bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting a cysteine protease from a pathobiont alleviates experimental arthritis
Authors: Peng Hsin-Yi , Chen Shih-Yao , Siao Shih-Hong , Chang Jinghua Tsai , Xue Ting-Yin , Lee Yi-Hsuan , Jan Ming-Shiou , Tsay Gregory J. , Zouali Moncef
Published: May 2020

Background

Several lines of evidence suggest that the pathobiont Porphyromonas gingivalis is involved in the development and/or progression of auto-inflammatory diseases. This bacterium produces cysteine proteases, such as gingipain RgpA, endowed with the potential to induce significant bone loss in model systems and in patients.

Objective

We sought to gain further insight into the role of this pathobiont in rheumatoid arthritis (RA) and to identify novel therapeutic targets for auto-inflammatory diseases.

Methods

We profiled the antibody response to RgPA-specific domains in patient sera. We also tested the potential protective effects of RgpA domains in an experimental arthritis model.

Results

Pre-immunization of rats with purified recombinant RgpA domains alleviated arthritis in the joints of the rodents and reduced bone erosion. Using a functional genomics approach at both the mRNA and protein levels, we report that the pre-immunizations reduced arthritis severity by impacting a matrix metalloprotease characteristic of articular injury, a chemokine known to be involved in recruiting inflammatory cells, and three inflammatory cytokines. Finally, we identified an amino acid motif in the RgpA catalytic domain of P. gingivalis that shares sequence homology with type II collagen.

Conclusion

We conclude that pre-immunization against gingipain domains can reduce the severity of experimentally induced arthritis. We suggest that targeting gingipain domains by pre-immunization, or, possibly, by small-molecule inhibitors, could reduce the potential of P. gingivalis to translocate to remote tissues and instigate and/or exacerbate pathology in RA, but also in other chronic inflammatory diseases.
Type IV secretion of Helicobacter pylori CagA into oral epithelial cells is prevented by the absence of CEACAM receptor expression
Authors: Tegtmeyer Nicole , Ghete Tabita Denisia , Schmitt Verena , Remmerbach Torsten , Cortes Maria Celeste C. , Bondoc Edgardo M. , Graf Hans-Ludwig , Singer Bernhard B. , Hirsch Christian , Backert Steffen
Published: May 2020

Background

Helicobacter pylori typically colonizes the human stomach, but it can occasionally be detected in the oral cavity of infected persons. Clinical outcome as a result of gastric colonization depends on presence of the pathogenicity island cagPAI that encodes a type-IV secretion system (T4SS) for translocation of the effector protein CagA and ADP-heptose. Upon injection into target cells, CagA is phosphorylated, which can be demonstrated by in vitro infection of the gastric epithelial cell line AGS, resulting in cell elongation. Here we investigated whether H. pylori can exert these responses during interaction with cells from the oral epithelium. To this purpose, three oral epithelial cell lines, HN, CAL-27 and BHY, were infected with various virulent wild-type H. pylori strains, and CagA delivery and ADP-heptose-mediated pro-inflammatory responses were monitored.

Results

All three oral cell lines were resistant to elongation upon infection, despite similar bacterial binding capabilities. Moreover, T4SS-dependent CagA injection was absent. Resistance to CagA delivery was shown to be due to absence of CEACAM expression in these cell lines, while these surface molecules have recently been recognized as H. pylori T4SS receptors. Lack of CEACAM expression in HN, CAL-27 and BHY cells was overcome by genetic introduction of either CEACAM1, CEACAM5, or CEACAM6, which in each of the cell lines was proven sufficient to facilitate CagA delivery and phosphorylation upon H. pylori infection to levels similar to those observed with the gastric AGS cells. Pro-inflammatory responses, as measured by interleukin-8 ELISA, were induced to high levels in each cell line and CEACAM-independent.

Conclusions

These results show that lack of CEACAM receptors on the surface of the oral epithelial cells was responsible for resistance to H. pylori CagA-dependent pathogenic activities, and confirms the important role for the T4SS-dependent interaction of these receptors with H. pylori in the gastric epithelium.
Correction to: Validity and reliability of a dish-based semi-quantitative food frequency questionnaire for assessment of energy and nutrient intake among Iranian adults
Authors: Doustmohammadian Azam , Amini Maryam , Esmaillzadeh Ahmad , Omidvar Nasrin , Abtahi Mitra , Dadkhah-Piraghaj Monireh , Nikooyeh Bahareh , Neyestani Tirang R.
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Adaptive middleware in go - a software architecture-based approach
Authors: Rosa Nelson , Cavalcanti David , Campos Gláucia , Silva André
Published: May 2020

Adaptive middleware is essential for developing distributed systems in several applications domains. The design and implementation of this kind of middleware, however, it is still a challenge due to general adaptation issues, such as When to adapt? Where to include the adaptation code? What to adapt?, and How to guarantee safe adaptations?. Current solutions commonly face these challenges at the implementation level and do not focus on the safety aspects of the adaptation. This paper proposes a holistic solution implemented in Go programming language for developing adaptive middleware centred on the adoption of software architecture principles combined with lightweight use of formalisms. Software architecture concepts work as an enabling approach for structuring and adapting the middleware. Meanwhile, the formalisation helps in providing some guarantees before and during the middleware execution. The proposed solution is evaluated by implementing an adaptive middleware and comparing its performance against existing middleware systems. As shown in the experimental evaluation, the proposed solution enables us to design and implement safe adaptive middleware systems without compromising their performance.
Long-term safety and tolerability of atabecestat (JNJ-54861911), an oral BACE1 inhibitor, in early Alzheimer’s disease spectrum patients: a randomized, double-blind, placebo-controlled study and a two-period extension study
Authors: Novak Gerald , Streffer Johannes Rolf , Timmers Maarten , Henley David , Brashear H. Robert , Bogert Jennifer , Russu Alberto , Janssens Luc , Tesseur Ina , Tritsmans Luc , Van Nueten Luc , Engelborghs Sebastiaan
Published: May 2020

Background

Atabecestat, a potent brain-penetrable inhibitor of BACE1 activity that reduces CSF amyloid beta (Aβ), was developed for oral treatment for Alzheimer’s disease (AD).

