bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synaptotagmin 7 switches short-term synaptic plasticity from depression to facilitation by suppressing synaptic transmission
Authors: Fujii Takaaki , Sakurai Akira , Littleton J. Troy , Yoshihara Motojiro 
Published: February 2021

AbstractShort-term synaptic plasticity is a fast and robust modification in neuronal presynaptic output that can enhance release strength to drive facilitation or diminish it to promote depression. The mechanisms that determine whether neurons display short-term facilitation or depression are still unclear. Here we show that the Ca2+-binding protein Synaptotagmin 7 (Syt7) determines the sign of short-term synaptic plasticity by controlling the initial probability of synaptic vesicle (SV) fusion. Electrophysiological analysis of Syt7 null mutants at Drosophila embryonic neuromuscular junctions demonstrate loss of the protein converts the normally observed synaptic facilitation response during repetitive stimulation into synaptic depression. In contrast, overexpression of Syt7 dramatically enhanced the magnitude of short-term facilitation. These changes in short-term plasticity were mirrored by corresponding alterations in the initial evoked response, with SV release probability enhanced in Syt7 mutants and suppressed following Syt7 overexpression. Indeed, Syt7 mutants were able to display facilitation in lower [Ca2+] where release was reduced. These data suggest Syt7 does not act by directly sensing residual Ca2+ and argues for the existence of a distinct Ca2+ sensor beyond Syt7 that mediates facilitation. Instead, Syt7 normally suppresses synaptic transmission to maintain an output range where facilitation is available to the neuron.
Composite cardiovascular risk and BMI affected comparative profiles of BIAsp 30 + metformin vs BIAsp 30 monotherapy: a MERIT post-hoc analysis
Authors: Guo Lixin , Chang Baocheng , Chen Li , Yang Liyong , Liu Yu , Feng Bo , He Qinghua 
Published: February 2021

AbstractWe assessed whether comparative efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) plus metformin versus BIAsp 30 monotherapy differed for patients with type 2 diabetes mellitus (T2DM) inadequately controlled with oral antidiabetic drugs with different cardiovascular risk scores and different body mass indexes (BMI) by performing a post hoc analysis of the randomized controlled MERIT study. In the MERIT study, eligible patients were randomized 1:1 to receive BIAsp 30 plus metformin or BIAsp 30 for 16 weeks. Patients in the 2 treatment groups were classified into “low” and “high” risk subgroups based on their GloboRisk scores and into “BMI ≤ 26 kg/m2”and “BMI > 26 kg/m2” subgroups. Primary efficacy endpoint was between-treatments comparison of HbA1c changes from baseline for these 2 sets of subgroups. Between-treatments comparisons of secondary efficacy and safety endpoints were also performed. We found that BIAsp 30 plus metformin led to significantly higher percentage of high-risk patients achieving HbA1c target < 7% than BIAsp 30 monotherapy, with an overall comparable safety profile for high-risk patients. Meanwhile, for patients with BMI ≤ 26 kg/m2, compared with BIAsp 30 monotherapy, BIAsp 30 plus metformin led to significantly higher percentages of patients achieving HbA1c target (47.83% vs 28.17%, P = 0.0165) and composite target of HbA1c < 7% without hypoglycemia or weight gain (20.29% vs 6.85%, P = 0.0187) and have a slightly better safety profile. In conclusion, for T2DM patients at high CV risk or with BMI ≤ 26 kg/m2, BIAsp 30 plus metformin was preferable to BIAsp 30 monotherapy.
The pressure-enhanced superconducting phase of Sr$$_x$$–Bi$$_2$$Se$$_3$$ probed by hard point contact spectroscopy
Authors: Kumar Ritesh , Vasdev Aastha , Das Shekhar , Howlader Sandeep , Jat Karn S. , Neha Prakriti , Patnaik Satyabrata , Sheet Goutam 
Published: February 2021

AbstractThe superconducting systems emerging from topological insulators upon metal ion intercalation or application of high pressure are ideal for investigation of possible topological superconductivity. In this context, Sr-intercalated Bi$$_2$$

2

Se$$_3$$

3

is specially interesting because it displays pressure induced re-entrant superconductivity where the high pressure phase shows almost two times higher $$T_c$$

