bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep intronic deletion in intron 3 of PLP1 is associated with a severe phenotype of Pelizaeus-Merzbacher disease
Authors: Yamamoto-Shimojima Keiko , Akagawa Hiroyuki , Yanagi Kumiko , Kaname Tadashi , Okamoto Nobuhiko , Yamamoto Toshiyuki 
Published: April 2021

AbstractRecently, altered PLP1 splicing was confirmed as a genetic cause of hypomyelination of early myelinating structures (HEMS). A novel deep intronic deletion in intron 3 of PLP1 (NM_000533.5: c.453+59_+259del) was identified, and an in vitro minigene assay detected abnormal splicing patterns. However, the clinical and radiological findings of the patient were compatible with a severe phenotype of Pelizaeus-Merzbacher disease rather than HEMS, which may be due to undetected abnormal PLP1 splicing.
A cross-species analysis of systemic mediators of repair and complex tissue regeneration
Authors: Losner Julia , Courtemanche Katharine , Whited Jessica L. 
Published: April 2021

AbstractRegeneration is an elegant and complex process informed by both local and long-range signals. Many current studies on regeneration are largely limited to investigations of local modulators within a canonical cohort of model organisms. Enhanced genetic tools increasingly enable precise temporal and spatial perturbations within these model regenerators, and these have primarily been applied to cells within the local injury site. Meanwhile, many aspects of broader spatial regulators of regeneration have not yet been examined with the same level of scrutiny. Recent studies have shed important insight into the significant effects of environmental cues and circulating factors on the regenerative process. These observations highlight that consideration of more systemic and possibly more broadly acting cues will also be critical to fully understand complex tissue regeneration. In this review, we explore the ways in which systemic cues and circulating factors affect the initiation of regeneration, the regenerative process, and its outcome. As this is a broad topic, we conceptually divide the factors based on their initial input as either external cues (for example, starvation and light/dark cycle) or internal cues (for example, hormones); however, all of these inputs ultimately lead to internal responses. We consider studies performed in a diverse set of organisms, including vertebrates and invertebrates. Through analysis of systemic mediators of regeneration, we argue that increased investigation of these “systemic factors” could reveal novel insights that may pave the way for a diverse set of therapeutic avenues.
Differential effects of changes in cardiorespiratory fitness on worst- and best- school subjects
Authors: Ishihara Toru , Morita Noriteru , Nakajima Toshihiro , Yamatsu Koji , Okita Koichi , Sagawa Masato , Kamijo Keita 
Published: April 2021

AbstractAccumulating evidence shows a beneficial association between physical fitness and school children’s academic performance. However, several other studies have failed to demonstrate such an association. We reanalyzed data of a two-year longitudinal study of the association between changes in cardiorespiratory fitness and academic performance of school children by focusing on intra-individual variability in grade points as a possible source of this discrepancy. We analyzed data from 469 junior high school students to examine if improvements in cardiorespiratory fitness had a differential effect on an individual student’s worst and best grade points. Results indicated that improvements in physical fitness were associated with an improvement in the worst grade points. On the contrary, we did not observe a similar longitudinal association with the best grade points. These findings suggest that improving cardiorespiratory fitness improves the worst grade points of an individual, selectively. We suggest that intra-individual variability in grade points might moderate the association between physical fitness and academic performance changes.
A VLP for validation of the Plasmodium falciparum circumsporozoite protein junctional epitope for vaccine development
Authors: Atcheson Erwan , Hill Adrian V. S. , Reyes-Sandoval Arturo 
Published: April 2021

AbstractMalaria continues to be a pressing global health issue, causing nearly half a million deaths per year. An effective malaria vaccine could radically improve our ability to control and eliminate this pathogen. The most advanced malaria vaccine, RTS,S, confers only 30% protective efficacy under field conditions, and hence the search continues for improved vaccines. New antigens and formulations are always first developed at a pre-clinical level. This paper describes the development of a platform to supplement existing tools of pre-clinical malaria vaccine development, by displaying linear peptides on a virus-like particle (VLP). Peptides from PfCSP, particularly from outside the normal target of neutralizing antibodies, the central NANP repeat region, are screened for evidence of protective efficacy. One peptide, recently identified as a target of potent neutralizing antibodies and lying at the junction between the N-terminal domain and the central repeat region of PfCSP, is found to confer protective efficacy against malaria sporozoite challenge in mice when presented on the Qβ VLP. The platform is also used to explore the effects of increasing numbers of NANP unit repeats, and including a universal CD4+T-cell epitope from tetanus toxin, on immunogenicity and protective efficacy. The VLP-peptide platform is shown to be of use in screening malaria peptides for protective efficacy and answering basic vaccinology questions in a pre-clinical setting.
Photophysics of DFHBI bound to RNA aptamer Baby Spinach
Authors: Dao Nguyen Thuan , Haselsberger Reinhard , Khuc Mai Thu , Phan Anh Tuân , Voityuk Alexander A. , Michel-Beyerle Maria-Elisabeth 
Published: April 2021

