bluuebunny/crossref_metadata_2025_split huggingface dataset:
CaMKII/calpain interaction mediates ischemia/reperfusion injury in isolated rat hearts
Authors: Lu Hong-Ting , Feng Ren-Qian , Tang Jia-Kun , Zhou Jing-Jun , Gao Feng , Ren Jun 
Published: May 2020

AbstractPrevious studies indicated that Ca2+/calmodulin-dependent kinase II (CaMKII), a kinase involved in the modulation of ryanodine receptor activity, activates Ca2+-regulated protease μ-calpain to promote myocardial ischemia/reperfusion injury. This study was performed to explore the underlying mechanisms in CaMKII-induced calpain activation to better understand heart injury. To examine the Ca2+ paradox and ischemia/reperfusion injury, isolated rat hearts were subjected to a Ca2+-free solution for 3 min, or left coronary artery occlusion for 40 min, prior to restoration of normal perfusion. Blockade of trans-sarcoplasmic reticulum Ca2+ flux using ryanodine and thapsigargin failed to prevent Ca2+ paradox-induced heart injury. In contrast, the Ca2+ paradox increased CaMKII auto-phosphorylation at Thr287, while the CaMKII inhibitor KN-62 and the Na+/Ca2+ exchanger inhibitor KB-R7943 alleviated heart injury and calpain activity. Intriguingly, the binding of μ-calpain large subunit calpain-1 (CAPN1) to phospho-CaMKII was blunted by both inhibitors. Thus, a Ca2+ leak via the ryanodine receptor is not an essential element in CaMKII-elicited calpain activation. In hearts receiving vector injection, ischemia/reperfusion caused elevated calpain activity and α-fodrin degradation, along with membrane integrity damage, similar to the effects noted in control hearts. Importantly, all these alterations were diminished with delivery of adeno-associated virus expressing mutant CaMKIIδC T287A. Ischemia/reperfusion increased CaMKII auto-phosphorylation and binding of CAPN1 to phospho-CaMKII, and facilitated the translocation of phospho-CaMKII and CAPN1 to the plasma membrane, all of which were reversed by injecting CaMKII mutant. Furthermore, the relocation capacity and the interaction of CaMKII with CAPN1 appeared to be dependent upon CaMKII autophosphorylation, as its mutant delivery increased the level of CaMKII, but did not increase membrane content of CaMKII and CAPN1, or their interactions. Together, CaMKII/calpain interaction represents a new avenue for mediating myocardial ischemia/reperfusion injury, and CaMKII likely serves as both a kinase and a carrier, thereby promoting calpain membrane translocation and activation.
Gene expression trajectories during male and female reproductive development in balsam poplar (Populus balsamifera L.)
Authors: Cronk Quentin , Soolanayakanahally Raju , Bräutigam Katharina 
Published: May 2020

AbstractPlant reproductive development from the first appearance of reproductively committed axes through to floral maturation requires massive and rapid remarshalling of gene expression. In dioecious species such as poplar this is further complicated by divergent male and female developmental programs. We used seven time points in male and female balsam poplar (Populus balsamifera L.) buds and catkins representing the full annual flowering cycle, to elucidate the effects of time and sex on gene expression during reproductive development. Time (developmental stage) is dominant in patterning gene expression with the effect of sex nested within this. Here, we find (1) evidence for five successive waves of alterations to the chromatin landscape which may be important in setting the overall reproductive trajectory, regardless of sex. (2) Each individual developmental stage is further characterized by marked sex-differential gene expression. (3) Consistent sexually differentiated gene expression regardless of developmental stage reveal candidates for high-level regulators of sex and include the female-specific poplar ARR17 homologue. There is also consistent male-biased expression of the MADS-box genes PISTILLATA and APETALA3. Our work provides insights into expression trajectories shaping reproductive development, its potential underlying mechanisms, and sex-specific translation of the genome information into reproductive structures in balsam poplar.
30 years revisit survey for long-term changes in the Antarctic subtidal algal assemblage
Authors: Ko Young Wook , Choi Han-Gu , Lee Dong Seok , Kim Jeong Ha 
Published: May 2020