The long-term safety and effect of atabecestat on cognitive performance in participants with predementia AD in two phase 2 studies were assessed.

Methods

In the placebo-controlled double-blind parent ALZ2002 study, participants aged 50 to 85 years were randomized (1:1:1) to placebo or atabecestat 10 or 50 mg once daily (later reduced to 5 and 25 mg) for 6 months. Participants entered ALZ2004, a 12-month treatment extension with placebo or atabecestat 10 or 25 mg, followed by an open-label phase. Safety, changes in CSF biomarker levels, brain volume, and effects on cognitive performance were assessed.

Results

Of 114 participants randomized in ALZ2002, 99 (87%) completed, 90 entered the ALZ2004 double-blind phase, and 77 progressed to the open-label phase. CSF Aβ fragments and sAPPβ were reduced dose-proportionately. Decreases in whole brain and hippocampal volumes were greater in participants with mild cognitive impairment (MCI) due to AD than in preclinical AD, but were not affected by treatment. In ALZ2004, change from baseline in RBANS trended toward worse scores for atabecestat versus placebo. Elevated liver enzyme adverse events reported in 12 participants on atabecestat resulted in dosage modification and increased frequency of safety monitoring. Treatment discontinuation normalized ALT or AST in all except one with pretreatment elevation, which remained mildly elevated. No case met ALT/AST > 3× ULN and total bilirubin > 2× ULN (Hy’s law).

Conclusion

Atabecestat was associated with trend toward declines in cognition, and elevation of liver enzymes.

Trial registration

ALZ2002: ClinicalTrials.gov, NCT02260674, registered October 9, 2014; ALZ2004: ClinicalTrials.gov, NCT02406027, registered April 1, 2015.
The meta-memory ratio: a new cohort-independent way to measure cognitive awareness in asymptomatic individuals at risk for Alzheimer’s disease
Authors:   for ADNI; for the INSIGHT-preAD study group, Gagliardi Geoffroy , Houot Marion , Cacciamani Federica , Habert Marie-Odile , Dubois Bruno , Epelbaum Stéphane
Published: May 2020

Background

Lack of awareness of cognitive decline (ACD) has been described at the preclinical and prodromal stages of Alzheimer’s disease (AD). In this study, we introduced a meta-memory ratio (MMR) and explored how it is associated with neuroimaging AD biomarkers in asymptomatic individuals at risk for AD.

Method

Four hundred forty-eight cognitively healthy participants from two cohorts of subjective memory complainers (INSIGHT-PreAD and ADNI) were included. Regression models were used to assess the impact of AD biomarkers on the MMR.

Result

In both cohorts, there was a significant quadratic effect of cerebral amyloidosis on the MMR value. In particular, participants had a high ACD up to the amyloid positivity threshold, above which a decrease of ACD was eventually observed as the amyloid load increased.

Conclusion

This nonlinear evolution of ACD in very early AD must be taken into account in clinical care and for trial enrollment as well.
Prevalence and cumulative incidence of autism spectrum disorders and the patterns of co-occurring neurodevelopmental disorders in a total population sample of 5-year-old children
Authors: Saito Manabu , Hirota Tomoya , Sakamoto Yui , Adachi Masaki , Takahashi Michio , Osato-Kaneda Ayako , Kim Young Shin , Leventhal Bennett , Shui Amy , Kato Sumi , Nakamura Kazuhiko
Published: May 2020

Backgrounds

Whether there is a true increase in autism spectrum disorder (ASD) frequency or not remains unclear. Additionally, the rates of co-existing neurodevelopmental disorders (NDD) in a total population sample has not been fully examined before. Therefore, using a total population sample in Japan, we aimed to estimate the prevalence and cumulative incidence of autism spectrum disorder (ASD) annually, to determine whether there is a true increase in ASD prevalence by estimating the cumulative incidence of ASD annually, and to examine the rates of co-existing neurodevelopmental disorders (NDD).

Method

In this cross-sectional sequential design study, all 5-year-old children in the catchment area underwent the screening annually from the year 2013–2016. Screen-positive children were invited to participate in a comprehensive assessment, including child and parent interview, behavioral observation, and cognitive and motor function testing. All cases were reviewed by a multidisciplinary research team.

Results

Caregivers of 3954 children returned the screening, among which 559 children underwent the assessment with 87 children receiving an ASD diagnosis. Adjusted ASD prevalence was 3.22% (95% confidence interval (CI) 2.66–3.76%). The male to female ratio of the crude prevalence was 2.2:1. The cumulative incidence of ASD up to 5 years of age for the total study years was 1.31% (95% CI 1.00–1.62%). A generalized linear model revealed no significant linear trends in 5-year cumulative incidence over the study years. Only 11.5% of children had ASD alone; the remaining 88.5% were found to have at least one co-existing NDD.

