bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptionally induced enhancers in the macrophage immune response toMycobacterium tuberculosisinfection
Authors: Denisenko Elena , Guler Reto , Mhlanga Musa , Suzuki Harukazu , Brombacher Frank , Schmeier Sebastian 
Published: April 2018

AbstractBackgroundTuberculosis is a life-threatening infectious disease caused byMycobacterium tuberculosis(M.tb).M.tbsubverts host immune responses to build a favourable niche and survive inside of host macrophages. Macrophages can control or eliminate the infection, if appropriate transcriptional programs are activated. The role of transcriptional enhancers in the activation and maintenance of these programs remains unexplored.ResultsWe analysed transcribed enhancers inM.tb-infected mouse bone marrow-derived macrophages. We established a link between knownM.tb-responsive transcription factors and transcriptional activation of enhancers and their target genes. Our data suggest that enhancers might drive the macrophage response via transcriptional activation of key immune genes, such as Tnf, Tnfrsf1b, Irg1, Hilpda, Ccl3, and Ccl4. We report enhancers acquiring transcriptionde novoupon infection. Finally, we link highly transcriptionally induced enhancers to the activation of genes with previously unappreciated roles inM.tbinfection, such as Fbxl3, Tapt1, Edn1, and Hivep1.ConclusionsOur findings extend current knowledge of the regulation of macrophage responses toM.tbinfection and provide a basis for future functional studies on enhancer-gene interactions in this process.
Azithromycin reduces systemic inflammation and provides survival benefit in murine model of polymicrobial sepsis
Authors: Patel Anasuya , Joseph Jiji , Periasamy Hariharan , Mokale Santosh 
Published: April 2018

ABSTRACTSepsis is a life threatening systemic inflammatory condition triggered as a result of excessive host immune response to infection. In the past, drugs modulating immune reactions have demonstrated protective effect in sepsis. Azithromycin (macrolide antibiotic) with immunomodulatory activity was therefore evaluated in combination with ceftriaxone in a more clinically relevant murine model of sepsis induced by caecal ligation and puncture (CLP). First, mice underwent CLP and 3 h later were administered with vehicle, sub-effective dose of ceftriaxone (100 mg/kg,subcutaneous) alone or in combination with immunomodulatory dose of azithromycin (100 mg/kg,intraperitoneal). Survival was then monitored for 5 days. Parameters like body temperature, blood glucose, total white blood cell count, plasma glutathione (GSH), plasma and lung myeloperoxidase (MPO) as well as cytokine (interleukin IL-6, IL-1β, tumor necrosis factor-α) levels along with bacterial load in blood, peritoneal fluid and lung homogenate were measured 18 h after CLP challenge. Combination group significantly improved the survival of CLP mice. It attenuated the elevated levels of inflammatory cytokines and MPO in plasma and lung tissue and increased the body temperature, blood glucose and GSH which were otherwise markedly decreased in CLP mice. Ceftriaxone exhibited significant reduction of bacterial count in blood, peritoneal fluid and lung homogenate, while co-administration of azithromycin did not further reduce it. This confirms that survival benefit by azithromycin was due to immunomodulation and not by its antibacterial action. Findings of this study indicate that azithromycin in combination with ceftriaxone could exhibit clinical benefit in sepsis.
Endothelial cells secreted ET-1 augments DN via inducing EM accumulation of MCs in ETBR−/− mice
Authors: Zou Hong-hong , Wang Li , Shen Yun-feng , Zheng Xiao-xu , Xu Gao-si 
Published: April 2018

