bluuebunny/crossref_metadata_2025 huggingface dataset:
The yeast ISW1b ATP-dependent chromatin remodeler is critical for nucleosome spacing and dinucleosome resolution
Authors: Eriksson Peter R. , Clark David J.
Published: February 2021

Isw1 and Chd1 are ATP-dependent nucleosome-spacing enzymes required to establish regular arrays of phased nucleosomes near transcription start sites of yeast genes. Cells lacking both Isw1 and Chd1 have extremely disrupted chromatin, with weak phasing, irregular spacing and a propensity to form close-packed dinucleosomes. The Isw1 ATPase subunit occurs in two different remodeling complexes: ISW1a (composed of Isw1 and Ioc3) and ISW1b (composed of Isw1, Ioc2 and Ioc4). The Ioc4 subunit of ISW1b binds preferentially to the H3-K36me3 mark. Here we show that ISW1b is primarily responsible for setting nucleosome spacing and resolving close-packed dinucleosomes, whereas ISW1a plays only a minor role. ISW1b and Chd1 make additive contributions to dinucleosome resolution, such that neither enzyme is capable of resolving all dinucleosomes on its own. Loss of the Set2 H3-K36 methyltransferase partly phenocopies loss of Ioc4, resulting in increased dinucleosome levels with only a weak effect on nucleosome spacing, suggesting that Set2-mediated H3-K36 trimethylation contributes to ISW1b-mediated dinucleosome separation. The H4 tail domain is required for normal nucleosome spacing but not for dinucleosome resolution. We conclude that the nucleosome spacing and dinucleosome resolving activities of ISW1b and Chd1 are critical for normal global chromatin organisation.
Causes of death and comorbidities in hospitalized patients with COVID-19
Authors: Elezkurtaj Sefer , Greuel Selina , Ihlow Jana , Michaelis Edward Georg , Bischoff Philip , Kunze Catarina Alisa , Sinn Bruno Valentin , Gerhold Manuela , Hauptmann Kathrin , Ingold-Heppner Barbara , Miller Florian , Herbst Hermann , Corman Victor Max , Martin Hubert , Radbruch Helena , Heppner Frank L. , Horst David
Published: February 2021

Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has been associated with more than two million deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of pre-existing health conditions to death yet is missing, which can be reliably established by autopsy only. We performed full body autopsies on 26 patients that had died after SARS-CoV-2 infection and COVID-19 at the Charité University Hospital Berlin, Germany, or at associated teaching hospitals. We systematically evaluated causes of death and pre-existing health conditions. Additionally, clinical records and death certificates were evaluated. We report findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.
Early protein intake predicts functional connectivity and neurocognition in preterm born children
Authors: Duerden Emma G. , Thompson Benjamin , Poppe Tanya , Alsweiler Jane , Gamble Greg , Jiang Yannan , Leung Myra , Tottman Anna C. , Wouldes Trecia , Miller Steven P. , Harding Jane E. ,   PIANO study group, Alsweiler Jane M. , Biggs Janene B. , Bevan Coila , Black Joanna M. , Bloomfield Frank H. , Fredell Kelly , Gamble Greg D. , Harding Jane E. , Huth Sabine , Jiang Yannan , Kevan Christine , Leung Myra , Phillips Geraint , Poppe Tanya , Rogers Jennifer A. , Stewart Heather , Thompson Benjamin S. , Tottman Anna C. , Williamson Kathryn A. , Wouldes Trecia A.
Published: February 2021

