bluuebunny/crossref_metadata_2025 huggingface dataset:
Ustekinumab – eine Standortbestimmung
Authors: Siegmund Britta , Högenauer Christoph , Novacek Gottfried , Petritsch Wolfgang , Reinisch Walter , Schoepfer Alain , Schreiber Stefan , Vavricka Stephan , Bokemeyer Bernd ,   für die IBD-Dach-Gruppe
Published: August 2018

Die vorliegende Übersicht der IBD-Dach-Gruppe legt eine Übersicht zu Wirkmechanismus, klinischer Entwicklung, Zulassung, Wirksamkeit und Sicherheitsaspekten des neuen Anti-p40-Antikörpers Ustekinumab vor, der für die Therapie des moderaten bis schweren Morbus Crohn zugelassen ist. Die Arbeit fasst die aktuelle Datenlage zusammen und enthält somit sowohl die Daten der Zulassungsstudien als auch die Daten aus kleineren und auch fachübergreifenden Arbeiten, mit denen die Aspekte zu besonderen Situationen diskutiert werden können. Alle Arbeiten zusammen zeigen, dass mit Ustekinumab eine wirksame und sichere Option für den Morbus Crohn zur Verfügung steht.
Endothelial Cells Harbouring the JAK2V617F Mutation Display Pro-Adherent and Pro-Thrombotic Features
Authors: Guadall Anna , Lesteven Elodie , Letort Gil , Awan Toor Sarah , Delord Marc , Pognant Doriane , Brusson Mégane , Verger Emmanuelle , Maslah Nabih , Giraudier Stéphane , Larghero Jerome , Vanneaux Valerie , Chomienne Christine , El Nemer Wassim , Cassinat Bruno , Kiladjian Jean-Jacques
Published: August 2018

Thromboembolic events are the main cause of mortality in BCR-ABL1-negative myeloproliferative neoplasms (MPNs) but their underlying mechanisms are largely unrecognized. The Janus kinase 2 (JAK2)V617F mutation is the most frequent genetic alteration leading to MPN. Usually found in haematopoietic progenitors and stem cells, this mutation has also been described in endothelial cells (ECs) of MPN patients. In this study, we have questioned the impact of the JAK2V617F mutation on EC phenotype and functions. We developed an induced pluripotent stem cells strategy to compare JAK2 mutant and wild-type ECs. Transcriptomic assays showed that several genes and pathways involved in inflammation, cell adhesion and thrombotic events were over-represented in JAK2V617F ECs and expression levels of von Willebrand factor and P-selectin (CD62P) proteins were increased. Finally, we found that leucocytes from MPN patients adhere more tightly to JAK2V617F ECs. Our results show that JAK2V617F ECs have a pro-inflammatory and pro-thrombotic phenotype and were functionally pro-adherent.
Regulation of axon repulsion by MAX-1 SUMOylation and AP-3
Authors: Chen Shih-Yu , Ho Chun-Ta , Liu Wei-Wen , Lucanic Mark , Shih Hsiu-Ming , Huang Pei-Hsin , Cheng Hwai-Jong
Published: August 2018

Significance

During neural development, growing axons navigate over long distances to reach their targets. A critical step in this process is the regulation of its surface receptors on the axon’s growth cone in response to environmental cues. We focus on how the UNC-5 receptor in
Ca
enorhabditis elegans
motor axons is regulated during axon repulsion. By combining
C. elegans
genetics, biochemistry, and imaging, we found that MAX-1 SUMOylation and AP-3 complex have significant roles in UNC-5–mediated axon repulsion. Our findings reveal how SUMOylation and AP-3–mediated trafficking and degradation interact to help the growing axon find its final target.
How children come to understand false beliefs: A shared intentionality account
Authors: Tomasello Michael
Published: August 2018

Significance

In coming to understand minds, the greatest challenge for young children is understanding when others have a false belief. Why is that person searching for the toy over there when it is really over here? There is currently much controversy about when children come to this understanding because experiments of different types yield different results. This paper attempts to resolve the controversy by integrating theory and data in a different way. Specifically, the paper argues that young children do not just come to imagine what is in other minds on their own; rather, they come to this understanding through certain types of social and communicative interactions with others that require them to compare their respective perspectives.
Distinct fNIRS-Derived HbO2 Trajectories During the Course and Over Repeated Walking Trials Under Single- and Dual-Task Conditions: Implications for Within Session Learning and Prefrontal Cortex Efficiency in Older Adults
Authors: Holtzer Roee , Izzetoglu Meltem , Chen Michelle , Wang Cuiling
Published: August 2018