Limitations

Modest sample size for a total population study.

Conclusions

Our findings demonstrate the stability of the 5-year cumulative incidence of ASD, implying no true rise in ASD incident cases over the 4-year study period in the study catchment area. High rates of co-existing NDDs reflect the importance of investigating broad developmental challenges in children with ASD.
Fluorescence labeling of a NaV1.7-targeted peptide for near-infrared nerve visualization
Authors: Gonzales Junior , Pirovano Giacomo , Chow Chun Yuen , de Souza Franca Paula Demetrio , Carter Lukas M. , Klint Julie K. , Guru Navjot , Lewis Jason S. , King Glenn F. , Reiner Thomas
Published: May 2020

Background

Accidental peripheral nerve injury during surgical intervention results in a broad spectrum of potentially debilitating side effects. Tissue distortion and poor visibility can significantly increase the risk of nerve injury with long-lasting consequences for the patient. We developed and characterized Hs1a-FL, a fluorescent near-infrared molecule for nerve visualization in the operating theater with the aim of helping physicians to visualize nerves during surgery. Hs1a was derived from the venom of the Chinese bird spider, Haplopelma schmidti, and conjugated to Cy7.5 dye. Hs1a-FL was injected intravenously in mice, and harvested nerves were imaged microscopically and with epifluorescence.

Results

Hs1a-FL showed specific and stable binding to the sodium channel NaV1.7, present on the surface of human and mouse nerves. Hs1a-FL allowed epifluorescence visualization of sciatic mouse nerves with favorable nerve-to-muscle contrast.

Conclusions

Fluorescent NaV1.7-targeted tracers have the potential to be adopted clinically for the intraoperative visualization of peripheral nerves during surgery, providing guidance for the surgeon and potentially improving the standard of care.
Long-term Ashtanga yoga practice decreases medial temporal and brainstem glucose metabolism in relation to years of experience
Authors: van Aalst June , Ceccarini Jenny , Schramm Georg , Van Weehaeghe Donatienne , Rezaei Ahmadreza , Demyttenaere Koen , Sunaert Stefan , Van Laere Koen
Published: May 2020

Background

Yoga is increasingly popular worldwide with several physical and mental benefits, but the underlying neurobiology remains unclear. Whereas many studies have focused on pure meditational aspects, the triad of yoga includes meditation, postures, and breathing. We conducted a cross-sectional study comparing experienced yoga practitioners to yoga-naive healthy subjects using a multiparametric 2 × 2 design with simultaneous positron emission tomography/magnetic resonance (PET/MR) imaging.

Methods

18F-FDG PET, morphometric and diffusion tensor imaging, resting state fMRI, and MR spectroscopy were acquired in 10 experienced (4.8 ± 2.3 years of regular yoga experience) yoga practitioners and 15 matched controls in rest and after a single practice (yoga practice and physical exercise, respectively).

Results

In rest, decreased regional glucose metabolism in the medial temporal cortex, striatum, and brainstem was observed in yoga practitioners compared to controls (p < 0.0001), with a significant inverse correlation of resting parahippocampal and brainstem metabolism with years of regular yoga practice (ρ < − 0.63, p < 0.05). A single yoga practice resulted in significant hypermetabolism in the cerebellum (p < 0.0001). None of the MR measures differed, both at rest and after intervention.

Conclusions

Experienced yoga practitioners show regional long-term decreases in glucose metabolism related to years of practice. To elucidate a potential causality, a prospective longitudinal study in yoga-naive individuals is warranted.
Research on data mining algorithm of logistics time series based on intelligent integrated network structure
Authors: Zhang Zhengyi , Cui Jian
Published: May 2020

With the continuous development of information, big data analysis has become important and dependent technical means-increasingly in various fields. By data mining through time series, the development regular of the object could be grasped, so we could predict its future development trend. Based on the intelligent integration architecture, a new algorithm of bi-weighted support vector machines (SVM) based on category weighting, and feature weighting was proposed to solve the problem of unbalanced samples in time series. In the non-balanced sample set classification, the recognition ability of the traditional classification method was low; the supported vector machine as classifier was taken in the new algorithm based on cost-sensitive learning, and different weighting coefficients to less and more samples were given, and Gauss kernel function with the weight coefficients of different features was reconstructed, thus the recognition ability of less samples was improved. In the experiment, classification accuracy, g-mean, f-measure, TP, and FP were selected as evaluation indexes, indicating that the two-weighted SVM algorithm is effective in the classification of non-balanced sample sets.
Hybrid WGWO: whale grey wolf optimization-based novel energy-efficient clustering for EH-WSNs
Authors: Rathore Rajkumar Singh , Sangwan Suman , Prakash Shiv , Adhikari Kabita , Kharel Rupak , Cao Yue
Published: May 2020

The energy harvesting methods enable WSNs nodes to last potentially forever with the help of energy harvesting subsystems for continuously providing energy, and storing it for future use. The energy harvesting techniques can use various potential sources of energy, such as solar, wind, mechanical, and variations in temperature. Energy-constrained sensor nodes are small in size. Therefore, some mechanisms are required to reduce energy consumption and consequently to improve the network lifetime. The clustering mechanism is used for energy efficiency in WSNs. In the clustering mechanism, the group of sensor nodes forms the clusters. The performance of the clustering process depends on various factors such as the optimal number of clusters formation and the process of cluster head selection. In this paper, we propose a hybrid whale and grey wolf optimization (WGWO)-based clustering mechanism for energy harvesting wireless sensor networks (EH-WSNs). In the proposed research, we use two meta-heuristic algorithms, namely, whale and grey wolf to increase the effectiveness of the clustering mechanism. The exploitation and exploration capabilities of the proposed hybrid WGWO approach are much higher than the traditional various existing metaheuristic algorithms during the evaluation of the algorithm. This hybrid approach gives the best results. The proposed hybrid whale grey wolf optimization-based clustering mechanism consists of cluster formation and dynamically cluster head (CH) selection. The performance of the proposed scheme is compared with existing state-of-art routing protocols.
α-ψ-contractions and solutions of a q-fractional differential inclusion with three-point boundary value conditions via computational results
Authors: Etemad Sina , Rezapour Shahram , Samei Mohammad Esmael
Published: May 2020