Nutritional intake can promote early neonatal brain development in very preterm born neonates (< 32 weeks’ gestation). In a group of 7-year-old very preterm born children followed since birth, we examined whether early nutrient intake in the first weeks of life would be associated with long-term brain function and neurocognitive skills at school age. Children underwent resting-state functional MRI (fMRI), intelligence testing (Wechsler Intelligence Scale for Children, 5th Ed) and visual-motor processing (Beery-Buktenica, 5th Ed) at 7 years. Relationships were assessed between neonatal macronutrient intakes, functional connectivity strength between thalamic and default mode networks (DMN), and neuro-cognitive function using multivariable regression. Greater functional connectivity strength between thalamic networks and DMN was associated with greater intake of protein in the first week (β = 0.17; 95% CI 0.11, 0.23, p < 0.001) but lower intakes of fat (β = − 0.06; 95% CI − 0.09, − 0.02, p = 0.001) and carbohydrates (β = − 0.03; 95% CI − 0.04, − 0.01, p = 0.003). Connectivity strength was also associated with protein intake during the first month (β = 0.22; 95% CI 0.06, 0.37, p = 0.006). Importantly, greater thalamic-DMN connectivity strength was associated with higher processing speed indices (β = 26.9; 95% CI 4.21, 49.49, p = 0.02) and visual processing scores (β = 9.03; 95% CI 2.27, 15.79, p = 0.009). Optimizing early protein intake may contribute to promoting long-term brain health in preterm-born children.
YBX2 and cancer testis antigen 45 contribute to stemness, chemoresistance and a high degree of malignancy in human endometrial cancer
Authors: Suzuki Izumi , Yoshida Sachiko , Tabu Kouichi , Kusunoki Soshi , Matsumura Yumiko , Izumi Hiroto , Asanoma Kazuo , Yagi Hiroshi , Onoyama Ichiro , Sonoda Kenzo , Kohno Kimitoshi , Taga Tetsuya , Itakura Atsuo , Takeda Satoru , Kato Kiyoko
Published: February 2021

Y-box binding protein 2 (YBX2) has been associated with the properties of both germ cells and cancer cells. We hypothesized that YBX2 might contribute to the characteristics of cancer stem cells (CSCs). In this study, we clarified the function of YBX2 in endometrial cancer stem cells. We established a human YBX2-expressing Ishikawa (IK) cell line (IK-YBX2 cells). We analyzed gene expression associated with stemness and isolated SP cells from IK-YBX2 cells. The SP population of IK-YBX2 cells, the expression ofALDH1and serial sphere-forming capacity were associated with levels of YBX2 expression. IK-YBX2 cells were resistant to anti-cancer drugs. In gene expression analysis, a gene for cancer testis antigen,CT45, was generally overexpressed in IK-YBX2 cells. YBX2-mediated CT45 expression was associated with increased levels of self-renewal capacity and paclitaxel resistance. The level of CT45 expression was enhanced in high-grade and/or advanced stages of human endometrial cancer tissues. We conclude that expression of YBX2 is essential for the stem cell-like phenotype. CT45 contributes to stemness associated with YBX2 and might be related to the progression of endometrial cancer.
Evaluation of the ex vivo liver viability using a nuclear magnetic resonance relaxation time-based assay in a porcine machine perfusion model
Authors: OuYang Qing , Liang Guohai , Tan Xiaoyu , He Xiran , Zhang Lin , Kuang Weijian , Chen Jianxiong , Wang Shaoping , Liang Mingju , Huo Feng
Published: February 2021

There is a dearth of effective parameters for selecting potentially transplantable liver grafts from expanded-criteria donors. In this study, we used a nuclear magnetic resonance (NMR) relaxation analyzer-based assay to assess the viability of ex vivo livers obtained via porcine donation after circulatory death (DCD). Ex situ normothermic machine perfusion (NMP) was utilized as a platform for viability test of porcine DCD donor livers. A liver-targeted contrast agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), was injected into the perfusate during NMP, and the dynamic biliary excretion of the Gd-EOB-DTPA was monitored by measuring the longitudinal relaxation time (T1). The longitudinal relaxation rate (R1) of the bile was served as a parameter. The delay of increase in biliary R1 during early stage of NMP indicated the impaired function of liver grafts in both warm and cold ischemia injury, which was correlated with the change of alanine aminotransferase. The preservative superiority in cold ischemia of dual hypothermic oxygenated machine perfusion could also be verified by assessing biliary R1 and other biochemical parameters. This study allows for the dynamic assessment of the viability of porcine DCD donor livers by combined usage of ex situ NMP and NMR relaxation time based assay, which lays a foundation for further clinical application.
Effect of noisy galvanic vestibular stimulation on dynamic posture sway under visual deprivation in patients with bilateral vestibular hypofunction
Authors: Chen Po-Yin , Jheng Ying-Chun , Wang Chien-Chih , Huang Shih-En , Yang Ting-Hua , Hsu Po-Cheng , Kuo Chia-Hua , Lin Yi-Ying , Lai Wei-Yi , Kao Chung-Lan
Published: February 2021