Background

Neural trajectories of gait are not well established. We determined two distinct, clinically relevant neural trajectories, operationalized via functional near-infrared spectroscopy (fNIRS) HbO2 measures in the prefrontal cortex (PFC), under Single-Task-Walk (STW), and Dual-Task-Walk (DTW) conditions. Course trajectory assessed neural activity associated with attention during the course of a walking task; the second trajectory assessed neural activity associated with learning over repeated walking trials. Improved neural efficiency was defined as reduced PFC HbO2 after practice.

Methods

Walking was assessed under STW and DTW conditions. fNIRS was utilized to quantify HbO2 in the PFC while walking. Burst measurement included three repeated trials for each experimental condition. The course of each walking task consisted of six consecutive segments.

Results

Eighty-three nondemented participants (mean age = 78.05 ± 6.37 years; %female = 49.5) were included. Stride velocity (estimate = −0.5259 cm/s, p = <.0001) and the rate of correct letter generation (log estimate of rate ratio = −0.0377, p < .0001) declined during the course of DTW. In contrast, stride velocity (estimate = 1.4577 cm/s, p < .0001) and the rate of correct letter generation (log estimate of rate ratio = 0.0578, p < .0001) improved over repeated DTW trials. Course and trial effects were not significant in STW. HbO2 increased during the course of DTW (estimate = 0.0454 μM, p < .0001) but declined over repeated trials (estimate = −0.1786 μM, p < .0001). HbO2 declined during the course of STW (estimate = −.0542 μM, p < .0001) but did not change significantly over repeated trials.

Conclusion

We provided evidence for distinct attention (course) and learning (repeated trials) trajectories and their corresponding PFC activity. Findings suggest that learning and improved PFC efficiency were demonstrated in one experimental session involving repeated DTW trials.
Debunking Millar v. Taylor: The History of the Prohibition of Legislative History
Authors: Magyar John J
Published: August 2018

The generally accepted belief about the rule prohibiting recourse to legislative history as an aid to statutory interpretation is that it began in the case of Millar v.Taylor in 1769, and it was followed thereafter in England and throughout the United States through to the 20th century. However, all four judges on the panel in Millar v.Taylor considered evidence from the Journal of the House of Commons and changes made to the relevant bill in their opinions. Meanwhile, the case was widely cited for several substantive and procedural matters throughout the 19th century, but it was not cited by a judge as a precedent for the rule against legislative history until 1887. A careful examination of the relevant cases and secondary literature from the 18th and 19th centuries reveals a much more nuanced and complex history to the rule. Its emergence becomes less clear because it is shrouded in judicial silence. Its beginnings must be inferred from a general and often unarticulated principle that lawyers felt free to disregard. Furthermore, the development, refinement, and decline of the rule followed a different timeline in England, the US federal courts and the state courts.
Matrix stiffness regulates vascular integrity through focal adhesion kinase activity
Authors: Wang Wenjun , Lollis Emmanuel M. , Bordeleau François , Reinhart-King Cynthia A.
Published: August 2018

Tumor vasculature is known to be more permeable than the vasculature found in healthy tissue, which in turn can lead to a more aggressive tumor phenotype and impair drug delivery into tumors. While the stiffening of the stroma surrounding solid tumors has been reported to increase vascular permeability, the mechanism of this process remains unclear. Here, we utilize an in vitro model of tumor stiffening, ex ovo culture, and a mouse model to investigate the molecular mechanism by which matrix stiffening alters endothelial barrier function. Our data indicate that the increased endothelial permeability caused by heightened matrix stiffness can be prevented by pharmaceutical inhibition of focal adhesion kinase (FAK) both in vitro and ex ovo. Matrix stiffness‐mediated FAK activation determines Src localization to cell‐cell junctions, which then induces increased vascular endothelial Cadherin phosphorylation both in vitro and in vivo. Endothelial cells in stiff tumors have more activated Src and higher levels of phosphorylated vascular endothelial Cadherin at adherens junctions compared to endothelial cells in more compliant tumors. Altogether, our data indicate that matrix stiffness regulates endothelial barrier integrity through FAK activity, providing one mechanism by which extracellular matrix stiffness regulates endothelial barrier function. Additionally, our work also provides further evidence that FAK is a promising potential target for cancer therapy because FAK plays a critical role in the regulation of endothelial barrier integrity.—Wang, W., Lollis, E. M., Bordeleau, F., Reinhart‐King, C. A. Matrix stiffness regulates vascular integrity through focal adhesion kinase activity. FASEB J. 33, 1199–1208 (2019). www.fasebj.org
Feedback between membrane tension, lipid shape and curvature in the formation of packing defects
Authors: Pinot M. , Vanni S. , Ambroggio E. , Guet D. , Goud B. , Manneville J.-B.
Published: August 2018

