bluuebunny/crossref_metadata_2025_split huggingface dataset:
Summertime Atmospheric Boundary Layer Gradients of O2 and CO2 over the Southern Ocean
Authors: Morgan Eric J. , Stephens Britton B. , Long Matthew C. , Keeling Ralph F. , Bent Jonathan D. , McKain Kathryn , Sweeney Colm , Hoecker‐Martínez Martín S. , Kort Eric A. 
Published: November 2019

AbstractWe present airborne observations of the vertical gradient of atmospheric oxygen (δ(O2/N2)) and carbon dioxide (CO2) through the atmospheric boundary layer (BL) over the Drake Passage region of the Southern Ocean, during the O2/N2 Ratio and CO2 Airborne Southern Ocean Study, from 15 January to 29 February 2016. Gradients were predominately anticorrelated, with excesses of δ(O2/N2) and depletions of CO2 found within the boundary layer, relative to a mean reference height of 1.7 km. Through analysis of the molar ratio of the gradients (GR), the behavior of other trace gases measured in situ, and modeling experiments with the Community Earth System Model, we found that the main driver of gradients was air‐sea exchange of O2 and CO2 driven by biological processes, more so than solubility effects. An exception to this was in the eastern Drake Passage, where positive GRs were occasionally observed, likely due to the dominance of thermal forcing on the air‐sea flux of both species. GRs were more spatially consistent than the magnitudes of the gradients, suggesting that GRs can provide integrated process constraints over broad spatial scales. Based on the model simulation within a domain bounded by 45°S, 75°S, 100°W, and 45°W, we show that the sampling density of the campaign was such that the observed mean GR (± standard error), −4.0± 0.8 mol O2 per mol CO2, was a reasonable proxy for both the mean GR and the mean molar ratio of air‐sea fluxes of O2 and CO2 during the O2/N2 Ratio and CO2 Airborne Southern Ocean Study.
The Importance of Monitoring Interval for Rockfall Magnitude‐Frequency Estimation
Authors: Williams Jack G. , Rosser Nick J. , Hardy Richard J. , Brain Matthew J. 
Published: November 2019

AbstractRockfalls commonly exhibit power law volume‐frequency distributions, where fewer large events are observed relative to more numerous small events. Within most inventories, the smallest rockfalls are the most difficult to detect and so may not be adequately represented. A primary challenge occurs when neighboring events within a single monitoring interval are recorded as one, producing ambiguity in event location, timing, volume, and frequency. Identifying measurement intervals that minimize these uncertainties is therefore essential. To address this, we use an hourly data set comprising 8,987 3‐D point clouds of a cliff that experiences frequent rockfalls. Multiple rockfall inventories are derived from this data set using change detections for the same 10‐month period, but over different monitoring intervals. The power law describing the probability distribution of rockfall volumes is highly sensitive to monitoring interval. The exponent,β, is stable for intervals >12 hr but increases nonlinearly over progressively short timescales. This change is manifested as an increase in observed rockfall numbers, from 1.4 × 103(30 day intervals) to 1.4 × 104(1 hr intervals), and a threefold reduction in mean rockfall volume. When the monitoring interval exceeds 4 hr, the geometry of detected rockfalls becomes increasingly similar to that of blocks defined by rock mass structure. This behavior change reveals a time‐dependent component to rockfall occurrence, where smaller rockfalls (identifiable from more frequent monitoring) are more sensitive to progressive deformation of the rock mass. Acquiring complete inventories and attributing discrete controls over rockfall occurrence may therefore only be achievable with high‐frequency monitoring, dependent upon local lithology.
Prostaglandin D2 stimulates phenotypic changes in vascular smooth muscle cells
Authors: Lee Hye Sun , Yun Sung Ji , Ha Jung Min , Jin Seo Yeon , Ha Hong Koo , Song Sang Heon , Kim Chi Dae , Bae Sun Sik 
Published: November 2019

