bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perilipin2 plays a positive role in adipocytes during lipolysis by escaping proteasomal degradation
Authors: Takahashi Yu , Shinoda Akihiro , Kamada Haruhiko , Shimizu Makoto , Inoue Jun , Sato Ryuichiro 
Published: February 2016

AbstractPerilipin2 (Plin2), also known as adipose differentiation-related protein (ADRP), or adipophilin, is a member of the PAT family involved in lipid droplet (LD) formation in the liver and peripheral tissues. Although Plin2 was originally identified as a highly expressed gene in adipocytes, its physiological role in mature adipocytes is largely unknown. In this report, we investigated the regulation of Plin2 expression and its function in differentiated adipocytes of mouse embryonic fibroblasts (MEFs). Plin2 mRNA levels increased during adipocyte differentiation whereas protein levels did not. Plin2 was degraded through the ubiquitin-proteasome pathway but was inhibited by lipolytic inducers. Furthermore, lentiviral-mediated Plin2 knockdown attenuated lipolysis in differentiated MEFs in a time-dependent manner. Oleic acid-induced LD formation enhanced Plin2 protein stability when it was localized to LDs. Furthermore, a mutational analysis revealed that the ubiquitination and degradation of Plin2 required both the second and third alanine in the N-terminal region. These results suggest that Plin2 is degraded in the cytosol in its N-terminal amino acid sequence-dependent manner and instead becomes stable when localized on LDs. Our findings highlight the relationship between protein stability and a previously unnoticed function of Plin2 during lipolysis in adipocytes.
Apocynin and ebselen reduce influenza A virus-induced lung inflammation in cigarette smoke-exposed mice
Authors: Oostwoud L. C. , Gunasinghe P. , Seow H. J. , Ye J. M. , Selemidis S. , Bozinovski S. , Vlahos R. 
Published: February 2016

AbstractInfluenza A virus (IAV) infections are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Oxidative stress is increased in COPD, IAV-induced lung inflammation and AECOPD. Therefore, we investigated whether targeting oxidative stress with the Nox2 oxidase inhibitors and ROS scavengers, apocynin and ebselen could ameliorate lung inflammation in a mouse model of AECOPD. Male BALB/c mice were exposed to cigarette smoke (CS) generated from 9 cigarettes per day for 4 days. On day 5, mice were infected with 1 × 104.5 PFUs of the IAV Mem71 (H3N1). BALF inflammation, viral titers, superoxide production and whole lung cytokine, chemokine and protease mRNA expression were assessed 3 and 7 days post infection. IAV infection resulted in a greater increase in BALF inflammation in mice that had been exposed to CS compared to non-smoking mice. This increase in BALF inflammation in CS-exposed mice caused by IAV infection was associated with elevated gene expression of pro-inflammatory cytokines, chemokines and proteases, compared to CS alone mice. Apocynin and ebselen significantly reduced the exacerbated BALF inflammation and pro-inflammatory cytokine, chemokine and protease expression caused by IAV infection in CS mice. Targeting oxidative stress using apocynin and ebselen reduces IAV-induced lung inflammation in CS-exposed mice and may be therapeutically exploited to alleviate AECOPD.
Macrophages programmed by apoptotic cells inhibit epithelial-mesenchymal transition in lung alveolar epithelial cells via PGE2, PGD2, and HGF
Authors: Yoon Young-So , Lee Ye-Ji , Choi Youn-Hee , Park Young Mi , Kang Jihee Lee 
Published: February 2016

AbstractApoptotic cell clearance results in the release of growth factors and the action of signaling molecules involved in tissue homeostasis maintenance. Here, we investigated whether and how macrophages programmed by apoptotic cells inhibit the TGF-β1-induced Epithelial-mesenchymal transition (EMT) process in lung alveolar epithelial cells. Treatment with conditioned medium derived from macrophages exposed to apoptotic cells, but not viable or necrotic cells, inhibited TGF-β1-induced EMT, including loss of E-cadherin, synthesis of N-cadherin and α-smooth muscle actin, and induction of EMT-activating transcription factors, such as Snail1/2, Zeb1/2, and Twist1. Exposure of macrophages to cyclooxygenase (COX-2) inhibitors (NS-398 and COX-2 siRNA) or RhoA/Rho kinase inhibitors (Y-27632 and RhoA siRNA) and LA-4 cells to antagonists of prostaglandin E2 (PGE2) receptor (EP4 [AH-23848]), PGD2 receptors (DP1 [BW-A868C] and DP2 [BAY-u3405]), or the hepatocyte growth factor (HGF) receptor c-Met (PHA-665752), reversed EMT inhibition by the conditioned medium. Additionally, we found that apoptotic cell instillation inhibited bleomycin-mediated EMT in primary mouse alveolar type II epithelial cells in vivo. Our data suggest a new model for epithelial cell homeostasis, by which the anti-EMT programming of macrophages by apoptotic cells may control the progressive fibrotic reaction via the production of potent paracrine EMT inhibitors.
Rapid Hydrogen Peroxide release from the coral Stylophora pistillata during feeding and in response to chemical and physical stimuli
Authors: Armoza-Zvuloni Rachel , Schneider Avi , Sher Daniel , Shaked Yeala 
Published: February 2016