AbstractETBR deficiency may contribute to the progression of DN in a STZ model, but the underlying mechanism is not fully revealed. In this study, STZ-diabetic ETBR−/− mice was characterized by increased serum creatinine, urinary albumin and ET-1 expression, and enhanced glomerulosclerosis compared with STZ-diabetic WT mice. HG conditioned media of ETBR−/− endothelial cells promoted MC proliferation and upregulated ECM-related proteins, and ET-1 knockout in endothelial cells or inhibition of ET-1/ETAR in MC suppressed MC proliferation. ET-1 was over-expressed in ETBR−/− endothelial cells and was regulated by NF-kapapB pathway. And ET-1/ETBR suppressed NF-kappaB via eNOS to modulate ET-1 in endothelial cells. Furthermore, ET-1/ETAR promoted RhoA/ROCK pathway in MC, and accelerated MC proliferation and ECM accumulation. In vivo experiments proved ETBR−/− mice inhibited NF-kappaB pathway to ameliorate DN and eNOS mice had similar results. Hence, in HG-exposed ETBR−/− endothelial cells, suppression of ET-1/ETBR activated NF-kappaB pathway via inhibiting eNOS to secrete large amount of ET-1. Due to the communication between endothelial cells and MCs, ET-1/ETAR in MC promoted RhoA/ROCK pathway to accelerate MC proliferation and ECM accumulation.
Effects of protein size, thermodynamic stability, and net charge on cotranslational folding on the ribosome
Authors: Farías-Rico José Arcadio , Selin Frida Ruud , Myronidi Ioanna , Frühauf Marie , Heijne Gunnar von 
Published: April 2018

AbstractDuring the last five decades, studies of protein folding in dilute buffer solutions have produced a rich picture of this complex process. In the cell, however, proteins can start to fold while still attached to the ribosome (cotranslational folding) and it is not yet clear how the ribosome affects the folding of protein domains of different sizes, thermodynamic stabilities, and net charges. Here, by using arrest peptides as force sensors and on-ribosome pulse proteolysis, we provide a comprehensive picture of how the distance from the peptidyl transferase center in the ribosome at which proteins fold correlates with protein size. Moreover, an analysis of a large collection of mutants of theE. coliribosomal protein S6 shows that the force exerted on the nascent chain by protein folding varies linearly with the thermodynamic stability of the folded state, and that the ribosome environment disfavors folding of domains of high net-negative charge.
Gene regulatory network reconstruction incorporating 3D chromosomal architecture reveals key transcription factors and DNA elements driving neural lineage commitment
Authors: Malysheva Valeriya , Mendoza-Parra Marco Antonio , Blum Matthias , Spivakov Mikhail , Gronemeyer Hinrich 
Published: April 2018

AbstractLineage commitment is a fundamental process that enables the morphogenesis of multicellular organisms from a single pluripotent cell. While many genes involved in the commitment to specific lineages are known, the logic of their joint action is incompletely understood, and predicting the effects of genetic perturbations on lineage commitment is still challenging. Here, we devised a gene regulatory network analysis approach, GRN-loop, to identify key cis-regulatory DNA elements and transcription factors that drive lineage commitment. GRN-loop is based on signal propagation and combines transcription factor binding data with the temporal profiles of gene expression, chromatin state and 3D chromosomal architecture. Applying GRN-loop to a model of morphogen-induced early neural lineage commitment, we discovered a set of driver transcription factors and enhancers, some of them validated in recent data and others hitherto unknown. Our work provides the basis for an integrated understanding of neural lineage commitment, and demonstrates the potential of gene regulatory network analyses informed by 3D chromatin architecture to uncover the key genes and regulatory elements driving developmental processes.
High-resolution experimental and computational electrophysiology reveals weak β-lactam binding events in the porin PorB
Authors: Bartsch Annika , Llabrés Salomé , Pein Florian , Kattner Christof , Schön Markus , Diehn Manuel , Tanabe Mikio , Munk Axel , Zachariae Ulrich , Steinem Claudia 
Published: April 2018

ABSTRACTThe permeation of most antibiotics through the outer membrane of Gram-negative bacteria occurs through porin channels. To design drugs with increased activity against Gram-negative bacteria in the face of the antibiotic resistance crisis, the strict constraints on the physicochemical properties of the permeants imposed by these channels must be better understood. Here we show that a combination of high-resolution electrophysiology, new noise-filtering analysis protocols and atomistic biomolecular simulations reveals weak binding events between the β-lactam antibiotic ampicillin and the porin PorB from the pathogenic bacteriumNeisseria meningitidis. In particular, an asymmetry often seen in the electrophysiological characteristics of ligand-bound channels is utilised to characterise the binding site and molecular interactions in detail, based on the principles of electro-osmotic flow through the channel. Our results provide a rationale for the determinants that govern the binding and permeation of zwitterionic antibiotics in anion-selective porin channels.
Large time step discrete-time modeling of sharp wave activity in hippocampal area CA3
Authors: Malerba Paola , Rulkov Nikolai F. , Bazhenov Maxim 
Published: April 2018