Lipid packing defects favor the binding of proteins to cellular membranes by creating spaces between lipid head groups that allow the insertion of amphipathic helices or lipid modifications. The density of packing defects in a lipid membrane is well known to increase with membrane curvature and in the presence of conical-shaped lipids. In contrast, the role of membrane tension in the formation of lipid packing defects has been poorly investigated. Here we use a combination of numerical simulations and experiments to measure the effect of membrane tension on the density of lipid packing defects. We first monitor the binding of ALPS (amphipathic lipid packing sensor) to giant unilamellar vesicles and observe a striking periodic binding of ALPS that we attribute to osmotically-induced membrane tension and transient membrane pore formation. Using micropipette aspiration experiments, we show that a high membrane tension induces a reversible increase in the density of lipid packing defects. We next focus on packing defects induced by lipid shape and show that conical lipids generate packing defects similar to that induced by membrane tension and enhance membrane deformation due to the insertion of the ALPS helix. Both cyclic ALPS binding and the cooperative effect of ALPS binding and conical lipids on membrane deformation result from an interplay between helix insertion and lipid packing defects created by membrane tension, conical lipids and/or membrane curvature. We propose that feedback mechanisms involving membrane tension, lipid shape and membrane curvature play a crucial role in membrane deformation and intracellular transport events.
Role of sciatic nerve stiffness in surgical decision making and follow up in patients with deep gluteal syndrome
Authors: Stajic Sava , Vojvodic Aleksandar , Carro Luis Perez , Mihailovic Jelena , Gasic Milos , Lukic Gordana
Published: August 2018

The study shows the relevance of sciatic nerve stiffness assessed by strain elastography using ARFI (Acoustic Radiation Force Impulse) for surgical decision making and the follow up of patients with deep gluteal syndrome (DGS). The research focuses on nerve stiffness associated with knee movements in order to determine the degree of nerve entrapment. Neurological examination, MRI of pelvis and electromyography (EMG) were performed as well. The sciatic nerve was scanned by ARFI (strain) elastography during knee movements in patients with DGS (143). In 54 patients surgical treatment was indicated, while 24 of them underwent surgery. The results were based on tissue response to ARFI by color elastogram and stiffness ratio. Diameters of the sciatic nerve in patients with DGS during knee flexion were statistically significantly lower than during extension movement (p<0.01). In patients with DGS (in ones without indication and the ones scheduled for surgery) sciatic nerve stiffness ratio was significantly increased (p<0.01) during knee flexion. Patients scheduled for surgery confirmed increased sciatic nerve stiffness during knee movements, compared with those without indications for surgery (p<0.05). Sciatic nerve recovery after surgery by diameter and stiffness ratio was marked (r=0.881). The correlation between MRI and EMG findings and ARFI nerve stiffness values in patients scheduled for surgery was high (r=0.963). The overall specificity of method was 93.5%, sensitivity was 88.9% with accuracy of 90.6%. ARFI elastography (by strain) is a diagnostic procedure based on nerve stiffness assessment and a useful tool in decision making for surgery and the follow up.
Cancer cell CCR2 orchestrates suppression of the adaptive immune response
Authors: Fein Miriam R. , He Xue-Yan , Almeida Ana S. , Bružas Emilis , Pommier Arnaud , Yan Ran , Eberhardt Anaïs , Fearon Douglas T. , Van Aelst Linda , Wilkinson John Erby , dos Santos Camila O. , Egeblad Mikala
Published: August 2018