AbstractThe discovery of the GFP-type dye DFHBI that becomes fluorescent upon binding to an RNA aptamer, termed Spinach, led to the development of a variety of fluorogenic RNA systems that enable genetic encoding of living cells. In view of increasing interest in small RNA aptamers and the scarcity of their photophysical characterisation, this paper is a model study on Baby Spinach, a truncated Spinach aptamer with half its sequence. Fluorescence and fluorescence excitation spectra of DFHBI complexes of Spinach and Baby Spinach are known to be similar. Surprisingly, a significant divergence between absorption and fluorescence excitation spectra of the DFHBI/RNA complex was observed on conditions of saturation at large excess of RNA over DFHBI. Since absorption spectra were not reported for any Spinach-type aptamer, this effect is new. Quantitative modelling of the absorption spectrum based on competing dark and fluorescent binding sites could explain it. However, following reasoning of fluorescence lifetimes of bound DFHBI, femtosecond-fluorescence lifetime profiles would be more supportive of the notion that the abnormal absorption spectrum is largely caused by trans-isomers formed within the cis-bound DFHBI/RNA complex. Independent of the origin, the unexpected discrepancy between absorption and fluorescence excitation spectra allows for easily accessed screening and insight into the efficiency of a fluorogenic dye/RNA system.
A wearable light-touch contact device for human balance support
Authors: Shima Keisuke , Shimatani Koji , Sakata Mami 
Published: April 2021

AbstractThere is an urgent need for the development of ways to address the major issue of falls among today’s globally aging population. The authors here outline a new approach referred to as virtual light-touch contact to mitigate postural sway during ambulatory and stationary periods, and propose a wearable light-touch (WLT) system featuring a virtual partition around the user that allows determination of virtual forces resulting from related contact. The data produced are used to create vibrotactile fingertip feedback, which supports comprehensive perception of the partition. Non-impaired subjects were recruited to support evaluation of the prototype system (incorporating tactile stimulation and motion-capture technology), with outcomes showing successful mitigation of postural sway in a heel-to-toe tandem stance. Research performed with 150 able-bodied volunteers to validate the performance of the new set-up (incorporating an acceleration sensor and a voice coil motor to render the light-touch effect) suggested that the proposed WLT approach supports human balance on a level comparable to that of the light-touch effect.
The virome of German bats: comparing virus discovery approaches
Authors: Kohl Claudia , Brinkmann Annika , Radonić Aleksandar , Dabrowski Piotr Wojtek , Mühldorfer Kristin , Nitsche Andreas , Wibbelt Gudrun , Kurth Andreas 
Published: April 2021

AbstractBats are known to be reservoirs of several highly pathogenic viruses. Hence, the interest in bat virus discovery has been increasing rapidly over the last decade. So far, most studies have focused on a single type of virus detection method, either PCR, virus isolation or virome sequencing. Here we present a comprehensive approach in virus discovery, using all three discovery methods on samples from the same bats. By family-specific PCR screening we found sequences of paramyxoviruses, adenoviruses, herpesviruses and one coronavirus. By cell culture we isolated a novel bat adenovirus and bat orthoreovirus. Virome sequencing revealed viral sequences of ten different virus families and orders: three bat nairoviruses, three phenuiviruses, one orbivirus, one rotavirus, one orthoreovirus, one mononegavirus, five parvoviruses, seven picornaviruses, three retroviruses, one totivirus and two thymoviruses were discovered. Of all viruses identified by family-specific PCR in the original samples, none was found by metagenomic sequencing. Vice versa, none of the viruses found by the metagenomic virome approach was detected by family-specific PCRs targeting the same family. The discrepancy of detected viruses by different detection approaches suggests that a combined approach using different detection methods is necessary for virus discovery studies.
Ascorbate oxidation by iron, copper and reactive oxygen species: review, model development, and derivation of key rate constants
Authors: Shen Jiaqi , Griffiths Paul T. , Campbell Steven J. , Utinger Battist , Kalberer Markus , Paulson Suzanne E. 
Published: April 2021