AbstractReduced models of neuronal spiking activity simulated with a fixed integration time step are frequently used in studies of spatio-temporal dynamics of neurobiological networks. The choice of fixed time step integration provides computational simplicity and efficiency, especially in cases dealing with large number of neurons and synapses operating at a different level of activity across the population at any given time. A network model tuned to generate a particular type of oscillations or wave patterns is sensitive to the intrinsic properties of neurons and synapses and, therefore, commonly susceptible to changes in the time step of integration. In this study, we analyzed a model of sharp-wave activity in the network of hippocampal area CA3, to examine how an increase of the integration time step affects network behavior and to propose adjustments of intrinsic properties of neurons and synapses that help minimize or remove the damage caused by the time step increase.HighlightsSpiking models of neural network activity are sensitive to the integration stepLarger integration time steps are preferable in simulating large networksCase study of CA3 sharp waves shows time step increase damages network dynamicsNeuronal and synaptic parameters adjustments rescue the dynamics at large time step1
S-Nitrosylation of STIM1 by neuronal nitric oxide synthase inhibits store-operated Ca2+ entry
Authors: Gui Le , Zhu Jinhui , Lu Xiangru , Sims Stephen M. , Lu Wei-Yang , Stathopulos Peter B. , Feng Qingping 
Published: April 2018

AbstractStore-operated Ca2+ entry (SOCE) mediated by stromal interacting molecule-1 (STIM1) and Orai1 represents a major route of Ca2+ entry in mammalian cells and is initiated by STIM1 oligomerization in the endoplasmic or sarcoplasmic reticulum (ER/SR). However, the effects of nitric oxide (NO) on STIM1 function are unknown. Neuronal NO synthase (nNOS) is located in the SR of cardiomyocytes. Here, we show that STIM1 is susceptible to S-nitrosylation. nNOS deficiency or inhibition enhanced Ca2+ release-activated Ca2+ channel current (ICRAC) and SOCE in cardiomyocytes. Consistently, NO donor S-nitrosoglutathione (GSNO) inhibited STIM1 puncta formation and ICRAC in HEK293 cells, but this effect was absent in cells expressing the Cys49Ser/Cys56Ser STIM1 double mutant. Furthermore, NO donors caused Cys49 and Cys56-specific structural changes associated with reduced protein backbone mobility, increased thermal stability and suppressed Ca2+-depletion-dependent oligomerization of the luminal Ca2+-sensing region of STIM1. Collectively, our data show that S-nitrosylation of STIM1 suppresses oligomerization via enhanced luminal domain stability and rigidity, and inhibits SOCE in cardiomyocytes.
A member of the ferlin calcium sensor family is essential forToxoplasma gondiirhoptry secretion
Authors: Coleman Bradley I. , Saha Sudeshna , Sato Seiko , Engelberg Klemens , Ferguson David J. P. , Coppens Isabelle , Lodoen Melissa B. , Gubbels Marc-Jan 
Published: April 2018

AbstractInvasion of host cells by apicomplexan parasites such asToxoplasma gondiiis critical for their infectivity and pathogenesis. InToxoplasma, secretion of essential egress, motility and invasion-related proteins from microneme organelles is regulated by oscillations of intracellular Ca2+. Later stages of invasion are considered Ca2+-independent, including the secretion of proteins required for host cell entry and remodeling from the parasite’s rhoptries. We identified a family of threeToxoplasmaproteins with homology to the ferlin family of double C2 domain-containing Ca2+sensors. In humans and model organisms such Ca2+sensors orchestrate Ca2+-dependent exocytic membrane fusion with the plasma membrane. One ferlin that is conserved across the Apicomplexa, TgFER2, localizes to the parasite’s cortical membrane skeleton, apical end, and rhoptries. Unexpectedly, conditionally TgFER2-depleted parasites secreted their micronemes normally and were completely motile. However, these parasites were unable to invade host cells and were therefore not viable. Specifically, knockdown of TgFER2 prevented rhoptry secretion and these parasites failed to form the moving junction on the parasite-host interface necessary for host cell invasion. Collectively, these data demonstrate that the putative Ca2+sensor TgFER2 is required for the secretion of rhoptries. These findings provide the first regulatory and mechanistic insights into this critical yet poorly understood aspect of apicomplexan host cell invasion.Graphical abstract
Theta-gamma coupling: a nonlinear dynamical model
Authors: Sheremet Alex , Zhou Yuchen , Kennedy Jack P. , Qin Yu , Burke Sara N. , Maurer Andrew P. 
Published: April 2018