C-C chemokine receptor type 2 (CCR2) is expressed on monocytes and facilitates their recruitment to tumors. Though breast cancer cells also express CCR2, its functions in these cells are unclear. We found thatCcr2deletion in cancer cells led to reduced tumor growth and ∼2-fold longer survival in an orthotopic, isograft breast cancer mouse model. Deletion ofCcr2in cancer cells resulted in multiple alterations associated with better immune control: increased infiltration and activation of cytotoxic T lymphocytes (CTLs) and CD103+ cross-presenting dendritic cells (DCs), as well as upregulation of MHC class I and downregulation of checkpoint regulator PD-L1 on the cancer cells. Pharmacological or genetic targeting of CCR2 increased cancer cell sensitivity to CTLs and enabled the cancer cells to induce DC maturation toward the CD103+ subtype. Consistently,Ccr2−/−cancer cells did not induce immune suppression inBatf3−/−mice lacking CD103+ DCs. Our results establish that CCR2 signaling in cancer cells can orchestrate suppression of the immune response.

C-C chemokine receptor type 2 (CCR2) expressed on monocytes facilitates their recruitment to tumors. Here, CCR2 signaling in cancer cells is shown to suppress immune control of tumors, in part by reducing CD103+ dendritic cell recruitment.
A New Clustering and Nomenclature for Beta Turns Derived from High-Resolution Protein Structures
Authors: Shapovalov Maxim , Vucetic Slobodan , Dunbrack Roland L.
Published: August 2018

Protein loops connect regular secondary structures and contain 4-residue beta turns which represent 63% of the residues in loops. The commonly used classification of beta turns (Type I, I’, II, II’, VIa1, VIa2, VIb, and VIII) was developed in the 1970s and 1980s from analysis of a small number of proteins of average resolution, and represents only two thirds of beta turns observed in proteins (with a generic class Type IV representing the rest). We present a new clustering of beta turn conformations from a set of 13,030 turns from 1078 ultra-high resolution protein structures (≤1.2 Å). Our clustering is derived from applying the DBSCAN andk-medoids algorithms to this data set with a metric commonly used in directional statistics applied to the set of dihedral angles from the second and third residues of each turn. We define 18 turn types compared to the 8 classical turn types in common use. We propose a new 2-letter nomenclature for all 18 beta-turn types using Ramachandran region names for the two central residues (e.g., ‘A’ and ‘D’ for alpha regions on the left side of the Ramachandran map and ‘a’ and ‘d’ for equivalent regions on the right-hand side; classical Type I turns are ‘AD’ turns and Type I’ turns are ‘ad’). We identify 11 new types of beta turn, 5 of which are sub-types of classical beta turn types. Up-to-date statistics, probability densities of conformations, and sequence profiles of beta turns in loops were collected and analyzed. A library of turn types,BetaTurnLib18, and cross-platform software,BetaTurnTool18, which identifies turns in an input protein structure, are freely available and redistributable fromdunbrack.fccc.edu/betaturnandgithub.com/sh-maxim/BetaTurn18. Given the ubiquitous nature of beta turns, this comprehensive study updates understanding of beta turns and should also provide useful tools for protein structure determination, refinement, and prediction programs.
The capsule ofCryptococcus neoformansmodulates phagosomal pH through its acid-base properties
Authors: De Leon-Rodriguez Carlos M. , Fu Man Shun , Corbali M. Osman , Cordero Radames J.B. , Casadevall Arturo
Published: August 2018

Phagosomal acidification is a critical cellular mechanism for the inhibition and killing of ingested microbes by phagocytic cells. The acidic environment activates microbicidal proteins and creates an unfavorable environment for the growth of many microbes. Consequently, numerous pathogenic microbes have developed strategies for countering phagosomal acidification through various mechanisms that include interference with phagosome maturation. The human pathogenic fungusCryptococcus neoformansresides in acidic phagosome after macrophage ingestion that actually provides a favorable environment for replication since the fungus replicates faster at acidic pH. We hypothesized that the glucuronic acid residues in the capsular polysaccharide had the capacity to affect phagosome acidity through their acid-base properties. A ratiometric fluorescence comparison of imaged phagosomes containingC. neoformansto those containing beads showed that the latter were significantly more acidic. Similarly, phagosomes containing non-encapsulatedC. neoformanscells were more acidic than those containing encapsulated cells. Acid-base titrations of isolatedC. neoformanspolysaccharide revealed that it behaves as a weak acid with maximal buffering capacity around pH 4-5. We interpret these results as indicating that the glucuronic acid residues in theC. neoformanscapsular polysaccharide can buffer phagosomal acidification. Interference with phagosomal acidification represents a new function for the cryptococcal capsule in virulence and suggests the importance of considering the acid-base properties of microbial capsules in the host-microbe interaction for other microbes with charged residues in their capsules.