We review the existence of solutions for a three-point nonlinear q-fractional differential equation and also its related inclusion. In this way, we use α-ψ-contractions and multifunctions. Also, we provide two examples to illustrate our main results. Finally by providing some algorithms and tables, we give some numerical computations for the results.
Validity and reliability of the Greek version of Implementation Leadership Scale (ILS)
Authors: Mandrou Eleni , Tsounis Andreas , Sarafis Pavlos
Published: May 2020

Background

The need for developing pragmatic and reliable measures that affect evidence-based practice has been highlighted in organizational studies. The aim of the current study is to evaluate the psychometric properties of the Greek version of Implementation Leadership Scale (ILS). ILS is a brief and effective tool for measuring leadership when implementing evidence based practices.

Methods

The translation process followed World Health Organization guidelines. Face and content validity were examined. Then, the psychometric properties of ILS were tested with a sample of 143 nurses and midwifes working in a private Greek hospital. Confirmatory Factor Analyses for structural validity testing, Pearson coefficient for convergent and discriminant validity testing as well as internal consistency analysis for reliability testing were conducted. Quality of leadership scale from COPSOQ II and Organizational Climate Measure were used for assessing convergent and discriminant validity, respectively.

Results

Greek version of ILS show good face and content validity. CFA results (x2 = 100. 69 (50); CFI = 0.93; GFI = 0.83; RMSEA = 0.06) confirmed the four-factor structure of the scale (Proactive, Knowledgeable, Supportive and Perseverant leadership). The internal consistency was excellent (a = 0.94 for total scale and between 0.85 and 0.91 for subscales). Analyses also revealed good convergent and discriminant validity.

Conclusions

The findings suggest that the Greek Version of ILS is a valid and reliable tool for measuring leadership of evidence based practices implementation. However, further research for assessing its psychometric properties in various samples and more professional groups is suggested.
Feasibility of a virtual reality-based interactive feedback program for modifying dysfunctional communication: a preliminary study
Authors: Kim Junhyung , Jung Young Hoon , Shin Yu-Bin , Kim Min-Kyeong , Eom Hyojung , Kim Eunjoo , Kim Joohan , Kim Jae-Jin
Published: May 2020

Background

Functional communication is vital in many areas of daily life, and modifying dysfunctional communication has been emphasized in various social areas, including family and school. The present preliminary study addressed the feasibility of a virtual reality (VR)-based interactive feedback program for the modification of dysfunctional communication.

Methods

Thirty-seven healthy young males completed psychological assessments associated with functional communication and participated in the VR-based program, consisting of the three tasks of ‘exploring the communication style,’ ‘practicing functional communication,’ and ‘expressing empathy.’ Behavioral parameters were recorded based on the participants’ choices among available options and the visual analog scale scores that resulted in responses to questions in the tasks.

Results

Participants completed the program without dropping-out and reported 10.76 (SD, 9.66) in the Simulator Sickness Questionnaire and 106.97 (SD, 16.66) in the Presence Questionnaire. In exploring the communication style, there was no difference between the dysfunction level-with family and dysfunction level-with a friend, but only the dysfunction level-with family showed significant correlations with the level of communication with parents. In practicing functional communication, the communication scores with the placating, blaming, and computing styles significantly increased according to the repetition of trials. In expressing empathy, the empathetic feeling score was negatively correlated with the perspective-taking score, whereas the emotional intensity score was positively correlated with the level of differentiation of the self.

Conclusion

These results suggest that the program may have a tolerable level of cybersickness, an adequate level of presence, an improvement in the behavioral parameters that may reflect the important aspects of communication, and a proper reflection of psychological states or interpersonal characteristics. The use of this program can be an important starting point for the development of a more convenient method for delivering VR programs designed to modify dysfunctional communication, which can further increase computerized dissemination.
NMR structure and bactericidal activity of KR-12 analog derived from human LL-37 as a potential cosmetic preservative
Authors: Yun Hyosuk , Min Hye Jung , Lee Chul Won
Published: May 2020

KR-12 was derived from the human antimicrobial peptide, LL-37. KR-12 maintains the antimicrobial activity of LL-37 and has low toxicity against human cells, thereby showing a high potential for various applications. In this study, the three-dimensional structure of KR-12 analog (KR-12-pa) was determined by solution NMR spectroscopy. The NMR structure of KR-12-pa revealed a nearly perfect amphipathic α-helical structure composed of multiple hydrophobic and positively charged residues. The minimal inhibitory concentration of KR-12-pa for various bacterial and yeast cells suggested that KR-12-pa has a much stronger antimicrobial activity than commercial cosmetic preservatives. In addition, KR-12-pa in cosmetic formulations showed much stronger bactericidal effects than conventional cosmetic preservatives and very low cytotoxicity to mammalian cells. These results suggest that KR-12-pa is applicable as a cosmetic preservative.
18F-FDG PET/CT based spleen to liver ratio associates with clinical outcome to ipilimumab in patients with metastatic melanoma
Authors: Wong Annie , Callahan Jason , Keyaerts Marleen , Neyns Bart , Mangana Johanna , Aberle Susanne , Herschtal Alan , Fullerton Sonia , Milne Donna , Iravani Amir , McArthur Grant A. , Hicks Rodney J.
Published: May 2020

