bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structured illumination microscopy imaging reveals localization of replication protein A between chromosome lateral elements during mammalian meiosis
Authors: Yoon Seobin , Choi Eui-Hwan , Kim Jung-Woong , Kim Keun P. 
Published: August 2018

AbstractAn important event enabling meiotic prophase I to proceed is the close juxtaposition of conjoined chromosome axes of homologs and their assembly via an array of transverse filaments and meiosis-specific axial elements into the synaptonemal complex (SC). During meiosis, recombination requires the establishment of a platform for recombinational interactions between the chromosome axes and their subsequent stabilization. This is essential for ensuring crossover recombination and proper segregation of homologous chromosomes. Thus, well-established SCs are essential for supporting these processes. The regulation of recombination intermediates on the chromosome axis/SC and dynamic positioning of double-strand breaks are not well understood. Here, using super-resolution microscopy (structured illumination microscopy), we determined the localization of the replication protein A (RPA) complex on the chromosome axes in the early phase of leptonema/zygonema and within the CEs of SC in the pachynema during meiotic prophase in mouse spermatocytes. RPA, which marks the intermediate steps of pairing and recombination, appears in large numbers and is positioned on the chromosome axes at the zygonema. In the pachynema, RPA foci are reduced but do not completely disappear; instead, they are placed between lateral elements. Our results reveal the precise structure of SC and localization dynamics of recombination intermediates on meiocyte chromosomes undergoing homolog pairing and meiotic recombination.
Metabolic reprogramming of acute lymphoblastic leukemia cells in response to glucocorticoid treatment
Authors: Dyczynski Matheus , Vesterlund Mattias , Björklund Ann-Charlotte , Zachariadis Vasilios , Janssen Jerry , Gallart-Ayala Hector , Daskalaki Evangelia , Wheelock Craig E. , Lehtiö Janne , Grandér Dan , Tamm Katja Pokrovskaja , Nilsson Roland 
Published: August 2018

AbstractGlucocorticoids (GCs) are metabolic hormones with immunosuppressive effects that have proven effective drugs against childhood acute lymphoblastic leukemia (ALL). Yet, the role of metabolic reprogramming in GC-induced ALL cell death is poorly understood. GCs efficiently block glucose uptake and metabolism in ALL cells, but this does not fully explain the observed induction of autophagy and cell death. Here, we have performed parallel time-course proteomics, metabolomics, and isotope-tracing studies to examine in detail the metabolic effects of GCs on ALL cells. We observed metabolic events associated with growth arrest, autophagy, and catabolism prior to onset of apoptosis: nucleotide de novo synthesis was reduced, while certain nucleobases accumulated; polyamine synthesis was inhibited; and phosphatidylcholine synthesis was induced. GCs suppressed not only glycolysis but also entry of both glucose and glutamine into the TCA cycle. In contrast, expression of glutamine-ammonia ligase (GLUL) and cellular glutamine content was robustly increased by GC treatment, suggesting induction of glutamine synthesis, similar to nutrient-starved muscle. Modulating medium glutamine and dimethyl-α-ketoglutarate (dm-αkg) to favor glutamine synthesis reduced autophagosome content of ALL cells, and dm-αkg also rescued cell viability. These data suggest that glutamine synthesis affects autophagy and possibly onset of cell death in response to GCs, which should be further explored to understand mechanism of action and possible sources of resistance.
Overexpression of homeodomain-interacting protein kinase 2 (HIPK2) attenuates sepsis-mediated liver injury by restoring autophagy
Authors: Jiang Zhengyu , Bo Lulong , Meng Yan , Wang Chen , Chen Tianxing , Wang Changli , Yu Xiya , Deng Xiaoming 
Published: August 2018

