bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNF168-mediated localization of BARD1 recruits the BRCA1-PALB2 complex to DNA damage
Authors: Krais John J. , Wang Yifan , Patel Pooja , Basu Jayati , Bernhardy Andrea J. , Johnson Neil 
Published: August 2021

AbstractDNA damage prompts a diverse range of alterations to the chromatin landscape. The RNF168 E3 ubiquitin ligase catalyzes the mono-ubiquitination of histone H2A at lysine (K)13/15 (mUb-H2A), forming a binding module for DNA repair proteins. BRCA1 promotes homologous recombination (HR), in part, through its interaction with PALB2, and the formation of a larger BRCA1-PALB2-BRCA2-RAD51 (BRCA1-P) complex. The mechanism by which BRCA1-P is recruited to chromatin surrounding DNA breaks is unclear. In this study, we reveal that an RNF168-governed signaling pathway is responsible for localizing the BRCA1-P complex to DNA damage. Using mice harboring a Brca1CC (coiled coil) mutation that blocks the Brca1-Palb2 interaction, we uncovered an epistatic relationship between Rnf168− and Brca1CC alleles, which disrupted development, and reduced the efficiency of Palb2-Rad51 localization. Mechanistically, we show that RNF168-generated mUb-H2A recruits BARD1 through a BRCT domain ubiquitin-dependent recruitment motif (BUDR). Subsequently, BARD1-BRCA1 accumulate PALB2-RAD51 at DNA breaks via the CC domain-mediated BRCA1-PALB2 interaction. Together, these findings establish a series of molecular interactions that connect the DNA damage signaling and HR repair machinery.
FGF2-primed 3D spheroids producing IL-8 promote therapeutic angiogenesis in murine hindlimb ischemia
Authors: Choi Jungkyun , Choi Wooshik , Joo Yunji , Chung Haeun , Kim Dokyun , Oh Seung Ja , Kim Sang-Heon 
Published: August 2021

AbstractPeripheral artery disease is a progressive, devastating disease that leads to critical limb ischemia (CLI). Therapeutic angiogenesis using stem cell therapy has emerged as a promising approach for its treatment; however, adapting cell-based therapy has been limited by poor cell survival and low treatment efficiency. To overcome unmet clinical needs, we developed a fibroblast growth factor 2 (FGF2)-immobilized matrix that enabled control of cell adhesion to the surface and exerted a priming effect on the cell. Human adipose-derived stem cells (hASCs) grown in this matrix formed a functionally enhanced cells spheroid (FECS-Ad) that secreted various angiogenic factors including interleukin-8 (IL-8). We demonstrated that IL-8 was upregulated by the FGF2-mediated priming effect during FECS-Ad formation. Immobilized FGF2 substrate induced stronger IL-8 expression than soluble FGF2 ligands, presumably through the FGFR1/JNK/NF-κB signaling cascade. In IL-8-silenced FECS-Ad, vascular endothelial growth factor (VEGF) expression was decreased and angiogenic potential was reduced. Intramuscular injection of FECS-Ad promoted angiogenesis and muscle regeneration in mouse ischemic tissue, while IL-8 silencing in FECS-Ad inhibited these effects. Taken together, our data demonstrate that IL-8 contributes to therapeutic angiogenesis and suggest that FECS-Ad generated using the MBP-FGF2 matrix might provide a reliable platform for developing therapeutic agents to treat CLI.
Sex differences in antipsychotic efficacy and side effects in schizophrenia spectrum disorder: results from the BeSt InTro study
Authors: Hoekstra Sanne , Bartz-Johannessen Christoffer , Sinkeviciute Igne , Reitan Solveig K. , Kroken Rune A. , Løberg Else-Marie , Larsen Tor K. , Rettenbacher Maria , Johnsen Erik , Sommer Iris E. 
Published: August 2021