AbstractSince chronic inflammation is associated with the pathogenesis of atherosclerosis, inflammatory cytokines might contribute to the phenotypic modulation of vascular smooth muscle cells (VSMCs). Tumor necrosis factor α (TNFα) facilitated the transformation of contractile VSMCs to the synthetic phenotype, as determined by the expression of marker proteins and a collagen gel contraction assay. Western blot analysis and a cyclooxygenase-2 (COX2) promoter assay revealed that TNFα stimulation resulted in the induction of COX2. The overexpression, silencing, or pharmacological inhibition of COX2 significantly affected TNFα-induced phenotypic conversion, and of the tested prostaglandins, only PGD2significantly induced phenotypic conversion. ERK was significantly activated by PGD2stimulation, and the pharmacological inhibition of ERK blocked the PGD2-induced phenotypic conversion of VSMCs. However, antagonists or agonists of PGD2receptors did not affect VSMC conversion. In contrast, spontaneously dehydrated forms of PGD2, such as PGJ2, Δ12-PGJ2, and 15-d-PGJ2, strongly induced phenotypic conversion. A reporter gene assay showed that TNFα, PGD2, and 15-d-PGJ2significantly activated the peroxisome proliferator-responsive element (PPRE) promoter. In addition, the overexpression or silencing of peroxisome proliferator-activated receptor δ (PPARδ) significantly influenced 15-d-PGJ2-induced phenotypic conversion. Finally, atherosclerotic neointima formation was significantly suppressed in mice lacking TNFα. In addition, mice fed celecoxib exhibited complete inhibition of carotid artery ligation-induced neointima formation. This study shows that PGD2regulates the phenotypic conversion of VSMCs by generating an endogenous ligand of PPAR, and that this leads to neointima formation in occlusive arterial disease.
Boosting therapeutic potency of antibodies by taming Fc domain functions
Authors: Kang Tae Hyun , Jung Sang Taek 
Published: November 2019

AbstractMonoclonal antibodies (mAbs) are one of the most widely used drug platforms for infectious diseases or cancer therapeutics because they selectively target pathogens, infectious cells, cancerous cells, and even immune cells. In this way, they mediate the elimination of target molecules and cells with fewer side effects than other therapeutic modalities. In particular, cancer therapeutic mAbs can recognize cell-surface proteins on target cells and then kill the targeted cells by multiple mechanisms that are dependent upon a fragment crystallizable (Fc) domain interacting with effector Fc gamma receptors, including antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated phagocytosis. Extensive engineering efforts have been made toward tuning Fc functions by either reinforcing (e.g. for targeted therapy) or disabling (e.g. for immune checkpoint blockade therapy) effector functions and prolonging the serum half-lives of antibodies, as necessary. In this report, we review Fc engineering efforts to improve therapeutic potency, and propose future antibody engineering directions that can fulfill unmet medical needs.
Microplasma direct writing for site-selective surface functionalization of carbon microelectrodes
Authors: Thiha Aung , Ibrahim Fatimah , Muniandy Shalini , Madou Marc J. 
Published: November 2019

AbstractCarbon micro- and nanoelectrodes fabricated by carbon microelectromechanical systems (carbon MEMS) are increasingly used in various biosensors and supercapacitor applications. Surface modification of as-produced carbon electrodes with oxygen functional groups is sometimes necessary for biofunctionalization or to improve electrochemical properties. However, conventional surface treatment methods have a limited ability for selective targeting of parts of a surface area for surface modification without using complex photoresist masks. Here, we report microplasma direct writing as a simple, low-cost, and low-power technique for site-selective plasma patterning of carbon MEMS electrodes with oxygen functionalities. In microplasma direct writing, a high-voltage source generates a microplasma discharge between a microelectrode tip and a target surface held at atmospheric pressure. In our setup, water vapor acts as an ionic precursor for the carboxylation and hydroxylation of carbon surface atoms. Plasma direct writing increases the oxygen content of an SU-8-derived pyrolytic carbon surface from ~3 to 27% while reducing the carbon-to-oxygen ratio from 35 to 2.75. Specifically, a microplasma treatment increases the number of carbonyl, carboxylic, and hydroxyl functional groups with the largest increase observed for carboxylic functionalities. Furthermore, water microplasma direct writing improves the hydrophilicity and the electrochemical performance of carbon electrodes with a contact-angle change from ~90° to ~20°, a reduction in the anodic peak to cathodic peak separation from 0.5 V to 0.17 V, and a 5-fold increase in specific capacitance from 8.82 mF∙cm−2 to 46.64 mF∙cm−2. The plasma direct-writing technology provides an efficient and easy-to-implement method for the selective surface functionalization of carbon MEMS electrodes for electrochemical and biosensor applications.
MicroRNA mediators of early life stress vulnerability to depression and suicidal behavior
Authors: Allen Lauren , Dwivedi Yogesh 
Published: November 2019