AbstractSepsis is the leading cause of death in intensive care units worldwide. Autophagy has recently been shown to protect against sepsis-induced liver injury. Here, we investigated the roles of homeodomain-interacting protein kinase 2 (HIPK2) in the molecular mechanism of sepsis-induced liver injury. HIPK2 expression was reduced in sepsis-induced liver injury, and HIPK2 overexpression increased the survival rate and improved caecal ligation and puncture (CLP)-induced liver injury by reducing serum and liver aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) levels in mice with sepsis. HIPK2 overexpression significantly decreased CLP-induced release of inflammatory cytokines into the serum and attenuated oxidative stress-associated indicators in mice with CLP-induced liver injury, whereas HIPK2 knockdown produced the opposite results, suggesting that HIPK2 is a negative regulator of sepsis. Furthermore, HIPK2 overexpression inhibited lipopolysaccharide (LPS)-induced apoptosis of primary hepatocytes, increased the autophagic flux, and restored both autophagosome and autolysosome formation in the livers of CLP-induced mice by suppressing calpain signalling. Importantly, HIPK2 overexpression reduced the elevated cytosolic Ca2+ concentration in LPS-treated primary hepatocytes by interacting with calpain 1 and calmodulin. Finally, several anti-inflammatory drugs, including resveratrol, aspirin, vitamin E and ursolic acid, significantly increased the levels of the HIPK2 mRNA and protein by modulating promoter activity and the 3′-UTR stability of the HIPK2 gene. In conclusion, HIPK2 overexpression may improve sepsis-induced liver injury by restoring autophagy and thus might be a promising target for the clinical treatment of sepsis.
PARP12 (ARTD12) suppresses hepatocellular carcinoma metastasis through interacting with FHL2 and regulating its stability
Authors: Shao Changjuan , Qiu Yangyang , Liu Juan , Feng Huan , Shen Suqin , Saiyin Hexige , Yu Wenbo , Wei Youheng , Yu Long , Su Wei , Wu Jiaxue 
Published: August 2018

AbstractPARP12 is a mono-ADP-ribosyltransferase, but its function remains largely unknown. Here, we identified four-and-a-half LIM-only protein 2 (FHL2) as a functional partner of PARP12 through protein affinity purification. Although PARP12 did not mono-ADP-ribosylate FHL2 in vitro and in vivo, PARP12 deficiency decreased the protein level of FHL2 by promoting its ubiquitination and increased the expression level of transforming growth factor beta1 (TGF-β1), which is independent of PARP12 enzymatic activity. We also provided evidence that PARP12 deficiency increased the migration and invasion of hepatocellular carcinoma (HCC) cells and promoted HCC metastasis in vivo by regulating the epithelial–mesenchymal transition process. These results indicated that PARP12 is a tumor suppressor that plays an important role in HCC metastasis through the regulation of FHL2 stability and TGF-β1 expression.
Recombinant milk fat globule-EGF factor-8 reduces apoptosis via integrin β3/FAK/PI3K/AKT signaling pathway in rats after traumatic brain injury
Authors: Gao Yong-Yue , Zhang Zi-Huan , Zhuang Zong , Lu Yue , Wu Ling-Yun , Ye Zhen-nan , Zhang Xiang-Sheng , Chen Chun-Lei , Li Wei , Hang Chun-Hua 
Published: August 2018

AbstractAccumulating evidence suggests neuronal apoptosis has the potential to lead to more harmful effects in the pathological processes following traumatic brain injury (TBI). Previous studies have established that milk fat globule-EGF factor-8 (MFG-E8) provides neuroprotection through modulation of inflammation, oxidative stress, and especially apoptosis in cerebral ischemia and neurodegenerative disease. However, the effects of MFG-E8 on neuronal apoptosis in TBI have not yet been investigated. Therefore, we explored the role of MFG-E8 on anti-apoptosis and its potential mechanism following TBI. In the first set of experiments, adult male Sprague–Dawley (SD) rats were randomly divided into Sham and TBI groups that were each further divided into five groups representing different time points (6 h, 24 h, 72 h, and 7 days) (n = 9 each). Western blotting, quantitative real-time PCR, and immunofluorescence staining were performed to identify the expression and cellular localization of MFG-E8. In the second set of experiments, four groups were randomly assigned: Sham group, TBI + Vehicle group, and TBI + rhMFG-E8 (1 and 3 µg) (n = 15). Recombinant human MFGE8 (rhMFG-E8) was administrated as two concentrations through intracerebroventricular (i.c.v.) injection at 1 h after TBI induction. Brain water content, neurological severity score, western blotting, and immunofluorescence staining were measured at 24 and 72 h following TBI. In the final set of experiments, MFG-E8 siRNA (500 pmol/3 µl), integrin β3 siRNA (500 pmol/3 µl), and PI3K inhibitor LY294002 (5 and 20 µM) were injected i.c.v. and thereafter rats exposed to TBI. Western blotting, immunofluorescence staining, brain water content, neurological severity score, and Fluoro-Jade C (FJC) staining were used to investigate the effect of the integrin-β3/FAK/PI3K/AKT signaling pathway on MFG-E8-mediated anti-apoptosis after TBI. The expression of MFG-E8 was mainly located in microglial cells and increased to peak at 24 h after TBI. Treatment with rhMFG-E8 (3 µg) markedly decreased brain water content, improved neurological deficits, and reduced neuronal apoptosis at 24 and 72 h after TBI. rhMFG-E8 significantly enhanced the expression of integrin-β3/FAK/PI3K/AKT pathway-related components. Administration of integrin-β3 siRNA and LY294002 (5 and 20 µM) abolished the effect of rhMFG-E8 on anti-apoptosis and neuroprotection after TBI. This study demonstrated for the first time that rhMFG-E8 inhibits neuronal apoptosis and offers neuroprotection. This is suggested to occur through the modulation of the integrin-β3/FAK/PI3K/AKT signaling pathway, highlighting rhMFG-E8 as a potentially promising therapeutic strategy for TBI patients.
Social environment mediates cancer progression in Drosophila
Authors: Dawson Erika H. , Bailly Tiphaine P. M. , Dos Santos Julie , Moreno Céline , Devilliers Maëlle , Maroni Brigitte , Sueur Cédric , Casali Andreu , Ujvari Beata , Thomas Frederic , Montagne Jacques , Mery Frederic 
Published: August 2018