Importance

Cryptococcus neoformansis the causative agent of cryptococcosis, a devastating fungal disease that affects thousands of individuals worldwide. This fungus has the capacity to survive inside phagocytic cells, which contributes to persistence of infection and dissemination. One of the major mechanisms of host phagocytes is to acidify the phagosomal compartment after ingestion of microbes. This study shows that the capsule ofC. neoformanscan interfere with full phagosomal acidification by serving as a buffer.
“Visual” Cortices of Congenitally Blind Adults Respond to Executive Demands Authors
Authors: Loiotile Rita E. , Bedny Marina
Published: August 2018

How functionally flexible is human cortex? In congenitally blind individuals, “visual” cortices are active during auditory and tactile tasks. The cognitive role of these responses and the underlying mechanisms remain uncertain. A dominant view is that, in blindness, “visual” cortices process information from low-level auditory and somatosensory systems. An alternative hypothesis is that higher-cognitive fronto-parietal systems take over “visual” cortices. We report that, in congenitally blind individuals, right-lateralized “visual” cortex responds to executiveload in a go/no-go task. These right-lateralized occipital cortices of blind, but not sighted, individuals mirrored the executive-function pattern observed in fronto-parietal systems. In blindness, the same “visual” cortex area, at rest, also increases its synchronization with prefrontal executive control regions and decreases its synchronization with auditory and sensorimotor cortices. These results support the hypothesis of top-down fronto-parietal takeover of “visual” cortices, and suggest that human cortex is highly flexible at birth.
Development of novel lipidic particles for siRNA delivery that are highly effective after 12 months storage
Authors: Clarke Daniel , Idris Adi , McMillan Nigel AJ
Published: August 2018

Liposomes are versatile and well-proven as a means to deliver nucleic acids into cells. Most of the formulation procedures used are labour intensive and result in unstable end products. We have previously reported on the development of a simple, yet efficient, hydration-of-freeze-dried-matrix (HFDM) method to entrap siRNA within lipid particles. Here we show that the particles are stable up to 12 months after storage room temperature (RT), 4°C or - 20°C. While RT storage results in changes in particle size and polydispersity, gene silencing of all particles was similar to freshly prepared particles following storage for 3, 6, 9 or 12 months at all temperatures. This is the first report of such long-term stability in siRNA-loaded liposomes.
Real-time structural dynamics of late steps in bacterial translation initiation visualized using time-resolved cryogenic electron microscopy
Authors: Kaledhonkar Sandip , Fu Ziao , Caban Kelvin , Li Wen , Chen Bo , Sun Ming , Gonzalez Ruben L. , Frank Joachim
Published: August 2018

Bacterial translation initiation entails the tightly regulated joining of the 50S ribosomal subunit to an initiator transfer RNA (fMet-tRNAfMet)-containing 30S ribosomal initiation complex (IC) to form a 70S IC that subsequently matures into a 70S elongation-competent complex (70S EC). Rapid and accurate 70S IC formation is promoted by 30S IC-bound initiation factor (IF) 1 and the guanosine triphosphatase (GTPase) IF2, both of which must ultimately dissociate from the 70S IC before the resulting 70S EC can begin translation elongation1. Although comparison of 30S2–6 and 70S5,7–9 IC structures have revealed that the ribosome, IFs, and fMet-tRNAfMet can acquire different conformations in these complexes, the timing of conformational changes during 70S IC formation, structures of any intermediates formed during these rearrangements, and contributions that these dynamics might make to the mechanism and regulation of initiation remain unknown. Moreover, lack of an authentic 70S EC structure has precluded an understanding of ribosome, IF, and fMet-tRNAfMet rearrangements that occur upon maturation of a 70S IC into a 70S EC. Using time-resolved cryogenic electron microscopy (TR cryo-EM)10 we report the first, near-atomic-resolution view of how a time-ordered series of conformational changes drive and regulate subunit joining, IF dissociation, and fMet-tRNAfMet positioning during 70S EC formation. We have found that, within ~20–80 ms, rearrangements of the 30S subunit and IF2, uniquely captured in its GDP•Pi-bound state, stabilize fMet-tRNAfMet in its intermediate, ‘70S P/I’, configuration7 and trigger dissociation of IF1 from the 70S IC. Within the next several hundreds of ms, dissociation of IF2 from the 70S IC is coupled to further remodeling of the ribosome that positions fMet-tRNAfMet into its final, ‘P/P’, configuration within the 70S EC. Our results demonstrate the power of TR cryo-EM to determine how a time-ordered series of conformational changes contribute to the mechanism and regulation of one of the most fundamental processes in biology.
Pleotropic effects of mutations in the effector domain of influenza A virus NS1 protein
Authors: Pereira Carina F. , Wise Helen M. , Kurian Dominic , Pinto Rute M. , Amorim Maria J. , Gill Andrew C. , Digard Paul
Published: August 2018