AbstractChildhood environment can have a profound impact on brain structure and function. Epigenetic mechanisms have been shown to play a critical role in adaptive and maladaptive processes by regulating gene expression without changing the genome. Over the past few years, early life stress (ELS) has been established as a major risk factor for major depression and suicidal behavior along with other psychiatric illnesses in adulthood. In recent years, the emergence of small noncoding RNAs as a mega controller of gene expression has gained attention for their role in various disease processes. Among various noncoding RNAs, microRNAs (miRNAs) are the most studied and well characterized and have emerged as a major regulator of neural plasticity and higher brain functioning. More recently, although limited in number, studies are focusing on how miRNAs can play a role in the maladaptive processes associated with ELS both at adolescent and adult age and whether these processes are critical in developing depression and suicidal behavior. In this review, we critically evaluate how postnatal ELS relates to abnormalities in miRNA expression and functions from both animal and human literature and draw connections from these findings to depression and suicidal behavior later in life.
A regulatory variant of CHRM3 is associated with cannabis-induced hallucinations in European Americans
Authors: Cheng Zhongshan , Phokaew Chureerat , Chou Yi-Ling , Lai Dongbing , Meyers Jacquelyn L. , Agrawal Arpana , Farrer Lindsay A. , Kranzler Henry R. , Gelernter Joel 
Published: November 2019

AbstractCannabis, the most widely used illicit drug, can induce hallucinations. Our understanding of the biology of cannabis-induced hallucinations (Ca-HL) is limited. We used the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) to identify cannabis-induced hallucinations (Ca-HL) among long-term cannabis users (used cannabis ≥1 year and ≥100 times). A genome-wide association study (GWAS) was conducted by analyzing European Americans (EAs) and African Americans (AAs) in Yale-Penn 1 and 2 cohorts individually, then meta-analyzing the two cohorts within population. In the meta-analysis of Yale-Penn EAs (n = 1917), one genome-wide significant (GWS) signal emerged at the CHRM3 locus, represented by rs115455482 (P = 1.66 × 10−10), rs74722579 (P = 2.81 × 10−9), and rs1938228 (P = 1.57 × 10−8); signals were GWS in Yale-Penn 1 EAs (n = 1092) and nominally significant in Yale-Penn 2 EAs (n = 825). Two SNPs, rs115455482 and rs74722579, were available from the Collaborative Study on the Genetics of Alcoholism data (COGA; 3630 long-term cannabis users). The signals did not replicate, but when meta-analyzing Yale-Penn and COGA EAs, the two SNPs’ association signals were increased (meta-P-values 1.32 × 10−10 and 2.60 × 10−9, respectively; n = 4291). There were no significant findings in AAs, but in the AA meta-analysis (n = 3624), nominal significance was seen for rs74722579. The rs115455482*T risk allele was associated with lower CHRM3 expression in the thalamus. CHRM3 was co-expressed with three psychosis risk genes (GABAG2, CHRNA4, and HRH3) in the thalamus and other human brain tissues and mouse GABAergic neurons. This work provides strong evidence for the association of CHRM3 with Ca-HL and provides insight into the potential involvement of thalamus for this trait.
Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics
Authors: Ruso-Julve Fulgencio , Pombero Ana , Pilar-Cuéllar Fuencisla , García-Díaz Nuria , Garcia-Lopez Raquel , Juncal-Ruiz María , Castro Elena , Díaz Álvaro , Vazquez-Bourgón Javier , García-Blanco Agustín , Garro-Martinez Emilio , Pisonero Helena , Estirado Alicia , Ayesa-Arriola Rosa , López-Giménez Juan , Mayor Federico , Valdizán Elsa , Meana Javier , Gonzalez-Maeso Javier , Martínez Salvador , Vaqué José Pedro , Crespo-Facorro Benedicto 
Published: November 2019