A single-blind study to investigate the effects of noisy galvanic vestibular stimulation (nGVS) in straight walking and 2 Hz head yaw walking for healthy and bilateral vestibular hypofunction (BVH) participants in light and dark conditions. The optimal stimulation intensity for each participant was determined by calculating standing stability on a force plate while randomly applying six graded nGVS intensities (0–1000 µA). The chest–pelvic (C/P) ratio and lateral deviation of the center of mass (COM) were measured by motion capture during straight and 2 Hz head yaw walking in light and dark conditions. Participants were blinded to nGVS served randomly and imperceivably. Ten BVH patients and 16 healthy participants completed all trials. In the light condition, the COM lateral deviation significantly decreased only in straight walking (p = 0.037) with nGVS for the BVH. In the dark condition, both healthy (p = 0.026) and BVH (p = 0.017) exhibited decreased lateral deviation during nGVS. The C/P ratio decreased significantly in BVH for 2 Hz head yaw walking with nGVS (p = 0.005) in light conditions. This study demonstrated that nGVS effectively reduced walking deviations, especially in visual deprived condition for the BVH. Applying nGVS with different head rotation frequencies and light exposure levels may accelerate the rehabilitation process for patients with BVH.

Clinical Trial RegistrationThis clinical trial was prospectively registered atwww.clinicaltrials.govwith the Unique identifier: NCT03554941. Date of registration: (13/06/2018).
Extraction of ingredients from tea leaves using oxidative enzymatic reaction and optimization of extraction conditions
Authors: Pelalak Rasool , Khan Afrasyab , Zare Masoud Habibi , Sadeghi Mohammad Hasan , Marjani Azam
Published: February 2021

Peroxidase (POD) and polyphenol oxidase (PPO) are used as biocatalyst in many processes such as oxidization reactions, wastewater treatment, phenol synthesis and so on. The purpose of current study is enzymes extraction from biomass (tea leaves) as well as evaluation of their activation. Different parameters including temperature, buffer concentration, buffer type, buffer/tea leaves ratio, addition of high molecular weight polymers and emulsifiers, and pH were optimized in order to obtain the highest enzymes activity. Response Surface Methodology (RSM) procedure is employed for statistical analysis of enzymes extraction. It is understood from the result that PPO and POD possess the highest activity at temperatures of 25 °C and 50 °C, pH 7 and 5, buffer molarity of 0.1, and 0.05, buffer/tea leaves ratio = 5 for both, contact time = 20 min and 10 min, and presence of 6% and 3% PVP, 5% and 0% Tween 80 for PPO and POD, respectively. Amounts of highest activity for PPO and POD biocatalysts were calculated 0.42 U/mL and 0.025493 U/mL, respectively. Moreover, the entire inactivation of PPO took place after 30 min at 40 °C and 60 °C and 20 min at 80 °C. However, POD lost 35% of its activity after 30 min at 40 °C and 60 °C. The amount of 6% POD activity was kept after 45 min at 80 °C. Generally, it was indicated that POD was more resistant to thermal treatment than PPO.
Vibrational resonant inelastic X-ray scattering in liquid acetic acid: a ruler for molecular chain lengths
Authors: Savchenko Viktoriia , Brumboiu Iulia Emilia , Kimberg Victor , Odelius Michael , Krasnov Pavel , Liu Ji-Cai , Rubensson Jan-Erik , Björneholm Olle , Såthe Conny , Gråsjö Johan , Dong Minjie , Pietzsch Annette , Föhlisch Alexander , Schmitt Thorsten , McNally Daniel , Lu Xingye , Polyutov Sergey P. , Norman Patrick , Iannuzzi Marcella , Gel’mukhanov Faris , Ekholm Victor
Published: February 2021