AbstractAscorbic acid is among the most abundant antioxidants in the lung, where it likely plays a key role in the mechanism by which particulate air pollution initiates a biological response. Because ascorbic acid is a highly redox active species, it engages in a far more complex web of reactions than a typical organic molecule, reacting with oxidants such as the hydroxyl radical as well as redox-active transition metals such as iron and copper. The literature provides a solid outline for this chemistry, but there are large disagreements about mechanisms, stoichiometries and reaction rates, particularly for the transition metal reactions. Here we synthesize the literature, develop a chemical kinetics model, and use seven sets of laboratory measurements to constrain mechanisms for the iron and copper reactions and derive key rate constants. We find that micromolar concentrations of iron(III) and copper(II) are more important sinks for ascorbic acid (both AH2and AH−) than reactive oxygen species. The iron and copper reactions are catalytic rather than redox reactions, and have unit stoichiometries: Fe(III)/Cu(II) + AH2/AH− + O2→ Fe(III)/Cu(II) + H2O2 + products. Rate constants are 5.7 × 104and 4.7 × 104 M−2 s−1for Fe(III) + AH2/AH−and 7.7 × 104and 2.8 × 106 M−2 s−1for Cu(II) + AH2/AH−, respectively.
Systemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generation
Authors: Fontelles Camile C. , da Cruz Raquel Santana , Gonsiewski Alexandra K. , Barin Ersilia , Tekmen Volkan , Jin Lu , Cruz M. Idalia , Loudig Olivier , Warri Anni , de Assis Sonia 
Published: April 2021

AbstractWe previously showed that environmentally-induced epigenetic inheritance of cancer occurs in rodent models. For instance, we reported that paternal consumption of an obesity-inducing diet (OID) increased breast cancer susceptibility in the offspring (F1). Nevertheless, it is still unclear whether programming of breast cancer in daughters is due to systemic alterations or mammary epithelium-specific factors and whether the breast cancer predisposition in F1 progeny can be transmitted to subsequent generations. In this study, we show that mammary glands from F1 control (CO) female offspring exhibit enhanced growth when transplanted into OID females compared to CO mammary glands transplanted into CO females. Similarly, carcinogen-induced mammary tumors from F1 CO female offspring transplanted into OID females has a higher proliferation/apoptosis rate. Further, we show that granddaughters (F2) from the OID grand-paternal germline have accelerated tumor growth compared to CO granddaughters. This between-generation transmission of cancer predisposition is associated with changes in sperm tRNA fragments in OID males. Our findings indicate that systemic and mammary stromal alterations are significant contributors to programming of mammary development and likely cancer predisposition in OID daughters. Our data also show that breast cancer predisposition is transmitted to subsequent generations and may explain some familial cancers, if confirmed in humans.
Reliability of urinary charged metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry
Authors: Ishibashi Yoshiki , Harada Sei , Takeuchi Ayano , Iida Miho , Kurihara Ayako , Kato Suzuka , Kuwabara Kazuyo , Hirata Aya , Shibuki Takuma , Okamura Tomonori , Sugiyama Daisuke , Sato Asako , Amano Kaori , Hirayama Akiyoshi , Sugimoto Masahiro , Soga Tomoyoshi , Tomita Masaru , Takebayashi Toru 
Published: April 2021

AbstractCurrently, large-scale cohort studies for metabolome analysis have been launched globally. However, only a few studies have evaluated the reliability of urinary metabolome analysis. This study aimed to establish the reliability of urinary metabolomic profiling in cohort studies. In the Tsuruoka Metabolomics Cohort Study, 123 charged metabolites were identified and routinely quantified using capillary electrophoresis-mass spectrometry (CE-MS). We evaluated approximately 750 quality control (QC) samples and 6,720 participants’ spot urine samples. We calculated inter- and intra-batch coefficients of variation in the QC and participant samples and technical intraclass correlation coefficients (ICC). A correlation of metabolite concentrations between spot and 24-h urine samples obtained from 32 sub-cohort participants was also evaluated. The coefficient of variation (CV) was less than 20% for 87 metabolites (70.7%) and 20–30% for 19 metabolites (15.4%) in the QC samples. There was less than 20% inter-batch CV for 106 metabolites (86.2%). Most urinary metabolites would have reliability for measurement. The 96 metabolites (78.0%) was above 0.75 for the estimated ICC, and those might be useful for epidemiological analysis. Among individuals, the Pearson correlation coefficient of 24-h and spot urine was more than 70% for 59 of the 99 metabolites. These results show that the profiling of charged metabolites using CE-MS in morning spot human urine is suitable for epidemiological metabolomics studies.
Accuracy of theoretical IOL formulas for Panoptix intraocular lens according to axial length
Authors: Choi Ayoung , Kwon Hyunggoo , Jeon Sohee 
Published: April 2021