AbstractA long-term change of a subtidal macroalgal assemblage has been investigated in Maxwell Bay, King George Island (KGI) of the Antarctic coast by a revisit survey after 30 years. Field surveys were done by SCUBA diving at six sites in 2016–2018 to directly compare with the previous survey conducted in 1988–1993 at the same sites. The total number of macroalgal species was similar between the previous and the present survey, 25 and 27 species respectively. However, the macroalgal assemblage changed substantially with the average similarity of 48.2% between the two surveys. Also, the species-level abundance showed a high variability between surveys. On the other hand, over the 30 years interval there was little overall change at the between-site level hierarchical structure in the subtidal communities of Maxwell Bay. The sites near the penguin rookery consistently showed the highest biodiversity, indicating the importance of land-based nutrients input in Antarctic coastal habitats. A noticeable pattern change over 30 years was the increase of Desmarestia complex and Plocamium cartilagineum and the decrease of Himantothallus grandifolius. Both groups are still dominant, but the shift from Himantothallus to Desmarestia-Plocamium may reflects temperature rise on the Maxwell Bay coast compared to the past.
Performance of a convolutional neural network derived from an ECG database in recognizing myocardial infarction
Authors: Makimoto Hisaki , Höckmann Moritz , Lin Tina , Glöckner David , Gerguri Shqipe , Clasen Lukas , Schmidt Jan , Assadi-Schmidt Athena , Bejinariu Alexandru , Müller Patrick , Angendohr Stephan , Babady Mehran , Brinkmeyer Christoph , Makimoto Asuka , Kelm Malte 
Published: May 2020

AbstractArtificial intelligence (AI) is developing rapidly in the medical technology field, particularly in image analysis. ECG-diagnosis is an image analysis in the sense that cardiologists assess the waveforms presented in a 2-dimensional image. We hypothesized that an AI using a convolutional neural network (CNN) may also recognize ECG images and patterns accurately. We used the PTB ECG database consisting of 289 ECGs including 148 myocardial infarction (MI) cases to develop a CNN to recognize MI in ECG. Our CNN model, equipped with 6-layer architecture, was trained with training-set ECGs. After that, our CNN and 10 physicians are tested with test-set ECGs and compared their MI recognition capability in metrics F1 (harmonic mean of precision and recall) and accuracy. The F1 and accuracy by our CNN were significantly higher (83 ± 4%, 81 ± 4%) as compared to physicians (70 ± 7%, 67 ± 7%, P < 0.0001, respectively). Furthermore, elimination of Goldberger-leads or ECG image compression up to quarter resolution did not significantly decrease the recognition capability. Deep learning with a simple CNN for image analysis may achieve a comparable capability to physicians in recognizing MI on ECG. Further investigation is warranted for the use of AI in ECG image assessment.
MED15, transforming growth factor beta 1 (TGF-β1), FcγRIII (CD16), and HNK-1 (CD57) are prognostic biomarkers of oral squamous cell carcinoma
Authors: Elahi Maryam , Rakhshan Vahid 
Published: May 2020

AbstractOwing to the high incidence and mortality of oral squamous cell carcinoma (OSCC), knowledge of its diagnostic and prognostic factors is of significant value. The biomarkers ‘CD16, CD57, transforming growth factor beta 1 (TGF-β1), and MED15’ can play crucial roles in tumorigenesis, and hence might contribute to diagnosis, prognosis, and treatment. Since there was no previous study on MED15 in almost all cancers, and since the studies on diagnostic/prognostic values of the other three biomarkers were a few in OSCC (if any) and highly controversial, this study was conducted. Biomarker expressions in all OSCC tissues and their adjacent normal tissues available at the National Tumor Bank (n = 4 biomarkers × [48 cancers + 48 controls]) were estimated thrice using qRT-PCR. Diagnostic values of tumors were assessed using receiver-operator characteristic (ROC) curves. Factors contributing to patients’ survival over 10 years were assessed using multiple Cox regressions. ROC curves were used to estimate cut-off points for significant prognostic variables (α = 0.05). Areas under the curve pertaining to diagnostic values of all markers were non-significant (P > 0.15). Survival was associated positively with tumoral upregulation of TGF-β1 and downregulation of CD16, CD57, and MED15. It was also associated positively with younger ages, lower histological grades, milder Jacobson clinical TNM stages (and lower pathological Ns), smaller and thinner tumors, and surgery cases not treated with incisional biopsy (Cox regression,P < 0.05). The cut-off point for clinical stage –as the only variable with a significant area under the curve– was between the stages 2 and 3. Increased TGF-β1 and reduced CD16, CD57, and MED15 expressions in the tumor might independently favor the prognosis. Clinical TNM staging might be one of the most reliable prognostic factors, and stages above 2 can predict a considerably poorer prognosis.
Reciprocal semantic predictions drive categorization of scene contexts and objects even when they are separate
Authors: Leroy Anaïs , Faure Sylvane , Spotorno Sara 
Published: May 2020