AbstractCurrent guidelines for patients with schizophrenia spectrum disease do not take sex differences into account, which may result in inappropriate sex-specific treatment. In the BeSt InTro study, a total of 144 patients (93 men and 51 women) with a schizophrenia spectrum diagnosis and ongoing psychosis were included and randomized to amisulpride, aripiprazole, or olanzapine in flexible dose. This trial is registered with ClinicalTrials.gov (NCT01446328). Primary outcomes were sex differences in dose, dose-corrected serum levels, efficacy, and tolerability. Dosing was higher for men than for women in the aripiprazole group (p = 0.025) and, at trend level, in the olanzapine group (p = 0.056). Dose-corrected serum levels were 71.9% higher in women than in men for amisulpride (p = 0.019) and 55.8% higher in women than in men for aripiprazole (p = 0.049). In the amisulpride group, men had a faster decrease in psychotic symptoms than women (p = 0.003). Moreover, amisulpride was more effective than the other medications in men but not in women. Prolactin levels were higher in women than in men, especially for amisulpride (p < 0.001). Also, women had higher BMI increase on amisulpride compared to the two other antipsychotics (p < 0.001). We conclude that clinicians should be aware of the risks of overdosing in women, especially for amisulpride and aripiprazole. Amisulpride is highly effective in men, but in women, amisulpride showed more severe side effects and may thus not be the drug of first choice. Our study shows that sex differences should be taken into account in future studies on antipsychotics. Future research is warranted to evaluate these preliminary results.
Water budgeting in conservation agriculture-based sub-surface drip irrigation in tropical maize using HYDRUS-2D in South Asia
Authors: Patra Kiranmoy , Parihar C. M. , Nayak H. S. , Rana Biswajit , Singh V. K. , Jat S. L. , Panwar Sanjeev , Parihar M. D. , Singh L. K. , Sidhu H. S. , Gerard B. , Jat M. L. 
Published: August 2021

AbstractIn water scarce regions of South Asia, diversification of rice with maize is being advocated towards sustainability of cereal-based cropping systems. Adoption of innovative agronomic management practices, i.e., conservation agriculture (CA) and sub-surface drip irrigation (SSDI) are considered as key strategies for much needed interventions to address the challenges of water scarcity under projected climate change. Benefits from CA and SSDI concerning water economy are well-established, however, information about their complementarity and water budgeting in cereal-based systems are lacking. A field study was conducted with process-based model (HYDRUS-2D) to understand water transport, root water uptake and components of soil water balance in maize grown in rotation with wheat after five years of continuous adoption of conservation agriculture. In this study, altogether eight treatments comprising of 6 CA+ treatments (CA coupled with SSDI); permanent beds using sub-surface drip (PB-SSD) with (WR) and without (WOR) crop residue at different N rates, 0, 120 and 150 kg N ha−1 were compared with CA (PB using furrow irrigation-FI with crop residue-120 kg N ha−1) and conventional tillage practices (CT) (CT using FI without crop residue-120 kg N ha−1). Results showed that the model could simulate the daily changes in profile soil water content with reasonable accuracy in all the treatments. Simulated soil water balance indicated higher cumulative root water uptake (CRWU), lower cumulative evaporation (CE) and higher soil water retention in CA+ (PB-SSD+ crop residue at 150 and 120 kg N ha−1) than CA and CT plots. Hydrus-2D model efficiency > 0, RMSE between 0.009–0.026 and R2 value between 0.80–0.92 at P < 0.01 indicates that the model is performing efficiently. The mean evaporation from CA+ treatments was 10 and 36% less than CA and CT treatments, respectively. On average, CRWU under CA+ treatments were 14–48% higher than FI treatments. The mean cumulative deep drainage in CA+ plots was 80–100 mm less than CA and CT plots. In CA+ based plots significantly higher biomass production and radiation use efficiency were observed with reduced water use than CA and CT. Therefore, the study justifies the water-saving nature of CA+, while maintaining higher productivity and meeting the transpiration demand of crops and halting unnecessary evaporation and deep drainage losses.
Cx43 mediates changes in myofibroblast contraction and collagen release in human amniotic membrane defects after trauma
Authors: Costa Eleni , Okesola Babatunde O. , Thrasivoulou Christopher , Becker David L. , Deprest Jan A. , David Anna L. , Chowdhury Tina T. 
Published: August 2021