AbstractCross-frequency coupling in the hippocampus has been hypothesized to support higher-cognition functions. While gamma modulation by theta is widely accepted, evidence of phase-coupling between the two frequency components is so far unconvincing. Our observations show that theta and gamma energy increases with rat speed, while the overall nonlinearity of the LFP trace also increases, suggesting that energy flow is fundamental for hippocampal dynamics. This contradicts current representations based on the Kuramoto phase model. Therefore, we propose a new approach, based on the three-wave equation, a universally-valid nonlinear-physics paradigm that synthesizes the effects of leading order, quadratic nonlinearity. The paradigm identifies bispectral analysis as the natural tool for investigating LFP cross-frequency coupling. Our results confirm the effectiveness of the approach by showing unambiguous coupling between theta and gamma. Bispectra features agree with predictions of the three-wave model, supporting the conclusion that cross-frequency coupling is a manifestation of nonlinear energy transfers.
A CuII complex with an carbamoylcyanonitrosomethanide ligand formed in situ by the nucleophilic addition of water to dicyanonitrosomethanide: structure, spectral and magnetic properties
Authors: Potočňák Ivan , Bukrynov Oleksandr , Kliuikov Andrii , Čižmár Erik , Vitushkina Svitlana , Váhovská Lucia , Dušek Michal 
Published: April 2018

The complex (2,2′-biquinoline-κ2
N,N′)(carbamoylcyanonitrosomethanide-κ2
N,O)chloridocopper(II) acetonitrile monosolvate, [Cu(C3H2N3O2)Cl(C18H12N2)]·CH3CN or [Cu(ccnm)Cl(biq)]·acn (acn is acetonitrile, biq is 2,2′-biquinoline and ccnm is carbamoylcyanonitrosomethanide), (I), was prepared as a result of nucleophilic addition of water to the dicyanonitrosomethanide ion in the presence of CuII and biq. IR spectroscopy confirmed the presence of ccnm, biq and acn in (I). The solid-state structure consists of the neutral complex containing ccnm and biq ligands, coordinated to the CuII atom in a bidendate chelating manner, and a chloride ligand, resulting in a distorted tetragonal pyramidal coordination of CuII. The asymmetric unit is supplemented by one molecule of solvated acn which, along with the nitrile group of ccnm, serves as an acceptor in intermolecular hydrogen bonding, creating infinite chains along the b axis. Magnetic measurements revealed a paramagnetic behaviour with a very small Weiss temperature Θ = −0.32 K and high anisotropy of the g tensor (g

x
= 2.036, g

y
= 2.120 and g

z
= 2.205).
Accelerated tax depreciation and farm investment: evidence from Michigan
Authors: Polzin Leonard , Wolf Christopher A. , Black J. Roy 
Published: April 2018

Purpose
The purpose of this paper is to examine the use of accelerated depreciation deductions, which includes Section 179 and bonus depreciation, taken in the first year of asset life by Michigan farms. The frequency, value and influence of accelerated depreciation on farm investment are also analyzed.

Design/methodology/approach
Accrual adjusted income statements, balance sheets, depreciation schedules, and income tax information for 66 Michigan farms from 2004 to 2014 provide data for the analysis. The present value of the accelerated deduction and change in the cost of capital were calculated. Finally, investment elasticities were used to arrive at the change in investment due to accelerated depreciation.

Findings
Accelerated depreciation was utilized across all applicable asset classes. Section 179 was used more often than bonus depreciation in part because it was available in all the examined years. Based on actual farm business use, accelerated depreciation lowered the cost of capital for the operations resulting in an estimated increase in investment of 0.27 to 11.6 percent depending on asset class.