Quenching of vibrational excitations in resonant inelastic X-ray scattering (RIXS) spectra of liquid acetic acid is observed. At the oxygen core resonance associated with localized excitations at the O–H bond, the spectra lack the typical progression of vibrational excitations observed in RIXS spectra of comparable systems. We interpret this phenomenon as due to strong rehybridization of the unoccupied molecular orbitals as a result of hydrogen bonding, which however cannot be observed in x-ray absorption but only by means of RIXS. This allows us to address the molecular structure of the liquid, and to determine a lower limit for the average molecular chain length.
Molecular function recognition by supervised projection pursuit machine learning
Authors: Grear Tyler , Avery Chris , Patterson John , Jacobs Donald J.
Published: February 2021

Identifying mechanisms that control molecular function is a significant challenge in pharmaceutical science and molecular engineering. Here, we present a novel projection pursuit recurrent neural network to identify functional mechanisms in the context of iterative supervised machine learning for discovery-based design optimization. Molecular function recognition is achieved by pairing experiments that categorize systems with digital twin molecular dynamics simulations to generate working hypotheses. Feature extraction decomposes emergent properties of a system into a complete set of basis vectors. Feature selection requires signal-to-noise, statistical significance, and clustering quality to concurrently surpass acceptance levels. Formulated as a multivariate description of differences and similarities between systems, the data-driven working hypothesis is refined by analyzing new systems prioritized by a discovery-likelihood. Utility and generality are demonstrated on several benchmarks, including the elucidation of antibiotic resistance in TEM-52 beta-lactamase. The software is freely available, enabling turnkey analysis of massive data streams found in computational biology and material science.
Wide-field fluorescent nanodiamond spin measurements toward real-time large-area intracellular thermometry
Authors: Nishimura Yushi , Oshimi Keisuke , Umehara Yumi , Kumon Yuka , Miyaji Kazu , Yukawa Hiroshi , Shikano Yutaka , Matsubara Tsutomu , Fujiwara Masazumi , Baba Yoshinobu , Teki Yoshio
Published: February 2021

Measuring optically detected magnetic resonance (ODMR) of diamond nitrogen vacancy centers significantly depends on the photon detectors used. We study camera-based wide-field ODMR measurements to examine the performance in thermometry by comparing the results to those of the confocal-based ODMR detection. We show that the temperature sensitivity of the camera-based measurements can be as high as that of the confocal detection and that possible artifacts of the ODMR shift are produced owing to the complexity of the camera-based measurements. Although measurements from wide-field ODMR of nanodiamonds in living cells can provide temperature precisions consistent with those of confocal detection, the technique requires the integration of rapid ODMR measurement protocols for better precisions. Our results can aid the development of camera-based real-time large-area spin-based thermometry of living cells.
Efficacy and safety of liver support devices in acute and hyperacute liver failure: a systematic review and network meta-analysis
Authors: Kanjo Anna , Ocskay Klementina , Gede Noémi , Kiss Szabolcs , Szakács Zsolt , Párniczky Andrea , Mitzner Steffen , Stange Jan , Hegyi Péter , Molnár Zsolt
Published: February 2021