AbstractThe wound healing capacity of the fetal membranes after spontaneous or iatrogenic membrane rupture is unclear. We examined the healing mechanisms in amniotic membrane (AM) defects after trauma. Traumatised human AM defects were cultured for 4 days. Markers for nuclear (DAPI), cell type (vimentin, αSMA) and healing (Cx43, TGFβ1, collagen) were examined by immunofluorescence (IMF) confocal microscopy, Second Harmonic Generation (SHG) imaging and RT-qPCR. After trauma, AMCs and myofibroblasts migrated to the AM wound edge. Within four days, αSMA expressing myofibroblasts showed abundant Cx43 localized in the cytoplasmic processes. The highly contractile spindle-shaped myofibroblasts were present in the defect site and released collagen. In contrast, AMCs expressed vimentin and formed Cx43 plaques between cells found in the outer edges of the wound. Whilst AMCs were absent in the defect site, αSMA expressing myofibroblasts continued to elongate and polarize the collagen fibres. Both TGFβ1 and Cx43 gene expression were significantly increased after trauma. Cx43 has differential effects on AM cell populations that increase cellularity, contraction and potentially migration to the wound edge resulting in collagen polarisation in the AM defect site. Establishing how Cx43 regulates AM cell function could be an approach to repair defects in the membranes after trauma.
Comparative study of efficiency and characteristics of FMT and DRT installed in human cadavers for round-window stimulation
Authors: Shin Dong Ho , Kim Jong Hoon , Gottlieb Peter , Vaisbuch Yona , Puria Sunil , Cho Jin-Ho , Seong Ki Woong 
Published: August 2021

AbstractAcoustic hearing aids generate amplified sound in the ear canal, and they are the standard of care for patients with mild to moderate sensorineural hearing loss. However, because of their limited frequency bandwidth, gain, and feedback, there is substantial room for improvement. Active middle ear implants, which directly vibrate the middle ear and cochlea, are an alternative approach to conventional acoustic hearing aids. They provide an opportunity to improve sound quality and speech understanding with amplification rehabilitation. For floating-mass type and direct-rod type (DRT) middle ear transducers, a differential floating-mass transducer (DFMT) and a tri-coil bellows transducer (TCBT), respectively, were fabricated to measure the output characteristics in four human temporal bones. Both were fabricated to have similar output forces per unit input and were placed in four human temporal bones to measure their output performances. The TCBT resulted in higher output than did the DFMT throughout the audible frequency range, and the output was more prominent at lower frequency ranges. In this study, we showed that DRT was a more effective method for round window stimulation. Because of its frequency characteristics and vibration efficiency, this implantation method can be utilized as a driving solution for middle ear implants.
Improvement of quality of life and symptom burden after robot-assisted radical prostatectomy in patients with moderate to severe LUTS
Authors: Leyh-Bannurah Sami-Ramzi , Wagner Christian , Schuette Andreas , Liakos Nikolaos , Karagiotis Theodoros , Mendrek Mikolaj , Rachubinski Pawel , Urbanova Katarina , Oelke Matthias , Witt Jorn H. 
Published: August 2021

AbstractThe aim of this study was to assess clinically meaningful differences of preoperative lower urinary tract symptoms (LUTS) and quality of life (QoL) before and after robot-assisted radical prostatectomy (RARP). Therefore we identified 5506 RARP patients from 2007 to 2018 with completed International Prostate Symptom Score (IPSS) and -QoL questionnaires before and 12 months after RARP in our institution. Marked clinically important difference (MCID) was defined by using the strictest IPSS-difference of − 8 points. Multivariable logistic regression analyses (LRM) aimed to predict ∆IPSS ≤ − 8 and were restricted to RARP patients with preoperatively moderate (IPSS 8–19) vs. severe (IPSS 20–35) LUTS burden (n = 2305). Preoperative LUTS was categorized as moderate and severe in 37% (n = 2014) and 5.3% of the complete cohort (n = 291), respectively. Here, a postoperative ∆IPSS ≤ − 8, was reported in 38% vs. 90%. In LRM, younger age (OR 0.98, 95%CI 0.97–0.99; p = 0.007), lower BMI (OR 0.94, 95%CI 0.92–0.97; p < 0.001), higher preoperative LUTS burden (severe vs. moderate [REF.] OR 15.6, 95%CI 10.4–23.4; p < 0.001), greater prostate specimen weight (per 10 g, OR 1.12, 95%CI 1.07–1.16; p < 0.001) and the event of urinary continence recovery (OR 1.66 95%CI 1.25–2.21; p < 0.001) were independent predictors of a marked LUTS improvement after RARP. Less rigorous IPSS-difference of − 5 points yielded identical predictors. To sum up, in substantial proportions of patients with preoperative moderate or severe LUTS a marked improvement of LUTS and QoL can be expected at 12 months after RARP. LRM revealed greatest benefit in those patients with preoperatively greatest LUTS burden, prostate enlargement, lower BMI, younger age and the event of urinary continence recovery.
Identification and antimicrobial susceptibility profiles of Nocardia species clinically isolated in Japan
Authors: Toyokawa Masahiro , Ohana Noboru , Ueda Akiko , Imai Minako , Tanno Daiki , Honda Mutsuko , Takano Yukiko , Ohashi Kazutaka , Saito Kyoichi , Shimura Hiroki 
Published: August 2021