Background

Immune checkpoint blockade such as ipilimumab and anti-PD1 monoclonal antibodies have significantly improved survival in advanced melanoma. Biomarkers are urgently needed as a majority of patients do not respond, despite treatment-related toxicities. We analysed pre-treatment 18F-fluorodeoxyglucose positron emission tomography/computerised tomography (FDG PET/CT) parameters to assess its correlation with patient outcome.

Methods

This retrospective study evaluated pre-treatment FDG PET/CT scans in a discovery cohort of patients with advanced melanoma treated with ipilimumab or anti-PD1. Pre-treatment scans were assessed for maximum tumoral standardised uptake value (SUVmax), metabolic tumour volume (MTV) and spleen to liver ratio (SLR). Progression-free survival (PFS) and overall survival (OS) were characterised and modelled using univariable and multivariable analyses. Correlation of SLR and OS was validated in an independent cohort. Blood parameters and stored sera of patients from the discovery cohort was analysed to investigate biological correlates with SLR.

Results

Of the 90 evaluable patients in the discovery cohort: 50 received ipilimumab monotherapy, 20 received anti-PD1 monotherapy, and 20 patients received ipilimumab followed by anti-PD1 upon disease progression. High SLR > 1.1 was associated with poor PFS (median 1 vs 3 months; HR 3.14, p = 0.008) for patients treated with ipilimumab. High SLR was associated with poor OS after ipilimumab (median 1 vs 21 months; HR 5.83, p = 0.0001); as well as poor OS after first line immunotherapy of either ipilimumab or anti-PD1 (median 1 vs 14 months; HR 3.92, p = 0.003). The association of high SLR and poor OS after ipilimumab was validated in an independent cohort of 110 patients (median 2.3 months versus 11.9 months, HR 3.74). SLR was associated with poor OS in a multi-variable model independent of stage, LDH, absolute lymphocyte count and MTV.

Conclusions

Pre-treatment Spleen to liver ratio (SLR) > 1.1 was associated with poor outcome after ipilimumab in advanced melanoma. This parameter warrants prospective evaluation.
Development of nuclear SSR and chloroplast genome markers in diverse Liriodendron chinense germplasm based on low-coverage whole genome sequencing
Authors: Li Bin , Lin Furong , Huang Ping , Guo Wenying , Zheng Yongqi
Published: May 2020

Background

Liriodendron chinense ranges widely in subtropical China and northern Vietnam; however, it inhabits several small, isolated populations and is now an endangered species due to its limited seed production. The objective of this study was to develop a set of nuclear SSR (simple sequence repeats) and multiple chloroplast genome markers for genetic studies in L. chinense and their characterization in diverse germplasm.

Results

We performed low-coverage whole genome sequencing of the L. chinense from four genotypes, assembled the chloroplast genome and identified nuclear SSR loci by searching in contigs for SSR motifs. Comparative analysis of the four chloroplast genomes of L. chinense revealed 45 SNPs, 17 indels, 49 polymorphic SSR loci, and five small inversions. Most chloroplast intraspecific polymorphisms were located in the interspaces of single-copy regions. In total, 6147 SSR markers were isolated from low-coverage whole genome sequences. The most common SSR motifs were dinucleotide (70.09%), followed by trinucleotide motifs (23.10%). The motif AG/TC (33.51%) was the most abundant, followed by TC/AG (25.53%). A set of 13 SSR primer combinations were tested for amplification and their ability to detect polymorphisms in a set of 109 L. chinense individuals, representing distinct varieties or germplasm. The number of alleles per locus ranged from 8 to 28 with an average of 21 alleles. The expected heterozygosity (He) varied from 0.19 to 0.93 and the observed heterozygosity (Ho) ranged from 0.11 to 0.79.

Conclusions

The genetic resources characterized and tested in this study provide a valuable tool to detect polymorphisms in L. chinense for future genetic studies and breeding programs.
Genome-wide variations analysis of sorghum cultivar Hongyingzi for brewing Moutai liquor
Authors: Zhou Lingbo , Wang Can , Gao Xu , Ding Yanqing , Cheng Bin , Zhang Guobing , Cao Ning , Xu Yan , Shao Mingbo , Zhang Liyi
Published: May 2020

Background

Hongyingzi is a sorghum (Sorghum bicolorL. Moench) cultivar for brewing Moutai liquor. For an overall understanding of the whole genome of Hongyingzi, we performed whole-genome resequencing technology to reveal its comprehensive variations.

Results

Compared with the BTx623 reference genome, we uncovered 1,885,774 single nucleotide polymorphisms (SNPs), 309,381 small fragments insertions and deletions (Indels), 31,966 structural variations (SVs), and 217,273 copy number variations (CNVs). These alterations conferred 29,614 gene variations. It was also predicted that 35 gene variations were related to the multidrug and toxic efflux (MATE) transporter, chalcone synthase (CHS), ATPase isoform 10 (AHA10) transporter, dihydroflavonol-4-reductase (DFR), the laccase 15 (LAC15), flavonol 3′-hydroxylase (F3′H), flavanone 3-hydroxylase (F3H),O-methyltransferase (OMT), flavonoid 3′5′ hydroxylase (F3′5′H), UDP-glucose:sterol-glucosyltransferase (SGT), flavonol synthase (FLS), and chalcone isomerase (CHI) involved in the tannin synthesis.