AbstractVisual categorization improves when object-context associations in scenes are semantically consistent, thus predictable from schemas stored in long-term memory. However, it is unclear whether this is due to differences in early perceptual processing, in matching of memory representations or in later stages of response selection. We tested these three concurrent explanations across five experiments. At each trial, participants had to categorize a scene context and an object briefly presented within the same image (Experiment 1), or separately in simultaneous images (Experiments 2–5). We analyzed unilateral (Experiments 1, 3) and bilateral presentations (Experiments 2, 4, 5), and presentations on the screen’s horizontal midline (Experiments 1–2) and in the upper and lower visual fields (Experiments 3, 4). In all the experiments, we found a semantic consistency advantage for both context categorization and object categorization. This shows that the memory for object-context semantic associations is activated regardless of whether these two scene components are integrated in the same percept. Our study suggests that the facilitation effect of semantic consistency on categorization occurs at the stage of matching the percept with previous knowledge, supporting the object selection account and extending this framework to an object-context reciprocal influence on matching processes (object-context selection account).
Experimental observation of flat focusing mirror based on photonic jet effect
Authors: Minin Igor V. , Liu Cheng-Yang , Yang Yu-Chih , Staliunas Kestutis , Minin Oleg V. 
Published: May 2020

AbstractIn this work, we experimentally demonstrate that a thin rectangle dielectric-metal structure can have a function of a flat focusing mirror based on photonic jet effect in reflection mode. Using polydimethylsiloxane (PDMS) rectangle with size length of 10 μm and wavelength-scale thickness of 1 μm on the top of a silicon wafer, we have built a flat mirror which focuses an incident beam at the focal length changing from 1.38 μm to 11.67 μm upon tuning the beam incidence angle from 30° to 75°. The focusing properties of such a mirror persist in the wavelength range of 405 nm to 671 nm. Our approach can be extended to realize other optical functionalities by properly controlling rectangle dimensions and materials. This flat focusing mirror is able to guide the incident beam in free space without perceptible diffraction at the distance equal to the photonic jet length and suitable for small-scale photonic circuits.
Clinically relevant mutations in mycobacterial LepA cause rifampicin-specific phenotypic resistance
Authors: Wang Bi-Wei , Zhu Jun-Hao , Javid Babak 
Published: May 2020

AbstractAlthough all wild-type bacterial populations exhibit antibiotic tolerance, bacterial mutants with higher or lower tolerant subpopulation sizes have been described. We recently showed that in mycobacteria, phenotypically-resistant subpopulations can grow in bulk-lethal concentrations of rifampicin, a first-line anti-tuberculous antibiotic targeting RNA polymerase. Phenotypic resistance was partly mediated by paradoxical upregulation of RNA polymerase in response to rifampicin. However, naturally occurring mutations that increase tolerance via this mechanism had not been previously described. Here, we used transposon insertional mutagenesis and deep sequencing (Tnseq) to investigate rifampicin-specific phenotypic resistance using two different in vitro models of rifampicin tolerance in Mycobacterium smegmatis. We identify multiple genetic factors that mediate susceptibility to rifampicin. Disruption of one gene, lepA, a translation-associated elongation factor, increased rifampicin tolerance in all experimental conditions. Deletion of lepA increased the subpopulation size that is able to grow in bulk-lethal rifampicin concentrations via upregulation of basal rpoB expression. Moreover, homologous mutations in lepA that are found in clinical Mycobacterium tuberculosis (Mtb) isolates phenocopy lepA deletion to varying degrees. Our study identifies multiple genetic factors associated with rifampicin tolerance in mycobacteria, and may allow correlation of genetic diversity of clinical Mtb isolates with clinically important phenotypes such as treatment regimen duration.
Effect of temperature on accidental human mortality: A time-series analysis in Shenzhen, Guangdong Province in China
Authors: Lian Tingyu , Fu Yingbin , Sun Mingwei , Yin Mingjuan , Zhang Yan , Huang Lingfeng , Huang Jingxiao , Xu Ziqian , Mao Chen , Ni Jindong , Liu Gang 
Published: May 2020