Objective

The multifunctional NS1 protein of influenza A virus has roles in antagonising cellular innate immune responses and promoting viral gene expression. To better understand the interplay between these functions, we tested the effects of NS1 effector domain mutations known to affect homo-dimerisation or interactions with cellular PI3 kinase or Trim25 on NS1 ability to promote nuclear export of viral mRNAs.

Results

The NS1 dimerisation mutant W187R retained the functions of binding cellular NXF1 as well as stabilising NXF1 interaction with viral segment 7 mRNAs and promoting their nuclear export. Two PI3K-binding mutants, NS1 Y89F and Y89A still bound NXF1 but no longer promoted NXF1 interactions with segment 7 mRNA or its nuclear export. The Trim25-binding mutant NS1 E96A/E97A bound NXF1 and supported NXF1 interactions with segment 7 mRNA but no longer supported mRNA nuclear export. Analysis of WT and mutant NS1 interaction partners identified hsp70 as specifically binding to NS1 E96A/E97A. Whilst these data suggest the possibility of functional links between NS1’s effects on intracellular signalling and its role in viral mRNA nuclear export, they also indicate potential pleiotropic effects of the NS1 mutations; in the case of E96A/E97A possibly via disrupted protein folding leading to chaperone recruitment.
The administration of high-mobility group box 1 fragment prevents deterioration of cardiac performance by enhancement of bone marrow mesenchymal stem cell homing in the delta-sarcoglycan-deficient hamster
Authors: Kido Takashi , Miyagawa Shigeru , Goto Takasumi , Tamai Katsuto , Ueno Takayoshi , Toda Koichi , Kuratani Toru , Sawa Yoshiki
Published: August 2018

Objectives

We hypothesized that systemic administration of high-mobility group box 1 fragment attenuates the progression of myocardial fibrosis and cardiac dysfunction in a hamster model of dilated cardiomyopathy by recruiting bone marrow mesenchymal stem cells thus causing enhancement of a self-regeneration system.

Methods

Twenty-week-old J2N-k hamsters, which are δ-sarcoglycan-deficient, were treated with systemic injection of high-mobility group box 1 fragment (HMGB1, n=15) or phosphate buffered saline (control, n=11). Echocardiography for left ventricular function, cardiac histology, and molecular biology were analyzed. The life-prolonging effect was assessed separately using the HMGB1 and control groups, in addition to a monthly HMGB1 group which received monthly systemic injections of high-mobility group box 1 fragment, 3 times (HMGB1, n=11, control, n=9, monthly HMGB1, n=9).

Results

The HMGB1 group showed improved left ventricular ejection fraction, reduced myocardial fibrosis, and increased capillary density. The number of platelet-derived growth factor receptor-alpha and CD106 positive mesenchymal stem cells detected in the myocardium was significantly increased, and intra-myocardial expression of tumor necrosis factor α stimulating gene 6, hepatic growth factor, and vascular endothelial growth factor were significantly upregulated after high-mobility group box 1 fragment administration. Improved survival was observed in the monthly HMGB1 group compared with the control group.