T
c

than the ambient superconducting phase ( $$T_C\sim 2.9$$

T
C

∼
2.9

K). Interestingly, unlike the ambient phase, the pressure-induced superconducting phase shows strong indication of unconventional superconductivity. However, since the pressure-induced phase remains inaccessible to spectroscopic techniques, the detailed study of the phase remained an unattained goal. Here we show that the high-pressure phase can be realized under a mesoscopic point contact, where transport spectroscopy can be used to probe the spectroscopic properties of the pressure-induced phase. We find that the point contact junctions on the high-pressure phase show unusual response to magnetic field supporting the possibility of unconventional superconductivity.
Herpes simplex virus-1 KOS-63 strain is virulent and causes titer-dependent corneal nerve damage and keratitis
Authors: Moein Hamid-Reza , Sendra Victor G. , Jamali Arsia , Kheirkhah Ahmad , Harris Deshea L. , Hamrah Pedram 
Published: February 2021

AbstractTo investigate the acute clinical, immunological, and corneal nerve changes following corneal HSV-1 KOS-63 strain inoculation. Corneas of C57BL/6 mice were inoculated with either low dose (Ld) or high dose (Hd) HSV-1 KOS-63 or culture medium. Clinical evaluation was conducted up to 7 days post inoculation (dpi). Viral titers were assessed by standard plaque assay. Excised corneas were stained for CD45 and beta-III tubulin. Corneal flow cytometry was performed to assess changes in leukocyte subpopulations. Corneal sensation was measured using a Cochet-Bonnet esthesiometer. Naïve, sham-infected (post scarification), and McKrae-infected C57BL/6 corneas served as two negative and positive controls, respectively. Compared to Ld infected mice, Hd HSV-1 KOS-63 demonstrated higher incidence of corneal opacity (1.5 ×) and neovascularization (2.6 × ; p < 0.05). At 7 dpi Hd infected mice showed more severe corneal opacity (2.23 vs. 0.87; p = 0.0003), neovascularization (6.00 vs. 0.75; p < 0.0001), and blepharitis (3.11 vs. 2.06; p = 0.001) compared to the Ld group. At 3 dpi epitheliopathy was significantly larger in the Hd group (23.59% vs. 3.44%; p = 0.001). Similarly, corneal opacity was significantly higher in Hd McKrae-infected corneas as compared with Ld McKrae-infected corneas at 3 and 5 dpi. No significant corneal opacity, neovascularization, blepharitis, and epitheliopathy were observed in naïve or sham-infected mice. Higher viral titers were detected in corneas (1 and 3 dpi) and trigeminal ganglia (TG) (3 and 5 dpi) in Hd versus Ld KOS-63 groups (p < 0.05). Leukocyte density showed a gradual increase over time from 1 to 7 dpi in both KOS-63 and McKrae-infected corneas. Corneal flow cytometric analysis (3 dpi) demonstrated a higher percentage of Gr-1 + (71.6 vs. 26.3) and CD11b + (90.6 vs. 41.1) cells in Hd versus Ld KOS-63 groups. Corneal nerve density significantly decreased in both Hd KOS-63 and Hd McKrae infected corneas in comparison with naïve and sham-infected corneas. At 3 dpi corneal nerve density was lower in the Hd versus Ld KOS-63 groups (16.79 vs. 57.41 mm/mm2; p = 0.004). Corneal sensation decreased accordingly at 5 and 7 dpi in both Ld and Hd KOS-63-infected mice. Corneal inoculation with HSV-1 KOS-63 strain shows acute keratitis and nerve degeneration in a dose-dependent fashion, demonstrating virulence of this strain.
Flexible brain dynamics underpins complex behaviours as observed in Parkinson’s disease
Authors: Sorrentino Pierpaolo , Rucco Rosaria , Baselice Fabio , De Micco Rosa , Tessitore Alessandro , Hillebrand Arjan , Mandolesi Laura , Breakspear Michael , Gollo Leonardo L. , Sorrentino Giuseppe 
Published: February 2021

AbstractRapid reconfigurations of brain activity support efficient neuronal communication and flexible behaviour. Suboptimal brain dynamics is associated to impaired adaptability, possibly leading to functional deficiencies. We hypothesize that impaired flexibility in brain activity can lead to motor and cognitive symptoms of Parkinson’s disease (PD). To test this hypothesis, we studied the ‘functional repertoire’—the number of distinct configurations of neural activity—using source-reconstructed magnetoencephalography in PD patients and controls. We found stereotyped brain dynamics and reduced flexibility in PD. The intensity of this reduction was proportional to symptoms severity, which can be explained by beta-band hyper-synchronization. Moreover, the basal ganglia were prominently involved in the abnormal patterns of brain activity. Our findings support the hypotheses that: symptoms in PD relate to impaired brain flexibility, this impairment preferentially involves the basal ganglia, and beta-band hypersynchronization is associated with reduced brain flexibility. These findings highlight the importance of extensive functional repertoires for correct behaviour.
Photoacoustic monitoring of oxygenation changes induced by therapeutic ultrasound in murine hepatocellular carcinoma
Authors: Karmacharya Mrigendra B. , Sultan Laith R. , Sehgal Chandra M. 
Published: February 2021

