presenting with immunoglobulin (Ig)G ACPA and musculoskeletal pain. Study participants (n = 82) had musculoskeletal pain of any sort and duration and a positive IgG ACPA test. None of the patients had arthritis upon clinical examination at baseline, but during follow-up (mean = 6 years), 48% developed at least one arthritic joint. IgG, IgA, IgM and secretory component (SC)-containing ACPA was measured in longitudinally collected serum samples. Cox regression analysis was performed to test the prognostic value of baseline antibody levels and changes over time. All analysed ACPA isotype levels were associated with arthritis development in univariable Cox regression analysis. In multivariable analysis, baseline SC ACPA levels were independently prognostic for arthritis development in multivariable analysis [hazard ratio (HR) = 1·006, 95% confidence interval (CI) = 1·001–1·010, P = 0·012]. There were no significant changes in ACPA isotype levels over time, and no significant association between changes over time and arthritis development. In this prospective longitudinal study, baseline serum SC ACPA levels, but neither IgG, IgA nor IgM ACPA are prognostic for future arthritis development. Repeated measurement of ACPA isotypes do not bring additional prognostic value. The results reinforce a mucosal connection in RA development and encourage further exploration of the mechanisms underlying secretory ACPA formation as a trigger for arthritis development.