AbstractThe aims of the present study were to profile the antimicrobial susceptibility patterns of a diverse range of Nocardia species isolated in Japan, and to determine the ability of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for species/complex identification. Identification of 153 clinical isolates was performed by full-length 16S rRNA gene sequencing as a reference method to evaluate the usefulness of MALDI-TOF MS identification. Antimicrobial susceptibility testing (AST) for 14 antibiotics was performed using the broth microdilution method against 146 of the isolates. Among the total 153 clinical isolates, Nocardia farcinica complex (25%) was the most common species, followed by Nocardia cyriacigeorgica (18%), Nocardia brasiliensis (9%), Nocardia nova (8%), and Nocardia otitidiscaviarum (7%). Among 150 isolates identified to the species/complex level by 16S rRNA gene sequencing, MALDI-TOF MS with the use of a supplemental Nocardia library (JMLD library ver.ML01) correctly identified 97.3% (n = 146) to the species/complex level and 1.3% (n = 2) to the genus level. Among the 146 Nocardia isolates that underwent AST, the susceptibilities were 100% to linezolid, 96% to amikacin, 94% to trimethoprim-sulfamethoxazole, and 76% to imipenem. None of the trimethoprim-sulfamethoxazole-resistant isolates carried either plasmid-mediated sulfonamide-resistant genes (sul1, sul2) or trimethoprim-resistant genes (dfrA).
Identification of a novel inhibitor of liver cancer cell invasion and proliferation through regulation of Akt and Twist1
Authors: Ha Jain , Lee Sewoong , Park Jiyoung , Seo Jihye , Kang Eunjeong , Yoon Haelim , Kim Ba Reum , Lee Hyeon Kyu , Ryu Seong Eon , Cho Sayeon 
Published: August 2021

AbstractWhen primary cancer faces limited oxygen and nutrient supply, it undergoes an epithelial–mesenchymal transition, which increases cancer cell motility and invasiveness. The migratory and invasive cancer cells often exert aggressive cancer development or even cancer metastasis. In this study, we investigated a novel compound, 3-acetyl-5,8-dichloro-2-((2,4-dichlorophenyl)amino)quinolin-4(1H)-one (ADQ), that showed significant suppression of wound healing and cellular invasion. This compound also inhibited anchorage-independent cell growth, multicellular tumor spheroid survival/invasion, and metalloprotease activities. The anti-proliferative effects of ADQ were mediated by inhibition of the Akt pathway. In addition, ADQ reduced the expression of mesenchymal markers of cancer cells, which was associated with the suppressed expression of Twist1. In conclusion, ADQ successfully suppressed carcinogenic activity by inhibiting the Akt signaling pathway and Twist1, which suggests that ADQ may be an efficient candidate for cancer drug development.
Aggregation induced emission based active conjugated imidazole luminogens for visualization of latent fingerprints and multiple anticounterfeiting applications
Authors: Ravindra M. K. , Darshan G. P. , Lavanya D. R. , Mahadevan K. M. , Premkumar H. B. , Sharma S. C. , Adarsha H. , Nagabhushana H. 
Published: August 2021

AbstractAggregation-induced emission based organic heterocyclic luminogens bearing conjugated electronic structures showed much attention due to its excellent fluorescence in aggregation state. In this communication, a novel conjugated blue light emitting imidazole molecule is synthesized by one pot multicomponent reaction route is reported for the first time. The prepared molecule exhibits a strong fluorescence in aggregation state with exceptional properties, such as high purity, inexpensive, eco-friendly, large scale production, high photostability, etc. By considering these advantages, a new fluorescence based platform has been setup for in-situ visualization of latent fingerprints and its preservation by spray method followed by Poly(vinyl alcohol) masking. A clear and well defined fluorescence fingerprint images are noticed on variety of surfaces by revealing level 1–3 ridge features upon ultraviolet 365 nm light exposure. The dual nature of binding specificity as well as excellent fluorescence properties permits the visualization of latent fingerprints for longer durations (up to 365 days) with superior contrast, high sensitivity, efficiency, selectivity and minimal background hindrance. We further fabricated unclonable invisible security ink for various printing modes on valuable goods for protection against forging. The developed labels are displaying uniform distribution of ink and exceptional stability under various atmospheric environments. The development of long preservative information using aggregation-induced emission based luminogen opens up a new avenue in advanced forensic and data security applications.
Elementary calcium release events in the skeletal muscle cells of the honey bee Apis mellifera
Authors: Collet Claude , Charreton Mercédès , Szabo Laszlo , Takacs Marianna , Csernoch Laszlo , Szentesi Peter 
Published: August 2021