AbstractHealth-risk assessments of temperature are central to determine total non-accidental human mortality; however, few studies have investigated the effect of temperature on accidental human mortality. We performed a time-series study combined with a distributed lag non-linear model (DLNM) to quantify the non-linear and delayed effects of daily mean temperature on accidental human mortality between 2013 and 2017 in Shenzhen, China. The threshold for effects of temperature on accidental human mortality occurred between 5.6 °C and 18.5 °C. Cold exposures, but not hot exposures, were significantly associated with accidental human mortality. All of the observed groups were susceptible to cold effects, with the strongest effects presented in females (relative risk [RR]: 3.14, 95% confidence interval (CI) [1.44–6.84]), followed by poorly educated people (RR: 2.63, 95% CI [1.59–4.36]), males (RR: 1.79, 95% CI [1.10–2.92]), and well-educated people (RR: 1.20, 95% CI [0.58–2.51]). Pooled estimates for cold effects at a lag of 0–21 days (d) were also stronger than hot effects at a lag of 0–2 d. Our results indicate that low temperatures increased the risk of accidental human mortality. Females and poorly educated people were more susceptible to the low temperatures. These findings imply that interventions which target vulnerable populations during cold days should be developed to reduce accidental human mortality risk.
Single-step fabrication and work function engineering of Langmuir-Blodgett assembled few-layer graphene films with Li and Au salts
Authors: Milošević Ivana R. , Vasić Borislav , Matković Aleksandar , Vujin Jasna , Aškrabić Sonja , Kratzer Markus , Griesser Thomas , Teichert Christian , Gajić Radoš 
Published: May 2020

AbstractTo implement large-area solution-processed graphene films in low-cost transparent conductor applications, it is necessary to have the control over the work function (WF) of the film. In this study we demonstrate a straightforward single-step chemical approach for modulating the work function of graphene films. In our approach, chemical doping of the film is introduced at the moment of its formation. The films are self-assembled from liquid-phase exfoliated few-layer graphene sheet dispersions by Langmuir-Blodgett technique at the water-air interfaces. To achieve a single-step chemical doping, metal standard solutions are introduced instead of water. Li standard solutions (LiCl, LiNO3, Li2CO3) were used as n-dopant, and gold standard solution, H(AuCl4), as p-dopant. Li based salts decrease the work function, while Au based salts increase the work function of the entire film. The maximal doping in both directions yields a significant range of around 0.7 eV for the work function modulation. In all cases when Li-based salts are introduced, electrical properties of the film deteriorate. Further, lithium nitrate (LiNO3) was selected as the best choice for n-type doping since it provides the largest work function modulation (by 400 meV), and the least influence on the electrical properties of the film.
Manipulating Sirtuin 3 pathway ameliorates renal damage in experimental diabetes
Authors: Locatelli Monica , Zoja Carlamaria , Zanchi Cristina , Corna Daniela , Villa Sebastian , Bolognini Silvia , Novelli Rubina , Perico Luca , Remuzzi Giuseppe , Benigni Ariela , Cassis Paola 
Published: May 2020

AbstractMore effective treatments for diabetic nephropathy remain a major unmet clinical need. Increased oxidative stress is one of the most important pathological mechanisms that lead to kidney damage and functional impairment induced by diabetes. Sirtuin 3 (SIRT3) is the main mitochondrial deacetylase and critically regulates cellular reactive oxygen species (ROS) production and detoxification. Honokiol is a natural biphenolic compound that, by activating mitochondrial SIRT3, can carry out anti-oxidant, anti-inflammatory and anti-fibrotic activities. Here, we sought to investigate the renoprotective effects of honokiol in BTBR ob/ob mice with type 2 diabetes. Diabetic mice were treated with vehicle or honokiol between the ages of 8 and 14 weeks. Wild-type mice served as controls. Renal Sirt3 expression was significantly reduced in BTBR ob/ob mice, and this was associated with a reduction in its activity and increased ROS levels. Selective activation of SIRT3 through honokiol administration translated into the attenuation of albuminuria, amelioration of glomerular damage, and a reduction in podocyte injury. SIRT3 activation preserved mitochondrial wellness through the activation of SOD2 and the restoration of PGC-1α expression in glomerular cells. Additionally, the protective role of SIRT3 in glomerular changes was associated with enhanced tubular Sirt3 expression and upregulated renal Nampt levels, indicating a possible tubule-glomerulus retrograde interplay, which resulted in improved glomerular SIRT3 activity. Our results demonstrate the hitherto unknown renoprotective effect of SIRT3 against diabetic glomerular disease and suggest that the pharmacological modulation of SIRT3 activity is a possible novel approach to treating diabetic nephropathy.
Characterization of tumour-infiltrating lymphocytes in a tumour rejection cynomolgus macaque model
Authors: Satooka Hiroki , Ishigaki Hirohito , Todo Kagefumi , Terada Koji , Agata Yasutoshi , Itoh Yasushi , Ogasawara Kazumasa , Hirata Takako 
Published: May 2020