Acute liver failure (ALF) is a potentially life-threatening condition. Liver support therapies can be applied as a bridging-to-transplantation or bridging-to-recovery; however, results of clinical trials are controversial. Our aim was to compare liver support systems in acute and hyperacute liver failure with network meta-analysis. After systematic search, randomized controlled trials (RCT) comparing liver support therapies in adults with acute or hyperacute liver failure were included. In-hospital mortality was the primary outcome, the secondary outcomes were hepatic encephalopathy and mortality-by-aetiology. A Bayesian-method was used to perform network meta-analysis and calculate surface under the cumulative ranking curve (SUCRA) values to rank interventions. Eleven RCTs were included. BioLogic-DT and molecular adsorbent recirculating system (MARS) resulted in the lowest mortality (SUCRAs: 76% and 73%, respectively). In non-paracetamol-poisoned patients, BioLogic-DT, charcoal hemoperfusion and MARS may be equally efficient regarding mortality (SUCRAs: 53%, 52% and 52%, respectively). Considering hepatic encephalopathy, extracorporeal liver assist device (ELAD) may be the most effective option (SUCRA: 78%). However, in pairwise meta-analysis, there were no statistically significant differences between the interventions in the outcomes. In conclusion, MARS therapy seems to be the best available option in reducing mortality. Further research is needed on currently available and new therapeutic modalities. (CRD42020160133).
Simple low dose radiography allows precise lung volume assessment in mice
Authors: Khan Amara , Markus Andrea , Rittmann Thomas , Albers Jonas , Alves Frauke , Hülsmann Swen , Dullin Christian
Published: February 2021

X-ray based lung function (XLF) as a planar method uses dramatically less X-ray dose than computed tomography (CT) but so far lacked the ability to relate its parameters to pulmonary air volume. The purpose of this study was to calibrate the functional constituents of XLF that are biomedically decipherable and directly comparable to that of micro-CT and whole-body plethysmography (WBP). Here, we developed a unique set-up for simultaneous assessment of lung function and volume using XLF, micro-CT and WBP on healthy mice. Our results reveal a strong correlation of lung volumes obtained from radiographic XLF and micro-CT and demonstrate that XLF is superior to WBP in sensitivity and precision to assess lung volumes. Importantly, XLF measurement uses only a fraction of the radiation dose and acquisition time required for CT. Therefore, the redefined XLF approach is a promising tool for preclinical longitudinal studies with a substantial potential of clinical translation.
Hidden by bias: how standard psychophysical procedures conceal crucial aspects of peripheral visual appearance
Authors: Yildirim Fazilet Zeynep , Coates Daniel R. , Sayim Bilge
Published: February 2021

The perception of a target depends on other stimuli surrounding it in time and space. This contextual modulation is ubiquitous in visual perception, and is usually quantified by measuring performance on sets of highly similar stimuli. Implicit or explicit comparisons among the stimuli may, however, inadvertently bias responses and conceal strong variability of target appearance. Here, we investigated the influence of contextual stimuli on the perception of a repeating pattern (a line triplet), presented in the visual periphery. In the neutral condition, the triplet was presented a single time to capture its minimally biased perception. In the similar and dissimilar conditions, it was presented within stimulus sets composed of lines similar to the triplet, and distinct shapes, respectively. The majority of observers reported perceiving a line pair in the neutral and dissimilar conditions, revealing ‘redundancy masking’, the reduction of the perceived number of repeating items. In the similar condition, by contrast, the number of lines was overestimated. Our results show that the similar context did not reveal redundancy masking which was only observed in the neutral and dissimilar context. We suggest that the influence of contextual stimuli has inadvertently concealed this crucial aspect of peripheral appearance.
Development and validation of a one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) for rapid detection of ZIKV in patient samples from Brazil
Authors: da Silva Severino Jefferson Ribeiro , Pardee Keith , Balasuriya Udeni B. R. , Pena Lindomar
Published: February 2021