Originality/value
The data utilized are of a detail not available in previous investigations which used either aggregate data or estimated rather than the observed use of accelerated depreciation. This analysis reveals that accelerated depreciation as used by commercial farms lowers the cost of capital and thus encourages investment particularly in machinery and equipment.
Dynamic relationship between Nigeria-US exchange rate and crude oil price
Authors: Raji Jimoh Olajide , Idowu Abdulkadir Rihanat , Badru Bazeet Olayemi 
Published: April 2018

PurposeThe purpose of this paper is to investigate the dynamic relationship between Nigeria-US exchange rate (XR) and crude oil price (OILP) using daily data from 1 January 2001 to 31 December 2015.Design/methodology/approachThe study uses alternative methods, including vector autoregressive-generalised autoregressive conditional heteroskedasticity (VAR-GARCH) within the framework of Baba-Engle-Kraft-Kroner model, constant conditional correlation (CCC)-GARCH and dynamic conditional correlation (DCC)-GARCH models.FindingsThe results from the VAR-GARCH model indicate unidirectional cross-market mean spillovers from oil market (OILM) to foreign exchange market (FXM). In addition, the results show a positive effect of OILP on XR, suggesting that an increase in OILP appreciates Nigerian currency relative to US dollar and a fall in OILP depreciates it. The authors find that the effects of cross-volatility spillovers between the OILM and FXM are bidirectional. The CCC results indicate positive correlations of returns of 16 per cent between the FXM and OILM. Finally, the DCCs results indicate positive correlations between the two markets since the fourth quarter of 2008 (the world financial crisis period) until the recent period of world oil glut and slow demand for crude oil.Research limitations/implicationsFollowing the depreciation of the Nigerian currencyvis-á-visUS dollar since the onset of the recent world oil glut and lower oil prices, Nigerian authorities should embark on subsidy reform, such as reduction in fuel subsidies. This may enable the release of fiscal resources that may be used to either rebuild fiscal space lost or finance investment in non-oil sectors in order to reduce overdependence on oil income. Lower fiscal revenues, coupled with the risk that crude oil maintains its low price for some time, imply that government should reduce its expenditure, and continue to draw on available accumulated funds from the excess crude account for some time until the real depreciation required for adjustment is achieved.Originality/valueStudies on volatility spillovers between OILM and FXM are limited in the literature, particularly in Nigerian case. Moreover, the study employs different approaches for broader analysis. These alternative methods, a clear departure from the previous studies, provide comprehensive dynamic nature of the relationship between the FXM and OILM.
Exploring the long-term trade-off between efficiency and value creation in horizontal M&As
Authors: Akpan Mfon Nathaniel Udo , Aik Nai Chiek , Wanke Peter Fernandes , Chau Wong Hong 
Published: April 2018

Purpose
The purpose of this paper is to investigate the voluntary horizontal M&A impact on operating performance in Nigeria between 1995 and 2012 under different complementary approaches.

Design/methodology/approach
Residual income valuation (RIV), economic value-added (EVA), data envelopment analysis (DEA) and stochastic frontier analysis (SFA).

Findings
Results showed a statistically significant improvement in the technical efficiency of both bidder and target companies, the reduced efficiency levels of the bidder firms under DEA scores reveals the specifics of the productive technology. This may suggest that resulting merged companies in Nigeria may have not even become too big in scale or even reached the most productive scale size, despite their almost monopolistic position in the sector. This happens because the scale size of the sector is small per se, implying that the investments necessary to achieve synergistic gains have to be partially covered by price increases.

Practical implications
This study will guide both the M&A practitioners, investment banks, and the policy makes. In terms of having to review M&A policy as well as seeing to the improvement in the infrastructural needs.

Social implications
With improved performance, employment can be created thereby giving employment to the youths. This will reduce social problems.

Originality/value
From the literature and records, no long-term operating performance on voluntary mergers and acquisitions has not been carried out in Nigeria. The paper seeks to know the fundamental value of the firms after these transactions with the current methodology that is acceptable from the literature.