AbstractCalcium sparks are involved in major physiological and pathological processes in vertebrate muscles but have never been characterized in invertebrates. Here, dynamic confocal imaging on intact skeletal muscle cells isolated enzymatically from the adult honey bee legs allowed the first spatio-temporal characterization of subcellular calcium release events (CREs) in an insect species. The frequency of CREs, measured in x–y time lapse series, was higher than frequencies usually described in vertebrates. Honey bee CREs had a larger spatial spread at half maximum than their vertebrate counterparts and a slightly ellipsoidal shape, two characteristics that may be related to ultrastructural features specific to invertebrate cells. In line-scan experiments, the histogram of CREs’ duration followed a bimodal distribution, supporting the existence of both sparks and embers. Unlike in vertebrates, embers and sparks had similar amplitudes, a difference that could be related to genomic differences and/or excitation–contraction coupling specificities in honey bee skeletal muscle fibres. The first characterization of CREs from an arthropod which shows strong genomic, ultrastructural and physiological differences with vertebrates may help in improving the research field of sparkology and more generally the knowledge in invertebrates cell Ca2+ homeostasis, eventually leading to a better understanding of their roles and regulations in muscles but also the myotoxicity of new insecticides targeting ryanodine receptors.
A potential bat adenovirus-based oncolytic virus targeting canine cancers
Authors: Matsugo Hiromichi , Kitamura-Kobayashi Tomoya , Kamiki Haruhiko , Ishida Hiroho , Sekine Wataru , Takenaka-Uema Akiko , Nakagawa Takayuki , Murakami Shin , Horimoto Taisuke 
Published: August 2021

AbstractAlthough a canine adenovirus (CAdV)-based oncolytic virus (OV) candidate targeting canine tumors has been reported, its oncolytic effect could be attenuated by CAdV vaccine-induced neutralizing antibodies in dog patients. To circumvent this issue, we focused on the bat adenovirus (BtAdV) strain, which was previously isolated from healthy microbats. We previously showed that this virus replicated efficiently in canine cell lines and did not serologically cross-react with CAdVs, suggesting that it may offer the possibility of an OV candidate for canine tumors. Here, we tested the growth properties and cytotoxicity of the BtAdV Mm32 strain in a panel of canine tumor cells and found that its characteristics were equivalent to those of CAdVs. To produce an Mm32 construct with enhanced tumor specificity, we established a novel reverse genetics system for BtAdV based on bacterial artificial chromosomes, and generated a recombinant virus, Mm32-E1Ap + cTERTp, by inserting a tumor-specific canine telomerase reverse transcriptase promoter into its E1A regulatory region. The growth and cytotoxicity of this recombinant were superior to those of wild-type Mm32 in canine tumor cells, unlike in normal canine cells. These data suggest that Mm32-E1Ap + cTERTp could be a promising OV for alternative canine cancer therapies.
Coastal exposure and residents’ mental health in the affected areas by the 2011 Great East Japan Earthquake and Tsunami
Authors: Tashiro Ai , Kogure Mana , Nagata Shohei , Itabashi Fumi , Tsuchiya Naho , Hozawa Atsushi , Nakaya Tomoki 
Published: August 2021

AbstractNo previous study has ever explored the association between coastal exposure and the mental health of residents in a post-disaster context. Therefore, we aimed to confirm whether there was an association between sea visibility and coastal proximity and the mental health of coastal residents a devastating tsunami. We targeted 15 coastal municipalities located in the Miyagi Prefecture, and obtained data from a community-based cohort study. The baseline survey was initiated 2 years after the 2011 Great East Japan Earthquake and Tsunami and the secondary survey was initiated 6 years after the disaster. We applied multilevel mixed-effects models to the longitudinal data. Our outcome measure was the Kessler Psychological Distress Scale (K6) score. We assessed the data collected from 2,327 respondents on both surveys as of April 2018 for this ongoing cohort study. We found that neither sea visibility nor coastal proximity was significantly associated with the recovery of mental health after the disaster. However, we found a distinctive trend of mental health recovery in people who lived alone with a sea view, indicating that visibility of the sea had a negative effect on their mental health immediately after the GEJET, but that the negative effect was subsequently eliminated.