AbstractCorals make use of different chemical compounds during interactions with prey, predators and aggressors. Hydrogen Peroxide (H2O2) is produced and released by a wide range of organisms as part of their defense against grazers or pathogens. In coral reefs, the large fluxes and relatively long half-life of H2O2, make it a potentially important info-chemical or defense molecule. Here we describe a previously unstudied phenomenon of rapid H2O2 release from the reef-building coral Stylophora pistillata during feeding on zooplankton and in response to chemical and physical stimuli. Following stimuli, both symbiotic and bleached corals were found to rapidly release H2O2 to the surrounding water for a short period of time (few minutes). The H2O2 release was restricted to the site of stimulus and an increase in physical stress and chemical stimuli concentration resulted in elevated H2O2 release. Omission of calcium (a key regulator of exocytotic processes) from the experimental medium inhibited H2O2 release. Hence we suggest that H2O2 is actively released in response to stimuli, rather than leaking passively from the coral tissue. We estimate that at the site of stimulus H2O2 can reach concentrations potentially high enough to deter predators or motile, potentially pathogenic, bacteria.
The Role of Physical Stabilization in Whole Blood Preservation
Authors: Wong Keith H. K. , Sandlin Rebecca D. , Carey Thomas R. , Miller Kathleen L. , Shank Aaron T. , Oklu Rahmi , Maheswaran Shyamala , Haber Daniel A. , Irimia Daniel , Stott Shannon L. , Toner Mehmet 
Published: February 2016

AbstractThe rapid degradation of blood ex vivo imposes logistical limitations on the utilization of blood-borne cells in medical diagnostics and scientific investigations. A fundamental but overlooked aspect in the storage of this fluid tissue is blood settling, which induces physical stress and compaction, aggregates blood cells and causes collateral damage due to leukocyte activation. Here we show that the polymer Ficoll 70 kDa stabilized blood samples and prevented blood settling over the course of 72 hours, primarily by inhibiting depletion-mediated red blood cell aggregation. Physical stabilization decreased echinocyte formation, improved leukocyte viability and inhibited the release of neutrophil elastase—a marker of neutrophil extracellular trap formation. In addition, Ficoll-stabilized blood was compatible with common leukocyte enrichment techniques including red blood cell lysis and immunomagnetic purification. This study showed for the first time that blood settling can be prevented using polymers and has implications in diagnostics.
Drug testing and flow cytometry analysis on a large number of uniform sized tumor spheroids using a microfluidic device
Authors: Patra Bishnubrata , Peng Chien-Chung , Liao Wei-Hao , Lee Chau-Hwang , Tung Yi-Chung 
Published: February 2016

AbstractThree-dimensional (3D) tumor spheroid possesses great potential as an in vitro model to improve predictive capacity for pre-clinical drug testing. In this paper, we combine advantages of flow cytometry and microfluidics to perform drug testing and analysis on a large number (5000) of uniform sized tumor spheroids. The spheroids are formed, cultured and treated with drugs inside a microfluidic device. The spheroids can then be harvested from the device without tedious operation. Due to the ample cell numbers, the spheroids can be dissociated into single cells for flow cytometry analysis. Flow cytometry provides statistical information in single cell resolution that makes it feasible to better investigate drug functions on the cells in more in vivo-like 3D formation. In the experiments, human hepatocellular carcinoma cells (HepG2) are exploited to form tumor spheroids within the microfluidic device and three anti-cancer drugs: Cisplatin, Resveratrol and Tirapazamine (TPZ) and their combinations are tested on the tumor spheroids with two different sizes. The experimental results suggest the cell culture format (2D monolayer vs. 3D spheroid) and spheroid size play critical roles in drug responses and also demonstrate the advantages of bridging the two techniques in pharmaceutical drug screening applications.
Probing the phenomenon of trained immunity in invertebrates during a transgenerational study, using brine shrimp Artemia as a model system
Authors: Norouzitallab Parisa , Baruah Kartik , Biswas Priyanka , Vanrompay Daisy , Bossier Peter 
Published: February 2016