AbstractA better understanding of the molecular mechanisms that participate in the development and clinical manifestations of schizophrenia can lead to improve our ability to diagnose and treat this disease. Previous data strongly associated the levels of deregulated ADAMTS2 expression in peripheral blood mononuclear cells (PBMCs) from patients at first episode of psychosis (up) as well as in clinical responders to treatment with antipsychotic drugs (down). In this current work, we performed an independent validation of such data and studied the mechanisms implicated in the control of ADAMTS2 gene expression. Using a new cohort of drug-naïve schizophrenia patients with clinical follow-up, we confirmed that the expression of ADAMTS2 was highly upregulated in PBMCs at the onset (drug-naïve patients) and downregulated, in clinical responders, after treatment with antipsychotics. Mechanistically, ADAMTS2 expression was activated by dopaminergic signalling (D1-class receptors) and downstream by cAMP/CREB and mitogen-activated protein kinase (MAPK)/ERK signalling. Incubation with antipsychotic drugs and selective PKA and MEK inhibitors abrogated D1-mediated activation of ADAMTS2 in neuronal-like cells. Thus, D1 receptors signalling towards CREB activation might participate in the onset and clinical responses to therapy in schizophrenia patients, by controlling ADAMTS2 expression and activity. The unbiased investigation of molecular mechanisms triggered by antipsychotic drugs may provide a new landscape of novel targets potentially associated with clinical efficacy.
Modulation of autophagy by RTN-1C: role in autophagosome biogenesis
Authors: D’ Eletto Manuela , Risuglia Anna , Oliverio Serafina , Mehdawy Bisan , Nardacci Roberta , Bordi Matteo , Di Sano Federica 
Published: November 2019

AbstractThe endoplasmic reticulum (ER) is a key organelle fundamental for the maintenance of cellular homeostasis and to determine the cell’s fate under stress conditions. Among the known proteins that regulate ER structure and function there is Reticulon-1C (RTN-1C), a member of the reticulon family localized primarily on the ER membrane. We previously demonstrated that RTN-1C expression affects ER function and stress condition. ER is an essential site for the regulation of apoptotic pathways and it has also been recently recognized as an important component of autophagic signaling. Based on these evidences, we have investigated the impact of RTN-1C modulation on autophagy induction. Interestingly we found that reticulon overexpression is able to activate autophagic machinery and its silencing results in a significative inhibition of both basal and induced autophagic response. Using different experimental approaches we demonstrated that RTN-1C colocalizes with ATG16L and LC3II on the autophagosomes. Considering the key role of reticulon proteins in the control of ER membrane shaping and homeostasis, our data suggest the participation of RTN-1C in the autophagic vesicle biogenesis at the level of the ER compartment. Our data indicate a new mechanism by which this structural ER protein modulates cellular stress, that is at the basis of different autophagy-related pathologies.
Neurons can upregulate Cav-1 to increase intake of endothelial cells-derived extracellular vesicles that attenuate apoptosis via miR-1290
Authors: Yue Kang-Yi , Zhang Pei-Ran , Zheng Min-Hua , Cao Xiu-Li , Cao Yuan , Zhang Yi-Zhe , Zhang Yu-Fei , Wu Hai-Ning , Lu Zhi-Hong , Liang Liang , Jiang Xiao-Fan , Han Hua 
Published: November 2019

AbstractExtracellular vesicles (EVs) including exosomes can serve as mediators of cell–cell communication under physiological and pathological conditions. However, cargo molecules carried by EVs to exert their functions, as well as mechanisms for their regulated release and intake, have been poorly understood. In this study, we examined the effects of endothelial cells-derived EVs on neurons suffering from oxygen-glucose deprivation (OGD), which mimics neuronal ischemia-reperfusion injury in human diseases. In a human umbilical endothelial cell (HUVEC)–neuron coculture assay, we found that HUVECs reduced apoptosis of neurons under OGD, and this effect was compromised by GW4869, a blocker of exosome release. Purified EVs could be internalized by neurons and alleviate neuronal apoptosis under OGD. A miRNA, miR-1290, was highly enriched in HUVECs-derived EVs and was responsible for EV-mediated neuronal protection under OGD. Interestingly, we found that OGD enhanced intake of EVs by neurons cultured in vitro. We examined the expression of several potential receptors for EV intake and found that caveolin-1 (Cav-1) was upregulated in OGD-treated neurons and mice suffering from middle cerebral artery occlusion (MCAO). Knock-down of Cav-1 in neurons reduced EV intake, and canceled EV-mediated neuronal protection under OGD. HUVEC-derived EVs alleviated MCAO-induced neuronal apoptosis in vivo. These findings suggested that ischemia likely upregulates Cav-1 expression in neurons to increase EV intake, which protects neurons by attenuating apoptosis via miR-1290.
Browning of white adipose tissue after a burn injury promotes hepatic steatosis and dysfunction
Authors: Abdullahi Abdikarim , Samadi Osai , Auger Christopher , Kanagalingam Tharsan , Boehning Darren , Bi Sheng , Jeschke Marc G. 
Published: November 2019