AbstractThe accuracy of intraocular lens (IOL) calculations is suboptimal for long or short eyes, which results in a low visual quality after multifocal IOL implantation. The purpose of the present study is to evaluate the accuracy of IOL formulas (Barrett Universal II, SRK/T, Holladay 1, Hoffer Q, and Haigis) for the Acrysof IQ Panoptix TFNT IOL (Alcon Laboratories, Inc, Fort Worth, Texas, United States) implantation based on the axial length (AXL) from a large cohort of 2018 cases and identify the factors that are associated with a high mean absolute error (MAE). The Barrett Universal II showed the lowest MAE in the normal AXL group (0.30 ± 0.23), whereas the Holladay 1 and Hoffer Q showed the lowest MAE in the short AXL group (0.32 ± 0.22 D and 0.32 ± 0.21 D, respectively). The Haigis showed the lowest MAE in the long AXL group (0.24 ± 0.19 D). The Barrett Universal II did not perform well in short AXL eyes with higher astigmatism (P = 0.013), wider white-to-white (WTW; P < 0.001), and shorter AXL (P = 0.016). Study results suggest that the Barrett Universal II performed best for the TFNT IOL in the overall study population, except for the eyes with short AXL, particularly when the eyes had higher astigmatism, wider WTW, and shorter AXL.
Transverse aortic constriction induces gut barrier alterations, microbiota remodeling and systemic inflammation
Authors: Boccella Nicola , Paolillo Roberta , Coretti Lorena , D’Apice Stefania , Lama Adriano , Giugliano Giuseppe , Schiattarella Gabriele Giacomo , Cuomo Mariella , d’Aquino Ilaria , Cavaliere Gina , Paciello Orlando , Mollica Maria Pina , Mattace Raso Giuseppina , Esposito Giovanni , Lembo Francesca , Perrino Cinzia 
Published: April 2021

AbstractAccumulating evidence suggests that modifications of gut function and microbiota composition might play a pivotal role in the pathophysiology of several cardiovascular diseases, including heart failure (HF). In this study we systematically analysed gut microbiota composition, intestinal barrier integrity, intestinal and serum cytokines and serum endotoxin levels in C57BL/6 mice undergoing pressure overload by transverse aortic constriction (TAC) for 1 and 4 weeks. Compared to sham-operated animals, TAC induced prompt and strong weakening of intestinal barrier integrity, long-lasting decrease of colon anti-inflammatory cytokine levels, significant increases of serum levels of bacterial lipopolysaccharide and proinflammatory cytokines. TAC also exerted effects on microbiota composition, inducing significant differences in bacterial genera inside Actinobacteria, Firmicutes, Proteobacteria and TM7 phyla as shown by 16S rDNA sequencing of fecal samples from TAC or sham mice. These results suggest that gut modifications represent an important element to be considered in the development and progression of cardiac dysfunction in response to TAC and support this animal model as a valuable tool to establish the role and mechanisms of gut-heart crosstalk in HF. Evidence arising in this field might identify new treatment options targeting gut integrity and microbiota components to face adverse cardiac events.
Toward the discovery of biological functions associated with the mechanosensor Mtl1p of Saccharomyces cerevisiae via integrative multi-OMICs analysis
Authors: Martínez-Matías Nelson , Chorna Nataliya , González-Crespo Sahily , Villanueva Lilliam , Montes-Rodríguez Ingrid , Melendez-Aponte Loyda M. , Roche-Lima Abiel , Carrasquillo-Carrión Kelvin , Santiago-Cartagena Ednalise , Rymond Brian C. , Babu Mohan , Stagljar Igor , Rodríguez-Medina José R. 
Published: April 2021