Conclusions

These results would provide theoretical supports for the molecular markers developments and gene function studies related to the tannin synthesis, and the genetic improvement of liquor-making sorghum based on the genome editing technology.
The puzzle of spontaneous versus traumatic intracranial hemorrhages
Authors: Quiñones-Ossa Gabriel Alexander , Durango-Espinosa Yeider , Padilla-Zambrano Huber , Moscote-Salazar Luis Rafael , Keni Ravish , Deora Harsh , Agrawal Amit
Published: May 2020

Intracerebral hemorrhage is hemorrhage occurring in the brain that can occur because of immediate trauma or structural disease process. The age-standardized mortality rate is decreasing worldwide especially in the past 20 years, but the number of cases and incidence along with number of disability-adjusted life-years and deaths keeps rising. Despite having half the incidence as ischemic stroke, intracerebral hemorrhage (traumatic or spontaneous) causes more morbidity and mortality than ischemic stroke and yet an established strategy for treatment on the lines of reperfusion therapy is a far-fetched dream. A selective review of all relevant articles covering recent treatment options and guidelines along with major emphasis of the surgical aspect and pathophysiology has been done. Complete literature review and differences between management of traumatic and spontaneous hemorrhage were sought and discussed. A pathophysiological basis of management should be followed for both these different yet similar pathologies. Understanding the etiology reveals a somewhat clearer picture regarding treatment of this highly unfortunate and devastating disease. Current interest is focused on the surgical management of the disease with the pathophysiology often been forgotten.
Fine structure of the cardiac muscle cells in the orb-web spider Nephila clavata
Authors: Sun Yan , Kim Hyo-Jeong , Moon Myung-Jin
Published: May 2020

The fine structural characteristics of cardiac muscle cells and its myofibril organization in the orb web spider N. clavata were examined by transmission electron microscopy. Although myofibril striations are not remarkable as those of skeletal muscles, muscle fibers contain multiple myofibrils, abundant mitochondria, extensive sarcoplasmic reticulum and transverse tubules (T-tubules). Myofibrils are divided into distinct sarcomeres defined by Z-lines with average length of 2.0 μm, but the distinction between the A-band and the I-bands is not clear due to uniform striations over the length of the sarcomeres. Dyadic junction which consisted of a single T-tubule paired with a terminal cisterna of the sarcoplasmic reticulum is found mainly at the A-I level of sarcomere. Each cell is arranged to form multiple connections with neighboring cells through the intercalated discs. These specialized junctions include three types of intercellular junctions: gap junctions, fascia adherens and desmosomes for heart function. Our transmission electron microscopy (TEM) observations clearly show that spider’s cardiac muscle contraction is controlled by neurogenic rather than myogenic mechanism since each cardiac muscle fiber is innervated by a branch of motor neuron through neuromuscular junctions.
Traditional foods and beverages in Eastern Tigray of Ethiopia
Authors: Tadesse Nigussie Seboka , Beyene Girum Faris , Hordofa Tesfaye Bekele , Hailu Ashenafi Ayenew
Published: May 2020

Ethiopia is a multiethnic country with diverse cultural practices to prepare foods and beverages having significant contributions in socioeconomic development. Contrary, comprehensive documentation of the products, associated knowledge, and their sociocultural roles is incomplete. In this survey, thirteen typical traditional foods (two fermented and eleven non-fermented) and five traditional beverages (four fermented and one non-fermented) were listed referring the local community of East Tigray. The noted traditional foods/beverages are known for their social and cultural values in the local community, and they are exercised following celebrity events. They are prepared often from barley (Hordeum vulgare), peas (Pisum sativum), wheat (Triticum aestivum), buckthorn (Rhamnus prinoides), maize (Zea mays), sorghum (Sorghum bicolor), and teff (Eragrostis tef). Some of the dishes/drinks such as Ambasha, Ebist, Gaa’t, Tihelo, Beso, Zikizuko, Abaekah, Duqua, Suwa, Mes, and Tahetah are well-acknowledged for their health and economic benefits. Others, like Birkuta and sola, are used to survive a long journey and looming drought. To conclude, this article presents a list of traditional foods and beverages which are potentially applicable in modern food or beverage industries and can contribute for global healthy diet.
Male Sex Hormone affection in patients with Tramadol dependance
Authors: Darweesh Alaa Eldin M. , Khalifa Hossam , Gabra Romany H. , Fahim Mena M.
Published: May 2020

Background

Tramadol is a centrally active synthetic opioid analgesic that is used extensively among Egyptian males for premature ejaculation as a self-medication.

The present work conducted to outline male sex hormone affection in patients with tramadol dependence and its relation to sexual satisfaction.

Results

Tramadol-dependent patients have significantly lower mean serum level of testosterone compared to the control group and lower mean Sexual Satisfaction Scale than the control group.