Conclusions

Systemic high-mobility group box 1 fragment administration attenuates the progression of left ventricular remodeling in a hamster model of dilated cardiomyopathy by enhanced homing of bone marrow mesenchymal stem cells into damaged myocardium, suggesting that high-mobility group box 1 fragment could be a new treatment for dilated cardiomyopathy.
Role of the high-affinity leukotriene B4receptor signaling in fibrosis after unilateral ureteral obstruction in mice
Authors: Kamata Mariko , Amano Hideki , Ito Yoshiya , Fujita Tomoe , Hosono Kanako , Kamata Kouju , Takeuchi Yasuo , Yokomizo Takehiko , Shimizu Takao , Majima Masataka
Published: August 2018

Leukotriene B4(LTB4) is a lipid mediator that acts as a potent chemoattractant for inflammatory leukocytes. Kidney fibrosis is caused by migrating inflammatory cells and kidney-resident cells. Here, we examined the role of the high-affinity LTB4receptor BLT1 during development of kidney fibrosis in wild-type (WT) mice and BLT1 knockout (BLT1-/-) mice with unilateral ureteral obstruction (UUO). We found elevated expression of 5-lipoxygenase (5-LOX), which generates LTB4, in the renal tubules of WT and BLT1-/-UUO mice. Accumulation of immunoreactive type I collagen in UUO kidneys of WT mice increased over time; however, the increase was less prominent in BLT1-/-mice. Accumulation of S100A4-positive fibroblasts also increased temporally in WT UUO kidneys, but was again less pronounced in those of BLT1-/-mice. The same was true of mRNA encoding transforming growth factor-β (TGF)-β and fibroblast growth factor (FGF)-2. Finally, accumulation of F4/80-positive macrophages, which secrete TGF-β, also increased temporally in WT UUO and BLT1-/-kidneys, but to a lesser extent in the latter. Following LTB4stimulationin vitro, macrophages showed increased expression of mRNA encoding TGF-β/FGF-2 and Col1a1, whereas L929 fibroblasts showed increased expression of mRNA encoding α smooth muscle actin (SMA). Bone marrow (BM) transplantation studies revealed that the area positive for type I collagen was significantly smaller in BLT1-/--BM→WT UUO kidneys than in WT-BM→WT kidneys. Thus, LTB4-BLT1 signaling plays a critical role in fibrosis in UUO kidneys by increasing accumulation of macrophages and fibroblasts. Therefore, blocking BLT1 may prevent renal fibrosis.
Cracking the problem of neural representations of abstract words: grounding word meanings in language itself
Authors: Hultén Annika , van Vliet Marijn , Lammi Lotta , Kivisaari Sasa , Lindh-Knuutila Tiina , Faisal Ali , Salmelin Riitta
Published: August 2018

In order to describe how humans represent meaning in the brain, one must be able to account for not just concrete words but, critically, also abstract words which lack a physical referent. Hebbian formalism and optimization are basic principles of brain function, and they provide an appealing approach for modeling word meanings based on word co-occurrences. Here, we built a model of the semantic space based on word statistics in a large text corpus, which was able to decode items from brain signals. In the model, word abstractness emerged from the statistical regularities of the language environment. This salient property of the model co-varied, at 280–420 ms after word presentation, with activity in the left-hemisphere frontal, anterior temporal and superior parietal cortex that have been linked with processing of abstract words. In light of these results, we propose that the neural encoding of word meanings is importantly grounded in language through statistical regularities.
Sucrose intensity coding and decision-making in rat gustatory cortices
Authors: Fonseca Esmeralda , Lafuente Victor de , Simon Sidney A. , Gutierrez Ranier
Published: August 2018

Sucrose’s sweet intensity is one attribute contributing to the overconsumption of high-energy palatable foods. However, it is not known how sucrose intensity is encoded and used to make perceptual decisions by neurons in taste-sensitive cortices. We trained rats in a sucrose intensity discrimination task and found that sucrose evoked a widespread response in neurons recorded in posterior-Insula (pIC), anterior-Insula (aIC), and Orbitofrontal cortex (OFC). Remarkably, only a few Intensity-selective neurons conveyed the most information about sucrose’s intensity, indicating that for sweetness the gustatory system used a compact and distributed code. Sucrose intensity was encoded in both firing-rates and spike-timing. The pIC, aIC, and OFC neurons tracked movement direction, with OFC neurons yielding the most robust response. aIC and OFC neurons encoded the subject’s choices, whereas all three regions tracked reward omission. Overall, these multimodal areas provide a neural representation of perceived sucrose intensity, and of task-related information underlying perceptual decision-making.
Emerging financial risks from climate changes on building assets in the UK
Authors: Alzahrani Abdullah , Boussabaine Halim , Almarri Khalid
Published: August 2018

Purpose

The different scenarios of climate change, such as floods, temperature change and storms, are considered the main drivers influencing the building sector. Understanding how and when these climatic risks will emerge, specifically financial risks, is pivotal in dealing with these risks and applying the adaptation and mitigation strategies so as to minimise the effects and damages. Thus, the purpose of this paper is to discover the financial risks emerging from climate change impact on the building sector and determine the timescale of occurrence for such risks.