AbstractHepatocellular carcinoma (HCC) is a highly vascular solid tumor. We have previously shown that ultrasound (US) therapy significantly reduces tumor vascularity. This study monitors US-induced changes in tumor oxygenation on murine HCC by photoacoustic imaging (PAI). Oxygen saturation and total hemoglobin were assessed by PAI before and after US treatments performed at different intensities of continuous wave (CW) bursts and pulsed wave (PW) bursts US. PAI revealed significant reduction both in HCC oxygen saturation and in total hemoglobin, proportional to the US intensity. Both CW bursts US (1.6 W/cm2) and the PW bursts US (0.8 W/cm2) significantly reduced HCC oxygen saturation and total hemoglobin which continued to diminish with time following the US treatment. The effects of US therapy were confirmed by power Doppler and histological examination of the hemorrhage in tumors. By each measure, the changes observed in US-treated HCC were more prevalent than those in sham-treated tumors and were statistically significant. In conclusion, the results show that US is an effective vascular-targeting therapy for HCC. The changes in oxygenation induced by the US treatment can be noninvasively monitored longitudinally by PAI without the use of exogenous image-enhancing agents. The combined use of PAI and the therapeutic US has potential for image-guided vascular therapy for HCC.
Quantum semantics of text perception
Authors: Surov Ilya A. , Semenenko E. , Platonov A. V. , Bessmertny I. A. , Galofaro F. , Toffano Z. , Khrennikov A. Yu. , Alodjants A. P. 
Published: February 2021

AbstractThe paper presents quantum model of subjective text perception based on binary cognitive distinctions corresponding to words of natural language. The result of perception is quantum cognitive state represented by vector in the qubit Hilbert space. Complex-valued structure of the quantum state space extends the standard vector-based approach to semantics, allowing to account for subjective dimension of human perception in which the result is constrained, but not fully predetermined by input information. In the case of two distinctions, the perception model generates a two-qubit state, entanglement of which quantifies semantic connection between the corresponding words. This two-distinction perception case is realized in the algorithm for detection and measurement of semantic connectivity between pairs of words. The algorithm is experimentally tested with positive results. The developed approach to cognitive modeling unifies neurophysiological, linguistic, and psychological descriptions in a mathematical and conceptual structure of quantum theory, extending horizons of machine intelligence.
The PHP domain of PolX from Staphylococcus aureus aids high fidelity DNA synthesis through the removal of misincorporated deoxyribo-, ribo- and oxidized nucleotides
Authors: Nagpal Shilpi , Nair Deepak T. 
Published: February 2021

AbstractThe X family is one of the eight families of DNA polymerases (dPols) and members of this family are known to participate in the later stages of Base Excision Repair. Many prokaryotic members of this family possess a Polymerase and Histidinol Phosphatase (PHP) domain at their C-termini. The PHP domain has been shown to possess 3′–5′ exonuclease activity and may represent the proofreading function in these dPols. PolX from Staphylococcus aureus also possesses the PHP domain at the C-terminus, and we show that this domain has an intrinsic Mn2+ dependent 3′–5′ exonuclease capable of removing misincorporated dNMPs from the primer. The misincorporation of oxidized nucleotides such as 8oxodGTP and rNTPs are known to be pro-mutagenic and can lead to genomic instability. Here, we show that the PHP domain aids DNA replication by the removal of misincorporated oxidized nucleotides and rNMPs. Overall, our study shows that the proofreading activity of the PHP domain plays a critical role in maintaining genomic integrity and stability. The exonuclease activity of this enzyme can, therefore, be the target of therapeutic intervention to combat infection by methicillin-resistant-Staphylococcus-aureus.
Genetic analysis and QTL mapping of yield and fruit traits in bitter gourd (Momordica charantia L.)
Authors: Rao P. Gangadhara , Behera T. K. , Gaikwad Ambika B. , Munshi A. D. , Srivastava Arpita , Boopalakrishnan G. , Vinod  
Published: February 2021