Conclusions

The results provide evidence for the association between male sex hormone suppression in patients with tramadol dependence with high Addiction Severity Index of tramadol dependence.
Practical concept of traveltime inversion of simulated P-wave vertical seismic profile data in weak to moderate arbitrary anisotropy
Authors: Pšenčík Ivan , Růžek Bohuslav , Jílek Petr
Published: May 2020

We have developed a practical concept of compressional wave (P-wave) traveltime inversion in weakly to moderately anisotropic media of arbitrary symmetry and orientation. The concept provides sufficient freedom to explain and reproduce observed anisotropic seismic signatures to a high degree of accuracy. The key to this concept is the proposed P-wave anisotropy parameterization (A-parameters) that, together with the use of the weak-anisotropy approximation, leads to a significantly simplified theory. Here, as an example, we use a simple and transparent formula relating P-wave traveltimes to 15 P-wave A-parameters describing anisotropy of arbitrary symmetry. The formula is used in the inversion scheme, which does not require any a priori information about anisotropy symmetry and its orientation, and it is applicable to weak and moderate anisotropy. As the first step, we test applicability of the proposed scheme on a blind inversion of synthetic P-wave traveltimes generated in vertical seismic profile experiments in homogeneous models. Three models of varying anisotropy are used: tilted orthorhombic and triclinic models of moderate anisotropy (approximately 10%) and an orthorhombic model of strong anisotropy (>25%) with a horizontal plane of symmetry. In all cases, the inversion yields the complete set of 15 P-wave A-parameters, which make reconstruction of corresponding phase-velocity surfaces possible with high accuracy. The inversion scheme is robust with respect to noise and the source distribution pattern. Its quality depends on the angular illumination of the medium; we determine how the absence of nearly horizontal propagation directions affects inversion accuracy. The results of the inversion are applicable, for example, in migration or as a starting model for inversion methods, such as full-waveform inversion, if a model refinement is desired. A similar procedure could be designed for the inversion of S-wave traveltimes in anisotropic media of arbitrary symmetry.
Multi-parameter wavefield reconstruction inversion for wavespeed and attenuation with bound constraints and total variation regularization
Authors: Aghamiry Hossein S. , Gholami Ali , Operto Stéphane
Published: May 2020

Wavefield reconstruction inversion (WRI) extends the search space of Full Waveform Inversion (FWI) by allowing for wave equation errors during wavefield reconstruction to match the data from the first iteration. Then, the wavespeeds are updated from the wavefields by minimizing the source residuals. Performing these two tasks in alternating mode breaks down the nonlinear FWI as a sequence of two linear subproblems, relaying on the bilinearity of the wave equation. We solve this biconvex optimization with the alternating-direction method of multipliers (ADMM) to cancel out efficiently the data and source residuals in iterations and stabilize the parameter estimation with appropriate regularizations.Here, we extend WRI to viscoacoustic media for attenuation imaging. Attenuation reconstruction is challenging because of the small imprint of attenuation in the data and the crosstalks with velocities. To address these issues, we recast the multivariate viscoacoustic WRI as a triconvex optimization and update wavefields, squared slowness, and attenuation factor in alternating mode at each WRI iteration. This requires to linearize the attenuation-estimation subproblem via an approximated trilinear viscoacoustic wave equation. The iterative defect correction embedded in ADMM corrects the errors generated by this linearization, while the operator splitting allows us to tailor ℓ1 regularization to each parameter class. A toy numerical example shows that these strategies mitigate crosstalk artifacts and noise from the attenuation reconstruction. A more realistic example representative of the North sea further shows the ability of the method to jointly reconstruct the wavespeed and the attenuation starting from a very crude attenuation-free initial model, the moderate strength of the crosstalk artifacts and the sensitivity of the multi-parameter reconstruction to noise.
Schwann cell reprogramming into repair cells increases miRNA-21 expression in exosomes promoting axonal growth
Authors: López-Leal Rodrigo , Díaz-Viraqué Florencia , Catalán Romina J. , Saquel Cristian , Enright Anton , Iraola Gregorio , Court Felipe A.
Published: May 2020

Functional recovery after peripheral nerve damage is dependent on the reprogramming of differentiated Schwann cells (dSCs) into repair Schwann cells (rSCs), which promotes axonal regeneration and tissue homeostasis. Transition into a repair phenotype requires expression of c-Jun and Sox2, which transcriptionally mediates inhibition of the dSC program of myelination and activates a non-cell-autonomous repair program, characterized by the secretion of neuronal survival and regenerative molecules, formation of a cellular scaffold to guide regenerating axons and activation of an innate immune response. Moreover, rSCs release exosomes that are internalized by peripheral neurons, promoting axonal regeneration. Here, we demonstrate that reprogramming of Schwann cells (SCs) is accompanied by a shift in the capacity of their secreted exosomes to promote neurite growth, which is dependent on the expression of c-Jun (also known as Jun) and Sox2 by rSCs. Furthermore, increased expression of miRNA-21 is responsible for the pro-regenerative capacity of rSC exosomes, which is associated with PTEN downregulation and PI3-kinase activation in neurons. We propose that modification of exosomal cargo constitutes another important feature of the repair program of SCs, contributing to axonal regeneration and functional recovery after nerve injury.
Naturally occurring and tumor-associated variants of RNF167 promote lysosomal exocytosis and plasma membrane resealing
Authors: Nair Sreeja V. , Narendradev Nikhil Dev , Nambiar Rithwik P. , Kumar Rakesh , Srinivasula Srinivasa M.
Published: May 2020