AbstractThe influence of oncogenic phenomena on the ecology and evolution of animal species is becoming an important research topic. Similar to host–pathogen interactions, cancer negatively affects host fitness, which should lead to the selection of host control mechanisms, including behavioral traits that best minimize the proliferation of malignant cells. Social behavior is suggested to influence tumor progression. While the ecological benefits of sociality in gregarious species are widely acknowledged, only limited data are available on the role of the social environment on cancer progression. Here, we exposed adult Drosophila, with colorectal-like tumors, to different social environments. We show how subtle variations in social structure have dramatic effects on the progression of tumor growth. Finally, we reveal that flies can discriminate between individuals at different stages of tumor development and selectively choose their social environment accordingly. Our study demonstrates the reciprocal links between cancer and social interactions and how sociality may impact health and fitness in animals and its potential implications for disease ecology.
A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target
Authors: Srivastava Prashant K. , van Eyll Jonathan , Godard Patrice , Mazzuferi Manuela , Delahaye-Duriez Andree , Van Steenwinckel Juliette , Gressens Pierre , Danis Benedicte , Vandenplas Catherine , Foerch Patrik , Leclercq Karine , Mairet-Coello Georges , Cardenas Alvaro , Vanclef Frederic , Laaniste Liisi , Niespodziany Isabelle , Keaney James , Gasser Julien , Gillet Gaelle , Shkura Kirill , Chong Seon-Ah , Behmoaras Jacques , Kadiu Irena , Petretto Enrico , Kaminski Rafal M. , Johnson Michael R. 
Published: August 2018

AbstractThe identification of drug targets is highly challenging, particularly for diseases of the brain. To address this problem, we developed and experimentally validated a general computational framework for drug target discovery that combines gene regulatory information with causal reasoning (“Causal Reasoning Analytical Framework for Target discovery”—CRAFT). Using a systems genetics approach and starting from gene expression data from the target tissue, CRAFT provides a predictive framework for identifying cell membrane receptors with a direction-specified influence over disease-related gene expression profiles. As proof of concept, we applied CRAFT to epilepsy and predicted the tyrosine kinase receptor Csf1R as a potential therapeutic target. The predicted effect of Csf1R blockade in attenuating epilepsy seizures was validated in three pre-clinical models of epilepsy. These results highlight CRAFT as a systems-level framework for target discovery and suggest Csf1R blockade as a novel therapeutic strategy in epilepsy. CRAFT is applicable to disease settings other than epilepsy.
Imaging soliton dynamics in optical microcavities
Authors: Yi Xu , Yang Qi-Fan , Yang Ki Youl , Vahala Kerry 
Published: August 2018