AbstractThe invertebrate’s innate immune system was reported to show some form of adaptive features, termed trained immunity. However, the memory characteristics of innate immune system and the mechanisms behind such phenomena remain unclear. Using the invertebrate model Artemia, we verified the possibility or impossibility of trained immunity, examining the presence or absence of enduring memory against homologous and heterologous antigens (Vibrio spp.) during a transgenerational study. We also determined the mechanisms behind such phenomenon. Our results showed the occurrence of memory and partial discrimination in Artemia’s immune system, as manifested by increased resistance, for three successive generations, of the progenies of Vibrio-exposed ancestors towards a homologous bacterial strain, rather than to a heterologous strain. This increased resistance phenotype was associated with elevated levels of hsp70 and hmgb1 signaling molecules and alteration in the expression of key innate immunity-related genes. Our results also showed stochastic pattern in the acetylation and methylation levels of H4 and H3K4me3 histones, respectively, in the progenies whose ancestors were challenged. Overall results suggest that innate immune responses in invertebrates have the capacity to be trained and epigenetic reprogramming of (selected) innate immune effectors is likely to have central place in the mechanisms leading to trained immunity.
Microphthalmia-associated transcription factor regulates the visual cycle genes Rlbp1 and Rdh5 in the retinal pigment epithelium
Authors: Wen Bin , Li Shuang , Li Huirong , Chen Yu , Ma Xiaoyin , Wang Jing , Lu Fan , Qu Jia , Hou Ling 
Published: February 2016

AbstractRegeneration of the visual pigment by cells of the retinal pigment epithelium (RPE) is fundamental to vision. Here we show that the microphthalmia-associated transcription factor, MITF, which plays a central role in the development and function of RPE cells, regulates the expression of two visual cycle genes, Rlbp1 which encodes retinaldehyde binding protein-1 (RLBP1) and Rdh5, which encodes retinol dehydrogenase-5 (RDH5). First, we found that Rlbp1 and Rdh5 are downregulated in optic cups and presumptive RPEs of Mitf-deficient mouse embryos. Second, experimental manipulation of MITF levels in human RPE cells in culture leads to corresponding modulations of the endogenous levels of RLBP1 and RDH5. Third, the retinal degeneration associated with the disruption of the visual cycle in Mitf-deficient mice can be partially corrected both structurally and functionally by an exogenous supply of 9-cis-retinal. We conclude that the expression of Rlbp1 and Rdh5 critically depends on functional Mitf in the RPE and suggest that MITF has an important role in controlling retinoid processing in the RPE.
Detection of Brownian Torque in a Magnetically-Driven Rotating Microsystem
Authors: Romodina Maria N. , Lyubin Evgeny V. , Fedyanin Andrey A. 
Published: February 2016

AbstractThermal fluctuations significantly affect the behavior of microscale systems rotating in shear flow, such as microvortexes, microbubbles, rotating micromotors, microactuators and other elements of lab-on-a-chip devices. The influence of Brownian torque on the motion of individual magnetic microparticles in a rotating magnetic field is experimentally determined using optical tweezers. Rotational Brownian motion induces the flattening of the breakdown transition between the synchronous and asynchronous modes of microparticle rotation. The experimental findings regarding microparticle rotation in the presence of Brownian torque are compared with the results of numerical Brownian dynamics simulations.
Risk Factors for Steatorrhea in Chronic Pancreatitis: A Cohort of 2,153 Patients
Authors: Li Bai-Rong , Pan Jun , Du Ting-Ting , Liao Zhuan , Ye Bo , Zou Wen-Bin , Chen Hui , Ji Jun-Tao , Zheng Zhao-Hong , Wang Dan , Lin Jin-Huan , Ning Shou-Bin , Hu Liang-Hao , Li Zhao-Shen 
Published: February 2016