We have previously developed and validated a one-step assay based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) for rapid detection of the Zika virus (ZIKV) from mosquito samples. Patient diagnosis of ZIKV is currently carried out in centralized laboratories using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR), which, while the gold standard molecular method, has several drawbacks for use in remote and low-resource settings, such as high cost and the need of specialized equipment. Point-of-care (POC) diagnostic platforms have the potential to overcome these limitations, especially in low-resource countries where ZIKV is endemic. With this in mind, here we optimized and validated our RT-LAMP assay for rapid detection of ZIKV from patient samples. We found that the assay detected ZIKV from diverse sample types (serum, urine, saliva, and semen) in as little as 20 min, without RNA extraction. The RT-LAMP assay was highly specific and up to 100 times more sensitive than RT-qPCR. We then validated the assay using 100 patient serum samples collected from suspected cases of arbovirus infection in the state of Pernambuco, which was at the epicenter of the last Zika epidemic. Analysis of the results, in comparison to RT-qPCR, found that the ZIKV RT-LAMP assay provided sensitivity of 100%, specificity of 93.75%, and an overall accuracy of 95.00%. Taken together, the RT-LAMP assay provides a straightforward and inexpensive alternative for the diagnosis of ZIKV from patients and has the potential to increase diagnostic capacity in ZIKV-affected areas, particularly in low and middle-income countries.
Positive effects of COVID-19 lockdown on air quality of industrial cities (Ankleshwar and Vapi) of Western India
Authors: Nigam Ritwik , Pandya Kanvi , Luis Alvarinho J. , Sengupta Raja , Kotha Mahender
Published: February 2021

On January 30, 2020, India recorded its first COVID-19 positive case in Kerala, which was followed by a nationwide lockdown extended in four different phases from 25th March to 31st May, 2020, and an unlock period thereafter. The lockdown has led to colossal economic loss to India; however, it has come as a respite to the environment. Utilizing the air quality index (AQI) data recorded during this adverse time, the present study is undertaken to assess the impact of lockdown on the air quality of Ankleshwar and Vapi, Gujarat, India. The AQI data obtained from the Central Pollution Control Board was assessed for four lockdown phases. We compared air quality data for the unlock phase with a coinciding period in 2019 to determine the changes in pollutant concentrations during the lockdown, analyzing daily AQI data for six pollutants (PM10, PM2.5, CO, NO2, O3, and SO2). A meta-analysis of continuous data was performed to determine the mean and standard deviation of each lockdown phase, and their differences were computed in percentage in comparison to 2019; along with the linear correlation analysis and linear regression analysis to determine the relationship among the air pollutants and their trend for the lockdown days. The results revealed different patterns of gradual to a rapid reduction in most of the pollutant concentrations (PM10, PM2.5, CO, SO2), and an increment in ozone concentration was observed due to a drastic reduction in NO2 by 80.18%. Later, increases in other pollutants were also observed as the restrictions were eased during phase-4 and unlock 1. The comparison between the two cities found that factors like distance from the Arabian coast and different industrial setups played a vital role in different emission trends.
Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue
Authors: Asakura Yoshifumi , Kondo Yohei , Aoki Kazuhiro , Naoki Honda
Published: February 2021

Collective cell migration is a fundamental process in embryonic development and tissue homeostasis. This is a macroscopic population-level phenomenon that emerges across hierarchy from microscopic cell-cell interactions; however, the underlying mechanism remains unclear. Here, we addressed this issue by focusing on epithelial collective cell migration, driven by the mechanical force regulated by chemical signals of traveling ERK activation waves, observed in wound healing. We propose a hierarchical mathematical framework for understanding how cells are orchestrated through mechanochemical cell-cell interaction. In this framework, we mathematically transformed a particle-based model at the cellular level into a continuum model at the tissue level. The continuum model described relationships between cell migration and mechanochemical variables, namely, ERK activity gradients, cell density, and velocity field, which could be compared with live-cell imaging data. Through numerical simulations, the continuum model recapitulated the ERK wave-induced collective cell migration in wound healing. We also numerically confirmed a consistency between these two models. Thus, our hierarchical approach offers a new theoretical platform to reveal a causality between macroscopic tissue-level and microscopic cellular-level phenomena. Furthermore, our model is also capable of deriving a theoretical insight on both of mechanical and chemical signals, in the causality of tissue and cellular dynamics.
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

Short-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

We 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

The 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

To 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

Rapid 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

Hepatocellular 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

The 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

The 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

Bitter 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

Recently, 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

In 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

Polyethylene 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.