AbstractSolitons are self-sustained wavepackets that occur in many physical systems. Their recent demonstration in optical microresonators has provided a new platform for the study of nonlinear optical physics with practical implications for miniaturization of time standards, spectroscopy tools, and frequency metrology systems. However, despite its importance to the understanding of soliton physics, as well as development of new applications, imaging the rich dynamical behavior of solitons in microcavities has not been possible. These phenomena require a difficult combination of high-temporal-resolution and long-record-length in order to capture the evolving trajectories of closely spaced microcavity solitons. Here, an imaging method is demonstrated that visualizes soliton motion with sub-picosecond resolution over arbitrary time spans. A wide range of complex soliton transient behavior are characterized in the temporal or spectral domain, including soliton formation, collisions, spectral breathing, and soliton decay. This method can serve as a visualization tool for developing new soliton applications and understanding complex soliton physics in microcavities.
GePMI: A statistical model for personal intestinal microbiome identification
Authors: Wang Zicheng , Lou Huazhe , Wang Ying , Shamir Ron , Jiang Rui , Chen Ting 
Published: August 2018

AbstractHuman gut microbiomes consist of a large number of microbial genomes, which vary by diet and health conditions and from individual to individual. In the present work, we asked whether such variation or similarity could be measured and, if so, whether the results could be used for personal microbiome identification (PMI). To address this question, we herein propose a method to estimate the significance of similarity among human gut metagenomic samples based on reference-free, long k-mer features. Using these features, we find that pairwise similarities between the metagenomes of any two individuals obey a beta distribution and that a p value derived accordingly well characterizes whether two samples are from the same individual or not. We develop a computational framework called GePMI (Generating inter-individual similarity distribution for Personal Microbiome Identification) and apply it to several human gut metagenomic datasets (>300 individuals and >600 samples in total). From the results of GePMI, most of the human gut microbiomes can be identified (auROC = 0.9470, auPRC = 0.8702). Even after antibiotic treatment or fecal microbiota transplantation, the individual k-mer signature still maintains a certain specificity.
Glassy Dynamics in a heavy ion irradiated NbSe2 crystal
Authors: Eley S. , Khilstrom K. , Fotovat R. , Xiao Z. L. , Chen A. , Chen D. , Leroux M. , Welp U. , Kwok W. K. , Civale L. 
Published: August 2018

AbstractFascination with glassy states has persisted since Fisher introduced the vortex-glass as a new thermodynamic phase that is a true superconductor that lacks conventional long-range order. Though Fisher’s original model considered point disorder, it was later predicted that columnar defects (CDs) could also induce glassiness — specifically, a Bose-glass phase. In YBa2Cu3O7−x (YBCO), glassy states can cause distinct behavior in the temperature (T ) dependent rate of thermally activated vortex motion (S). The vortex-glass state produces a plateau in S(T ) whereas a Bose-glass can transition into a state hosting vortex excitations called double-kinks that can expand, creating a large peak in S(T ). Although glass phases have been well-studied in YBCO, few studies exist of other materials containing CDs that could contribute to distinguishing universal behavior. Here, we report on the effectiveness of CDs tilted ~30° from the c-axis in reducing S in a NbSe2 crystal. The magnetization is 5 times higher and S is minimized when the field is parallel to the defects versus aligned with the c-axis. We see signatures of glassiness in both field orientations, but do not observe a peak in S(T ) nor a plateau at values observed in YBCO. Finally, we discuss the possibility that competing disorder induces a field-orientation-driven transition from a Bose-glass to an anisotropic glass involving both point and columnar disorder.
A new meroterpenoid functions as an anti-tumor agent in hepatoma cells by downregulating mTOR activation and inhibiting EMT
Authors: Wan Haoqiang , Li Jiemei , Zhang Keda , Zou Xiaoting , Ge Lanlan , Zhu Fuqiang , Zhou Huirong , Gong Minna , Wang Tianwa , Chen Dongling , Peng Shusong , Zhou Boping , Zeng Xiaobin 
Published: August 2018

AbstractLiver cancer, also known as primary liver cancer, is cancer that starts in the liver. JNU-144, a new meroterpenoid purified from Lithospermum erythrorhizon, has exhibited promising anticancer activity; however, the molecular mechanisms of action of JNU-144 on malignant cells remain unclear. Our studies revealed that JNU-144 suppressed cell viability and proliferation in hepatoma cells by downregulating mTOR activation. Meanwhile, JNU-144 activated the intrinsic apoptosis pathway and subsequently triggered apoptotic cell death in SMMC-7721 cells. We also found that JNU-144 inhibited the epithelial–mesenchymal transition in both SMMC-7721 and HepG2 cells through reprogramming of epithelial–mesenchymal transition (EMT)-related gene expression or regulating protein instability. These findings indicate that JNU-144 exerts potent anticancer activity in hepatoma cells and may be developed as a potential therapeutic drug.
Quantitative progression of retinitis pigmentosa by optical coherence tomography angiography
Authors: Jauregui Ruben , Park Karen Sophia , Duong Jimmy K. , Mahajan Vinit B. , Tsang Stephen H. 
Published: August 2018