AbstractBurn patients experiencing hypermetabolism develop hepatic steatosis, which is associated with liver failure and poor outcomes after the injury. These same patients also undergo white adipose tissue (WAT) browning, which has been implicated in mediating post-burn cachexia and sustained hypermetabolism. Despite the clinical presentation of hepatic steatosis and WAT browning in burns, whether or not these two pathological responses are linked remains poorly understood. Here, we show that the burn-induced WAT browning and its associated increased lipolysis leads to the accelerated development of hepatic steatosis in mice. Deletion of interleukin 6 (IL-6) and the uncoupling protein 1 (UCP1), regulators of burn-induced WAT browning completely protected mice from hepatic steatosis after the injury. Treatment of post-burn mice with propranolol or IL-6 receptor blocker attenuated burn-induced WAT browning and its associated hepatic steatosis pathology. Lipidomic profiling in the plasma of post-burn mice and burn patients revealed elevated levels of damage-inducing lipids (palmitic and stearic acids), which induced hepatic endoplasmic reticulum (ER) stress and compromised hepatic fat oxidation. Mechanistically, we show that hepatic ER stress after a burn injury leads to a greater ER-mitochondria interaction, hepatocyte apoptosis, oxidative stress, and impaired fat oxidation. Collectively, our findings uncover an adverse “cross-talk” between the adipose and liver tissue in the context of burn injury, which is critically mediated by WAT browning.
Hyperactivity of Mek in TNS1 knockouts leads to potential treatments for cystic kidney diseases
Authors: Wu Zong-Ye , Chiu Chun-Lung , Lo Ethan , Lee Yuh-Ru Julie , Yamada Soichiro , Lo Su Hao 
Published: November 2019

AbstractCystic kidney disease is the progressive development of multiple fluid-filled cysts that may severely compromise kidney functions and lead to renal failure. TNS1 (tensin-1) knockout mice develop cystic kidneys and die from renal failure. Here, we have established TNS1-knockout MDCK cells and applied 3D culture system to investigate the mechanism leading to cyst formation. Unlike wild-type MDCK cells, which form cysts with a single lumen, TNS1-knockout cysts contain multiple lumens and upregulated Mek/Erk activities. The multiple lumen phenotype and Mek/Erk hyperactivities are rescued by re-expression of wild-type TNS1 but not the TNS1 mutant lacking a fragment essential for its cell–cell junction localization. Furthermore, Mek inhibitor treatments restore the multiple lumens back to single lumen cysts. Mek/Erk hyperactivities are also detected in TNS1-knockout mouse kidneys. Treatment with the Mek inhibitor trametinib significantly reduces the levels of interstitial infiltrates, fibrosis and dilated tubules in TNS1-knockout kidneys. These studies establish a critical role of subcellular localization of TNS1 in suppressing Mek/Erk signaling and maintaining lumenogenesis, and provide potential therapeutic strategies by targeting the Mek/Erk pathway for cystic kidney diseases.
Quorum sensing modulates the formation of virulent Legionella persisters within infected cells
Authors: Personnic Nicolas , Striednig Bianca , Lezan Emmanuelle , Manske Christian , Welin Amanda , Schmidt Alexander , Hilbi Hubert 
Published: November 2019

AbstractThe facultative intracellular bacterium Legionella pneumophila replicates in environmental amoebae and in lung macrophages, and causes Legionnaires’ disease. Here we show that L. pneumophila reversibly forms replicating and nonreplicating subpopulations of similar size within amoebae. The nonreplicating bacteria are viable and metabolically active, display increased antibiotic tolerance and a distinct proteome, and show high virulence as well as the capacity to form a degradation-resistant compartment. Upon infection of naïve or interferon-γ-activated macrophages, the nonreplicating subpopulation comprises ca. 10% or 50%, respectively, of the total intracellular bacteria; hence, the nonreplicating subpopulation is of similar size in amoebae and activated macrophages. The numbers of nonreplicating bacteria within amoebae are reduced in the absence of the autoinducer synthase LqsA or other components of the Lqs quorum-sensing system. Our results indicate that virulent, antibiotic-tolerant subpopulations of L. pneumophila are formed during infection of evolutionarily distant phagocytes, in a process controlled by the Lqs system.