AbstractImmunotherapy has emerged as a promising and effective treatment for cancer, yet the clinical benefit is still variable, in part due to insufficient accumulation of immune effector cells in the tumour microenvironment. Better understanding of tumour-infiltrating lymphocytes (TILs) from nonhuman primate tumours could provide insights into improving effector cell accumulation in tumour tissues during immunotherapy. Here, we characterize TILs in a cynomolgus macaque tumour model in which the tumours were infiltrated with CD4+ and CD8+ T cells and were eventually rejected. The majority of CD4+ and CD8+ TILs exhibited a CD45RA−CCR7− effector memory phenotype, but unlike circulating T cells, they expressed CD69, a marker for tissue-resident memory T (TRM) cells. CD69-expressing CD8+ TILs expressed high levels of the cytotoxic molecule granzyme B and the co-inhibitory receptor PD-1. Consistent with the TRM cell phenotype, CD8+ TILs minimally expressed CX3CR1 but expressed CXCR3 at higher levels than circulating CD8+ T cells. Meanwhile, CXCL9, CXCL10 and CXCL11, chemokine ligands for CXCR3, were expressed at high levels in the tumours, thus attracting CXCR3+CD8+ T cells. These results indicate that tumour-transplanted macaques can be a useful preclinical model for studying and optimizing T cell accumulation in tumours for the development of new immunotherapies.
MicroRNA-33a negatively regulates myoblast proliferation by targeting IGF1, follistatin and cyclin D1
Authors: Li Xinxin , Qiu Jiamin , Liu Hehe , Deng Yan , Hu Shenqiang , Hu Jiwei , Wang Yushi , Wang Jiwen 
Published: May 2020

Abstract
MiR-33a is found as a regulator of cell proliferation in many cancer cells. However, it remains unknown if and how miR-33a plays a role in myoblast proliferation. To investigate the effect of miR-33a on myoblast proliferation, miR-33a mimic or inhibitor was co-administered with or without insulin-like growth factor 1 (IGF1) to simulation myoblasts. Our study showed that up-regulation of miR-33a impaired myoblast proliferation, while down-regulation of miR-33a enhanced myoblast proliferation. Mechanistically, we examined that miR-33a can inhibit the transcription of IGF1, follistatin (FST) and cyclin D1 (CCND1) by targeting their 3′UTR region in both HEK293T cells and duck myoblasts. Moreover, up-regulation of miR-33a decreased and its down-regulation increased the mRNA expression of PI3K, Akt, mTOR and S6K. Importantly, the decreased PI3K, Akt, mTOR and S6K expression by miR-33a mimics was abrogated by co-administered with IGF1. Altogether, our results demonstrated that miR-33a may directly target IGF1, FST and CCND1 to inhibit myoblast proliferation via PI3K/Akt/mTOR signaling pathway. In conclusion, miR-33a is a potential negative regulator of myoblast proliferation and by modulating its expression could promote the early development of skeletal muscle.
Novel compound heterozygous EYS variants may be associated with arRP in a large Chinese pedigree
Authors: Wei Chunli , Xiao Ting , Cheng Jingliang , Fu Jiewen , Zhou Qi , Yang Lisha , Lv Hongbin , Fu Junjiang 
Published: May 2020

Abstract
As a genetically heterogeneous ocular dystrophy, gene mutations with autosomal recessive retinitis pigmentosa (arRP) in patients have not been well described. We aimed to detect the disease-causing genes and variants in a Chinese arRP family. In the present study, a large Chinese pedigree consisting of 31 members including a proband and another two patients was recruited; clinical examinations were conducted; next-generation sequencing using a gene panel was used for identifying pathogenic genes, and Sanger sequencing was performed for verification of mutations. Novel compound heterozygous variants c.G2504A (p.C835Y) and c.G6557A (p.G2186E) for the EYS gene were identified, which co-segregated with the clinical RP phenotypes. Sequencing of 100 ethnically matched normal controls didn’t found these mutations in EYS. Therefore, our study identified pathogenic variants in EYS that may cause arRP in this Chinese family. This is the first study to reveal the novel mutation in the EYS gene (c.G2504A, p.C835Y), extending its mutation spectrum. Thus, the EYS c.G2504A (p.C835Y) and c.G6557A (p.G2186E) variants may be the disease-causing missense mutations for RP in this large arRP family. These findings should be helpful for molecular diagnosis, genetic counseling and clinical management of arRP disease.