AbstractFunctional analysis of the Mtl1 protein in Saccharomyces cerevisiae has revealed that this transmembrane sensor endows yeast cells with resistance to oxidative stress through a signaling mechanism called the cell wall integrity pathway (CWI). We observed upregulation of multiple heat shock proteins (HSPs), proteins associated with the formation of stress granules, and the phosphatase subunit of trehalose 6-phosphate synthase which suggests that mtl1Δ strains undergo intrinsic activation of a non-lethal heat stress response. Furthermore, quantitative global proteomic analysis conducted on TMT-labeled proteins combined with metabolome analysis revealed that mtl1Δ strains exhibit decreased levels of metabolites of carboxylic acid metabolism, decreased expression of anabolic enzymes and increased expression of catabolic enzymes involved in the metabolism of amino acids, with enhanced expression of mitochondrial respirasome proteins. These observations support the idea that Mtl1 protein controls the suppression of a non-lethal heat stress response under normal conditions while it plays an important role in metabolic regulatory mechanisms linked to TORC1 signaling that are required to maintain cellular homeostasis and optimal mitochondrial function.
PaO2/FiO2 and IL-6 are risk factors of mortality for intensive care COVID-19 patients
Authors: Gu Yanli , Wang Donghui , Chen Cen , Lu Wanjun , Liu Hongbing , Lv Tangfeng , Song Yong , Zhang Fang 
Published: April 2021

AbstractTo identify the risk factors of mortality for the coronavirus disease 19 (COVID-19) patients admitted to intensive care units (ICUs) through a retrospective analysis. The demographic, clinical, laboratory, and chest imaging data of patients admitted to the ICU of Huoshenshan Hospital from February 10 to April 10, 2020 were retrospectively analyzed. Student's t-test and Chi-square test were used to compare the continuous and categorical variables, respectively. The logistic regression model was employed to ascertain the risk factors of mortality. This retrospective study involved 123 patients, including 64 dead and 59 survivors. Among them, 57 people were tested for interleukin-6 (IL-6) (20 died and 37 survived). In all included patients, the oxygenation index (PaO2/FiO2) was identified as an independent risk factor (odd ratio [OR] = 0.96, 95% confidence interval [CI]: 0.928–0.994, p = 0.021). The area under the curve (AUC) was 0.895 (95% CI: 0.826–0.943, p < 0.0001). Among the patients tested for IL-6, the PaO2/FiO2 (OR = 0.955, 95%CI: 0.915–0.996, p = 0.032) and IL-6 (OR = 1.013, 95%CI: 1.001–1.025, p = 0.028) were identified as independent risk factors. The AUC was 0.9 (95% CI: 0.791–0.964, p < 0.0001) for IL-6 and 0.865 (95% CI: 0.748–0.941, p < 0.0001) for PaO2/FiO2. PaO2/FiO2 and IL-6 could potentially serve as independent risk factors for predicting death in COVID-19 patients requiring intensive care.
Effects of pyrolysis temperature, feedstock type and compaction on water retention of biochar amended soil
Authors: Huang He , Reddy Narala Gangadhara , Huang Xilong , Chen Peinan , Wang Peiying , Zhang Yuantian , Huang Yuanxu , Lin Peng , Garg Ankit 
Published: April 2021

AbstractRecent studies on water retention behaviour of biochar amended soil rarely considers the effect of pyrolysis temperature and also feedstock type into account. It is well known that pyrolysis temperature and feedstock type influences the physical and chemical properties of biochar due to stagewise decomposition of structure and chemical bonds. Further, soil density, which is in a loose state (in agricultural applications) and dense (in geo-environmental engineering applications) can also influence water retention behaviour of biochar amended soils. The major objective of this study is to investigate the water retention properties of soil amended with three different biochars in both loose and dense state. The biochars, i.e. water hyacinth biochar (WHB), chicken manure biochar (CMB) and wood biochar (WB) were produced in-house at different pyrolysis temperature. After then, biochars at 5% and 10% (w/w%) were amended to the soil. Water retention behaviour (soil suction and gravimetric water content) was studied under drying and wetting cycle simulated by varying relative humidity (RH, 50–90%). Results show that 10% WHB produced at 300 °C were found to possess highest water retention. CMB is found to possess higher water retention than WB for 10% amendment ratio. In general, the addition of three biochars (at both 300 °C and 600 °C) at 10% (w/w) significantly improved the water retention at all suction ranges in both loose and dense compaction state as compared to that of the bare soil. The adsorption (wetting) and desorption (drying) capacity of biochar amended soils is constant at corresponding RH.