AbstractThis study aimed to investigate the occurrence of and determine the risk factors for steatorrhea in chronic pancreatitis (CP). It was based on analysis of both retrospectively and prospectively acquired database for CP patients admitted to our center from January 2000 to December 2013. Demographic data, course of disease, medical history and follow-up evaluations of patients were documented in detail. Cumulative rate of steatorrhea was calculated by using the Kaplan–Meier method. For risk factor analysis, multivariate analysis by Cox proportional hazards regression model was performed. A total of 2,153 CP patients were included with a mean follow-up duration of 9.3 years. Approximately 14% (291/2,153) of CP patients presented with steatorrhea at diagnosis of CP. Cumulative rates of steatorrhea at 1, 5, 10 and 20 years after diagnosis of CP were 4.27% (95% CI: 3.42%–5.34%), 12.53% (95% CI: 10.74%–14.59%), 20.44% (95% CI: 17.37%–23.98%) and 30.82% (95% CI: 20.20%–45.21%), respectively. Male gender (HR = 1.771, p = 0.004), diabetes (HR = 1.923, p < 0.001), alcohol abuse (HR = 1.503, p = 0.025) and pancreaticoduodenectomy (HR = 2.901, p < 0.001) were independent risk factors for steatorrhea while CP in adolescents (HR = 0.433, p = 0.009) was a protective factor. In conclusion, male gender, adult, diabetes, alcohol abuse and pancreaticoduodenectomy lead to increased risk of steatorrhea in CP patients.
Evidence from Multiple Species that Spider Silk Glue Component ASG2 is a Spidroin
Authors: Collin Matthew A. , Clarke Thomas H. , Ayoub Nadia A. , Hayashi Cheryl Y. 
Published: February 2016

AbstractSpiders in the superfamily Araneoidea produce viscous glue from aggregate silk glands. Aggregate glue coats prey-capture threads and hampers the escape of prey from webs, thereby increasing the foraging success of spiders. cDNAs for Aggregate Spider Glue 1 (ASG1) and 2 (ASG2) have been previously described from the golden orb-weaver, Nephila clavipes and Western black widow, Latrodectus hesperus. To further investigate aggregate glues, we assembled ASG1 and ASG2 from genomic target capture libraries constructed from three species of cob-web weavers and three species of orb-web weavers, all araneoids. We show that ASG1 is unlikely to be a glue, but rather is part of a widespread arthropod gene family, the peritrophic matrix proteins. For ASG2, we demonstrate its remarkable architectural and sequence similarities to spider silk fibroins, indicating that ASG2 is a member of the spidroin gene family. Thus, spidroins have diversified into glues in addition to task-specific, high performance fibers.
D-β-aspartyl residue exhibiting uncommon high resistance to spontaneous peptide bond cleavage
Authors: Aki Kenzo , Okamura Emiko 
Published: February 2016

AbstractAlthough L-amino acids were selected as main constituents of peptides and proteins during chemical evolution, D-aspartyl (Asp) residue is found in a variety of living tissues. In particular, D-β-Asp is thought to be stable than any other Asp isomers and this could be a reason for gradual accumulation in abnormal proteins and peptides to modify their structures and functions. It is predicted that D-β-Asp shows high resistance to biomolecular reactions. For instance, less reactivity of D-β-Asp is expected to bond cleavage, although such information has not been provided yet. In this work, the spontaneous peptide bond cleavage was compared between Asp isomers, by applying real-time solution-state NMR to eye lens αΑ-crystallin 51–60 fragment, S51LFRTVLD58SG60 and αΒ-crystallin 61–67 analog, F61D62TGLSG67 consisting of L-α- and D-β-Asp 58 and 62, respectively. Kinetic analysis showed how tough the uncommon D-β-Asp residue was against the peptide bond cleavage as compared to natural L-α-Asp. Differences in pKa and conformation between L-α- and D-β-Asp side chains were plausible factors to determine reactivity of Asp isomers. The present study, for the first time, provides a rationale to explain less reactivity of D-β-Asp to allow abnormal accumulation.
Cyclin-dependent kinase 2 protects podocytes from apoptosis
Authors: Saurus Pauliina , Kuusela Sara , Dumont Vincent , Lehtonen Eero , Fogarty Christopher L. , Lassenius Mariann I. , Forsblom Carol , Lehto Markku , Saleem Moin A. , Groop Per-Henrik , Lehtonen Sanna 
Published: February 2016

AbstractLoss of podocytes is an early feature of diabetic nephropathy (DN) and predicts its progression. We found that treatment of podocytes with sera from normoalbuminuric type 1 diabetes patients with high lipopolysaccharide (LPS) activity, known to predict progression of DN, downregulated CDK2 (cyclin-dependent kinase 2). LPS-treatment of mice also reduced CDK2 expression. LPS-induced downregulation of CDK2 was prevented in vitro and in vivo by inhibiting the Toll-like receptor (TLR) pathway using immunomodulatory agent GIT27. We also observed that CDK2 is downregulated in the glomeruli of obese Zucker rats before the onset of proteinuria. Knockdown of CDK2, or inhibiting its activity with roscovitine in podocytes increased apoptosis. CDK2 knockdown also reduced expression of PDK1, an activator of the cell survival kinase Akt and reduced Akt phosphorylation. This suggests that CDK2 regulates the activity of the cell survival pathway via PDK1. Furthermore, PDK1 knockdown reduced the expression of CDK2 suggesting a regulatory loop between CDK2 and PDK1. Collectively, our data show that CDK2 protects podocytes from apoptosis and that reduced expression of CDK2 associates with the development of DN. Preventing downregulation of CDK2 by blocking the TLR pathway with GIT27 may provide a means to prevent podocyte apoptosis and progression of DN.
Cytomegalovirus-based vaccine expressing Ebola virus glycoprotein protects nonhuman primates from Ebola virus infection
Authors: Marzi Andrea , Murphy Aisling A. , Feldmann Friederike , Parkins Christopher J. , Haddock Elaine , Hanley Patrick W. , Emery Matthew J. , Engelmann Flora , Messaoudi Ilhem , Feldmann Heinz , Jarvis Michael A. 
Published: February 2016