AbstractBitter gourd (Momordica charantiaL.) is an economically important vegetable crop grown in tropical parts of the world. In this study, a high-density linkage map ofM. charantiawas constructed through genotyping-by-sequencing (GBS) technology using F2:3mapping population generated from the cross DBGy-201 × Pusa Do Mausami. About 2013 high-quality SNPs were assigned on a total of 20 linkage groups (LGs) spanning over 2329.2 CM with an average genetic distance of 1.16 CM. QTL analysis was performed for six major yield-contributing traits such as fruit length, fruit diameter, fruit weight, fruit flesh thickness, number of fruits per plant and yield per plant. These six quantitative traits were mapped with 19 QTLs (9 QTLs with LOD > 3) using composite interval mapping (CIM). Among 19 QTLs, 12 QTLs derived from ‘Pusa Do Mausami’ revealed a negative additive effect when its allele increased trait score whereas 7 QTLs derived from ‘DBGy-201’ revealed a positive additive effect when its allele trait score increased. The phenotypic variation (R2%) elucidated by these QTLs ranged from 0.09% (fruit flesh thickness) on LG 14 to 32.65% (fruit diameter) on LG 16 and a total of six major QTLs detected. Most QTLs detected in the present study were located relatively very close, maybe due to the high correlation among the traits. This information will serve as a significant basis for marker-assisted selection and molecular breeding in bitter gourd crop improvement.
Relationship between CYP2D6 genotype, activity score and phenotype in a pediatric Thai population treated with risperidone
Authors: Hongkaew Yaowaluck , Gaedigk Andrea , Wilffert Bob , Ngamsamut Nattawat , Kittitharaphan Wiranpat , Limsila Penkhae , Sukasem Chonlaphat 
Published: February 2021

AbstractRecently, the Clinical Pharmacogenetics Implementation Consortium (CPIC) have revised recommendations for the translation of CYP2D6 genotype to phenotype. Changes affect phenotype grouping, as well as the value used to calculate activity score for the CYP2D6*10 allele to better reflect the substantially decreased activity of this allele which is the most frequent allele found in Asian populations. This study aimed to evaluate whether the lower value for CYP2D6*10 as recommended, and the revised phenotype groupings improve the relationship between CYP2D6 genotype and risperidone measures. One hundred and ninety-nine children and adolescents with autism treated with a risperidone-based regimen for at least four weeks were included. CYP2D6 genotype was determined using the Luminex xTAG CYP2D6 Kit assay and translated into phenotype using different translation methods. Plasma concentrations of risperidone and 9-hydroxyrisperidone were measured using LC/MS/MS. Plasma levels of risperidone, risperidone concentration/dose ratio, and risperidone/9-hydroxyrisperidone ratio in patients with an activity score < 1 were significantly higher than those ≥ 1 (P value < 0.001 for all three parameters). Plasma risperidone levels and risperidone concentration/dose ratios were significantly higher in intermediate metabolizers (defined as AS = 0.25–0.75) than normal metabolizer (defined as AS = 1–2) patients (1.44 vs. 0.23 ng/ml, P < 0.001 and 1.63 vs. 0.29 ng/ml/ng, P < 0.001, respectively) as well as risperidone/9-hydroxyrisperidone ratio (0.20 vs. 0.04, P < 0.001). This is the first study in an Asian population utilizing the revised CPIC-recommended method for translating the CYP2D6 genotype to phenotype. In addition to validating that CYP2D6 genetic variation significantly impacts risperidone metabolism, we demonstrated that revised value for the CYP2D6*10 was superior for genotype to phenotype translation. However, at least for risperidone, subjects with an activity score of 1 presented as phenotypic normal, and not intermediate metabolizers, suggesting that phenotype classification is substrate dependent.
Research on crack evolution law and macroscopic failure mode of joint Phyllite under uniaxial compression
Authors: Xu Jiangbo , Fei Dongyang , Yu Yanglin , Cui Yilun , Yan Changgen , Bao Han , Lan Hengxing 
Published: February 2021