Lysosomal exocytosis and resealing of damaged plasma membrane are essential for cellular homeostasis and tumor invasion. However, very little is known of the molecular machinery that regulates these physiological processes. Moreover, no mutations in any of the known regulators of lysosomal exocytosis in primary tumors of patients have been characterized. Here we demonstrate that RNF167-a, a lysosomal-associated ubiquitin ligase, negatively regulates lysosomal exocytosis by inducing perinuclear clustering of lysosomes. Importantly, we also characterized a set of novel natural mutations in RNF167-a, which are commonly found in diverse tumor types. We found that RNF167-a-K97N mutant, unlike the wild type, localizes in the cytoplasm and does not promote perinuclear lysosomal clustering. Furthermore, cells expressing RNF167-a-K97N exhibit dispersed lysosomes, increased exocytosis and enhanced plasma membrane repair. Interestingly, these functional features of RNF167-a-K97N were shared with a naturally occurring short version of RNF167 (isoform RNF167-b). In brief, the results presented here reveal a novel role of RNF167-a, as well as its natural variants RNF167-a-K97N and RNF167-b, as an upstream regulator of lysosomal exocytosis and plasma membrane resealing.
Sensitive detection of protein ubiquitylation using a protein fragment complementation assay
Authors: Le Boulch Marie , Brossard Audrey , Le Dez Gaëlle , Léon Sébastien , Rabut Gwenaël
Published: May 2020

Ubiquitylation is a reversible post-translational protein modification that regulates a multitude of cellular processes. Detection of ubiquitylated proteins is often challenging because of their low abundance. Here, we present NUbiCA, a sensitive protein-fragment complementation assay to facilitate the monitoring of ubiquitylation events in cultured cells and model organisms. Using yeast as a model system, we demonstrate that NUbiCA enables accurate monitoring of mono- and polyubiquitylation of proteins expressed at endogenous levels. We also show that it can be applied to decipher the topology of ubiquitin conjugates. Moreover, we assembled a genome-wide collection of yeast strains ready to investigate the ubiquitylation of proteins with this new assay. This resource will facilitate the analysis of local or transient ubiquitylation events that are difficult to detect with current methods.
Laminin-511 and α6 integrins regulate the expression of CXCR4 to promote endothelial morphogenesis
Authors: Xu Hao , Pumiglia Kevin , LaFlamme Susan E.
Published: May 2020

During angiogenesis, endothelial cells engage components of the extracellular matrix through integrin-mediated adhesion. Endothelial expression of laminin-411 and laminin-511 is known to promote vessel stability. However, little is known about the contribution of these laminins to endothelial morphogenesis. We used two organotypic cell culture angiogenesis assays, in conjunction with RNAi approaches, to demonstrate that depletion of either the α4 chain of laminin-411 (LAMA4) or the α5 chain of laminin-511 (LAMA5) from endothelial cells inhibits sprouting and tube formation. Depletion of α6 (ITGA6) integrins resulted in similar phenotypes. Gene expression analysis indicated that loss of either laminin-511 or α6 integrins inhibited the expression of CXCR4, a gene previously associated with angiogenic endothelial cells. Pharmacological or RNAi-dependent inhibition of CXCR4 suppressed endothelial sprouting and morphogenesis. Importantly, expression of recombinant CXCR4 rescued endothelial morphogenesis when α6 integrin expression was inhibited. Additionally, the depletion of α6 integrins from established tubes resulted in the loss of tube integrity and laminin-511. Taken together, our results indicate that α6 integrins and laminin-511 can promote endothelial morphogenesis by regulating the expression of CXCR4 and suggest that the α6-dependent deposition of laminin-511 protects the integrity of established endothelial tubes.
A simple device to immobilize protists for electrophysiology and microinjection
Authors: Kulkarni Anirudh , Elices Irene , Escoubet Nicolas , Pontani Léa-Laetitia , Prevost Alexis Michel , Brette Romain
Published: May 2020

We present a simple device to mechanically immobilize motile cells such as ciliates. It can be used in particular for intracellular electrophysiology and microinjection. A transparent filter with holes smaller than the specimen is stretched over an outlet. A flow is induced by either a peristaltic pump or a depressurized tank, mechanically entraining cells to the bottom, where they are immobilized against the filter. The cells start swimming again as soon as the flow is stopped. We demonstrate the device by recording action potentials in Paramecium and injecting a fluorescent dye into the cytosol.
Hydroxyapatite Formation from Octacalcium Phosphate and Its Related Compounds: A Discussion of the Transformation Mechanism
Authors: Yokoi Taishi , Goto Tomoyo , Kato Takeharu , Takahashi Seiji , Nakamura Jin , Sekino Tohru , Ohtsuki Chikara , Kawashita Masakazu
Published: May 2020

Octacalcium phosphate (OCP), which has a layered structure composed of an apatitic layer and a hydrated layer, is a precursor of hydroxyapatite (HAp). Although the topotactic transformation of OCP to HAp is a well-known phenomenon, its mechanism remains unclear. In this study, to clarify the role of the OCP hydrated layer in the mentioned transformation, we investigated the behavior of the transformation of OCP with hydrated layers of different thicknesses to HAp under hydrothermal conditions. We used three types of samples: plain OCP (Pure-OCP), OCP with incorporated succinate ions (Suc-OCP), and OCP with incorporated suberate ions (Sub-OCP). We found that all three OCP types transformed topotactically into HAp. The order of reactivity was Sub-OCP > Suc-OCP > Pure-OCP, which corresponds to the thickness of the hydrated layer. Since the transformation involves a compositional change, our finding implies that the hydrated layer acts as a diffusion (mass transfer) passage for dicarboxylate ions and hydrogen phosphate ions located within it, which move outside the crystal during the topotactic transformation. Our results thus contribute to a better understanding of the topotactic transformation mechanism of OCPs to HAp.