AbstractEbolaviruses pose significant public health problems due to their high lethality, unpredictable emergence, and localization to the poorest areas of the world. In addition to implementation of standard public health control procedures, a number of experimental human vaccines are being explored as a further means for outbreak control. Recombinant cytomegalovirus (CMV)-based vectors are a novel vaccine platform that have been shown to induce substantial levels of durable, but primarily T-cell-biased responses against the encoded heterologous target antigen. Herein, we demonstrate the ability of rhesus CMV (RhCMV) expressing Ebola virus (EBOV) glycoprotein (GP) to provide protective immunity to rhesus macaques against lethal EBOV challenge. Surprisingly, vaccination was associated with high levels of GP-specific antibodies, but with no detectable GP-directed cellular immunity.
Effect of excessive CO2 on physiological functions in coastal diatom
Authors: Liu Feng-Jiao , Li Shun-Xing , Huang Bang-Qin , Zheng Feng-Ying , Huang Xu-Guang 
Published: February 2016

AbstractRising dissolution of anthropogenic CO2 in seawater may directly/indirectly cause ocean acidification and desalination. However, little is known about coastal physiological functions sensitivity to these processes. Here we show some links between ocean acidification/desalination and physiological functions in Thalassiosira weissflogii. Cell density (CD), protein, chlorophyll a (Chl a), malonaldehyde (MDA), superoxide dismutase (SOD), and carbonic anhydrase (CAs) were determined for the assessment of algal biomass, nutritional value, photosynthesis and respiration, lipid peroxidation, antioxidant capacity, and carbon sequestration ability. The influence of pH on the algal Chl a and MDA were extremely significant (P < 0.01). Salinity (S) on cell density and acidity (pH) on protein was significant (0.01 < P < 0.05). Additionally, a significant negative-correlation was observed between cell density and CAs. CAs and SOD had negatively correlations with CD, Chl a, protein, and MDA under pH or S influence, but positive correlation between themselves. Coastal physiological functions were affected by increasing order was acidification < acidification + desalination < desalination for Chl a and protein, desalination < acidification + desalination < acidification for SOD and CAs. Thus, the ongoing excessive CO2-driven ocean acidification and desalination should be of high attention when assessing the risks of climate change on coastal phytoplankton.
Mechanisms and consequences of ATMIN repression in hypoxic conditions: roles for p53 and HIF-1
Authors: Leszczynska Katarzyna B. , Göttgens Eva-Leonne , Biasoli Deborah , Olcina Monica M. , Ient Jonathan , Anbalagan Selvakumar , Bernhardt Stephan , Giaccia Amato J. , Hammond Ester M. 
Published: February 2016

AbstractHypoxia-induced replication stress is one of the most physiologically relevant signals known to activate ATM in tumors. Recently, the ATM interactor (ATMIN) was identified as critical for replication stress-induced activation of ATM in response to aphidicolin and hydroxyurea. This suggests an essential role for ATMIN in ATM regulation during hypoxia, which induces replication stress. However, ATMIN also has a role in base excision repair, a process that has been demonstrated to be repressed and less efficient in hypoxic conditions. Here, we demonstrate that ATMIN is dispensable for ATM activation in hypoxia and in contrast to ATM, does not affect cell survival and radiosensitivity in hypoxia. Instead, we show that in hypoxic conditions ATMIN expression is repressed. Repression of ATMIN in hypoxia is mediated by both p53 and HIF-1α in an oxygen dependent manner. The biological consequence of ATMIN repression in hypoxia is decreased expression of the target gene, DYNLL1. An expression signature associated with p53 activity was negatively correlated with DYNLL1 expression in patient samples further supporting the p53 dependent repression of DYNLL1. Together, these data demonstrate multiple mechanisms of ATMIN repression in hypoxia with consequences including impaired BER and down regulation of the ATMIN transcriptional target, DYNLL1.