AbstractIn order to explore the fracture mechanism of jointed Phyllite, the TAJW-2000 rock mechanics test system is used to carry out uniaxial compression tests on different joint inclination Phyllites. The influence of joint inclination of Phyllite failure mode is discussed, and the progressive failure process of Phyllite is studied. The test results show that the uniaxial compressive strength anisotropy of jointed Phyllite is remarkable. As the inclination increases, it exhibits a U-shaped change; When 30° ≤ α ≤ 75°, the tensile and shear failures along the joint inclination mainly occurs. the joint inclination controls the failure surface form of the Phyllite; The crack initial stress level of the joint Phyllite is 0.30–0.59σf, the crack failure stress level is 0.44–0.86σf. When α = 90°, the σcd value is the largest, and σcd with α = 90° can be used as the maximum reliable value of uniaxial compressive strength of Phyllite. Using the theory of fracture mechanics, it is analyzed that under uniaxial compression of the rock, the crack does not break along the original crack direction, but extends along the direction at a certain angle to the original crack. The joint effect coefficient is proposed to show the influence of the joint inclination on the uniaxial compressive strength of the phyllite. Both the test and simulation results show that when the joint inclination is 60°, the joint effect coefficient is the largest. The compressive strength is the smallest. Numerical simulation analyses the crack evolution law of phyllite under different joint inclination under uniaxial compression, which verifies that there are different failure modes of joint phyllite under uniaxial compression.
Influence of spin finish on degradation, functionalization and long-term storage of polyethylene terephthalate fabrics dedicated to ligament prostheses
Authors: Nguyen Tuan Ngoc , Rangel Andre , Grainger David W. , Migonney Véronique 
Published: February 2021

AbstractPolyethylene terephthalate (PET) fibers and fabrics are widely used for medical device applications such as vascular and anterior cruciate ligament prostheses. Several years ago, we began functionalizing PET fabrics using anionic polymers to enhance their biocompatibility, cell adhesion, proliferation and functional performance as PET ligament prostheses. Polymer functionalization followed a grafting-from process from virgin PET surfaces subject to spin-finish oil additive removal under Soxhlet extraction to remove residual fiber manufacturing oil. Nevertheless, with increasing time from manufacture, PET fabrics stored without a spin finish removal step exhibited degradation of spin finish oil, leading to (1) incomplete surface cleaning, and (2) PET surface degradation. Moreover, oxidizing agents present in the residual degraded oil prevented reliable functionalization of the prosthesis fibers in these PET fabrics. This study compares effects of PET fabric/spin finish oil storage on PET fabric anionic polymer functionalization across two PET fabric ligament storage groups: (1) 2- and 10- year old ligaments, and (2) 26-year old ligaments. Strong interactions between degraded spin finish oil and PET fiber surfaces after long storage times were demonstrated via extraction yield; oil chemistry changed assessed by spectral analysis. Polymer grafting/functionalization efficiency on stored PET fabrics was correlated using atomic force microscopy, including fiber surface roughness and relationships between grafting degree and surface Young’s modulus. New PET fabric Young’s modulus significantly decreased by anionic polymer functionalization (to 96%, grafting degree 1.6 µmol/g) and to reduced modulus and efficiency (29%) for 10 years storage fabric (grafting degree ~ 1 µmol/g). As fiber spin finish is mandatory in biomedically applicable fiber fabrication, assessing effects of spin finish oil on commercial polymer fabrics after longer storage under various conditions (UV light, temperature) is necessary to understand possible impacts on fiber degradation and surface functionalization.
Genome-wide association study identified candidate genes for seed size and seed composition improvement in M. truncatula
Authors: Chen Zhijuan , Lancon-Verdier Vanessa , Le Signor Christine , She Yi-Min , Kang Yun , Verdier Jerome 
Published: February 2021

AbstractGrain legumes are highly valuable plant species, as they produce seeds with high protein content. Increasing seed protein production and improving seed nutritional quality represent an agronomical challenge in order to promote plant protein consumption of a growing population. In this study, we used the genetic diversity, naturally present in Medicago truncatula, a model plant for legumes, to identify genes/loci regulating seed traits. Indeed, using sequencing data of 162 accessions from the Medicago HAPMAP collection, we performed genome-wide association study for 32 seed traits related to seed size and seed composition such as seed protein content/concentration, sulfur content/concentration. Using different GWAS and postGWAS methods, we identified 79 quantitative trait nucleotides (QTNs) as regulating seed size, 41 QTNs for seed composition related to nitrogen (i.e. storage protein) and sulfur (i.e. sulfur-containing amino acid) concentrations/contents. Furthermore, a strong positive correlation between seed size and protein content was revealed within the selected Medicago HAPMAP collection. In addition, several QTNs showed highly significant associations in different seed phenotypes for further functional validation studies, including one near an RNA-Binding Domain protein, which represents a valuable candidate as central regulator determining both seed size and composition. Finally, our findings in M. truncatula represent valuable resources to be exploitable in many legume crop species such as pea, common bean, and soybean due to its high synteny, which enable rapid transfer of these results into breeding programs and eventually help the improvement of legume grain production.