AbstractOptical coherence tomography angiography (OCT-A) is a non-invasive alternative to fluorescein angiography that allows for the study of the retinal and choroidal vasculatures. In this retrospective cohort study of 28 patients with retinitis pigmentosa (RP), we used OCT-A to quantify changes in perfusion density, foveal avascular zone (FAZ) area, and choriocapillaris blood flow over time and correlated these variables with ellipsoid zone (EZ) line width and best-corrected visual acuity (BCVA). Perfusion density decreased by 2.42 ± 0.62% per year at the superior capillary plexus (SCP) (P = 0.001) and 2.41 ± 0.76% per year at the deep capillary plexus (DCP) (P = 0.004). FAZ area increased by 0.078 ± 0.021 mm2 per year (P = 0.001) at the SCP and 0.152 ± 0.039 mm2 per year (P = 0.001) at the DCP. No changes were observed in the choriocapillaris blood flow. EZ line width had the strongest correlation to perfusion density at the SCP (r = 0.660 and 0.635, first and second visit, respectively, P = 0.001), while BCVA most strongly correlated with FAZ area at the SCP (r = 0.679 and 0.548, P = 0.001 and 0.003). Our results suggest that OCT-A is a useful tool for monitoring RP disease progression and may be used to measure retinal vascular parameters as outcomes in clinical trials.
GABAergic and cholinergic modulation of repetition suppression in inferior temporal cortex
Authors: Kuravi Pradeep , Vogels Rufin 
Published: August 2018

AbstractNeurons in many brain areas of different species reduce their response when a stimulus is repeated. Such adaptation or repetition suppression is prevalent in inferior temporal (IT) cortex. The mechanisms underlying repetition suppression in IT are still poorly understood. Studies in rodents and in-vitro experiments suggest that acetylcholine and GABA can contribute to repetition suppression by interacting with fatigue-related or local adaptation mechanisms. Here, we examined the contribution of cholinergic and GABAergic mechanisms to repetition suppression in macaque IT, using an adaptation paradigm in which familiar images were presented successively with a short interstimulus interval. We found that intracortical local injections of acetylcholine and of the GABAA receptor antagonist Gabazine both increased repetition suppression in awake macaque IT. The increased repetition suppression was observed for both spiking activity and local field potential power. The latter was present mainly for frequencies below 50 Hz, spectral bands that typically do not show consistent repetition suppression in IT. Although increased with drug application, repetition suppression remained stimulus selective. These findings agree with the hypothesis that repetition suppression of IT neurons mainly results from suppressed input from upstream and other IT neurons but depend less on intrinsic neuronal fatigue.
Promising post-consumer PET-derived activated carbon electrode material for non-enzymatic electrochemical determination of carbofuran hydrolysate
Authors: Ayyalusamy Sureshkumar , Mishra Susmita , Suryanarayanan Vembu 
Published: August 2018

AbstractIn this work, activated carbon (AC) materials, prepared from polyethylene terephthalate (PET) waste bottles were used as the sensing platform for the indirect detection of carbofuran. The morphology and surface properties of the PET-derived AC (PET-AC) were characterized by N2 adsorption/desorption isotherm, X-ray diffraction (XRD), field-emission scanning/transmission electron microscopy (FE-SEM/TEM) and Raman spectroscopy. The electrochemical activity of the PET-AC modified glassy carbon electrode (GCE) (PET-AC/GCE) was measured by cyclic voltammetry and amperometry. The enhanced surface area and desirable porosities of PET-AC are attributed for the superior electrocatalytic activity on the detection of carbofuran phenol, where, the proposed sensor shows low detection limit (0.03 µM) and remarkable sensitivity (0.11 µA µM−1 cm−2). The PET-AC/GCE holds high selectivity towards potentially interfering species. It also provides desirable stability, repeatability and reproducibility on detection of carbofuran phenol. Furthermore, the proposed sensor is utilized for the detection of carbofuran phenol in real sample applications. The above mentioned unique properties and desirable electrochemical performances suggest that the PET-derived AC is the most suitable carbonaceous materials for cost-effective and non-enzymatic electrochemical sensor.