Design/methodology/approach

The research methodology formulated in this study is founded on a systematic literature review and statistical analysis. Built on this, the potential financial risks emerging from climate change scenarios (CCS) were identified and designed as a questionnaire to collect data from UK expert professionals. Statistical methods were used to rank and compare the outcomes of the survey.

Findings

The research observed that around 40 per cent of the participants in this study indicated that one-third of the total identified financial risks (23 factors) would emerge within 5-10 years. The most important factors are increased insurance excess and additional expense in insuring buildings in flood risk zones, whilst the least important financial risks are inability to repay debts and un-insurability because of climate change.

Research limitations/implications

This study is limited to the UK, and regional implications are not covered. However, it is a starting point.

Originality/value

The main contribution of this research project is establishing and developing clusters of the potential risks emerging from CCS, which can assist professionals in the building sector in the management and development of strategies to cope with these emerging risks.
Is job satisfaction of high-level managers and self-employed more pro-cyclical than normal employees?
Authors: Sánchez-Sánchez Nuria , Namkee Ahn
Published: August 2018

Purpose

The recent economic crisis in Spain is felt most severely in the labour market. The purpose of this paper is to examine job satisfaction among the occupied workers according to their job types throughout the ongoing economic cycle comparing the period of boom and that of bust.

Design/methodology/approach

Surprisingly, the average job satisfaction has stayed virtually constant between the two periods, which suggests the existence of compensating forces operating among the occupied population. The authors find first the compositional change of working population, such as a decreasing proportion of temporary contract workers had only small effects, unable to explain the puzzle. The authors also find that macroeconomic conditions affect workers’ job satisfaction differently by the type of workers or jobs. In fact, high-level managerial workers and self-employed employers have suffered a significantly large reduction in their job satisfaction during the crisis while some other types of workers such as ordinary employees have enjoyed increased job satisfaction. In order to explore the causes of these differences, the authors examine the satisfaction in different job domains.

Findings

The results suggest that in the case of self-employed, decrease in job satisfaction with respect to wages job stability superior evaluation is significant and the promotion prospect is not relevant for self-employed, while for managerial workers, the only significant decrease is due to superior evaluation.

Research limitations/implications

The Spanish data with a reasonable sample size which include information on job satisfaction are the Spanish Survey of Life Quality at Work. Unfortunately, the survey is not longitudinal, therefore unable to examine the factors affecting transitions in satisfaction level or to control for fixed individual effects, and the data only cover until 2010. Further investigation including more recent data and data from other countries would be helpful to better understand the consequences of economic crisis on job satisfaction.

Originality/value

This paper contributes in two ways. First, the authors show what has been happening to the job-related well-being during the recession in Spain by the type of workers: high-level managers, managers, self-employed and employees. Job satisfaction can be determined by pressures to work harder and longer hours, reduced wages, lower promotion possibility and higher layoff probability, and all of them could have been changed by the economic crisis. Consequently, the second contribution is to analyse different dimensions of job satisfaction as satisfaction with wages, flexibility, stability, stress and promotion to determine the causes of the changes in average level of job satisfaction.
Public provision of employment support services to youth jobseekers
Authors: Petreski Marjan
Published: August 2018

Purpose

The purpose of this paper is to investigate if public provision of employment support services to youth leads to reduced informality and increased wages in transition economies.

Design/methodology/approach

The author uses the school-to-work transition data sets of the International Labor Organization for seven transition economies of Southeast Europe and the Commonwealth of Independent States. The author focuses on two econometric issues: the selectivity into informal employment and the endogeneity of the public employment support service provision with respect to informal employment and wages. The authors achieves identification by employing internal regressors which are uncorrelated with the product of heteroskedastic errors, a-la Lewbel (2012), as the author could not prove the external validity of the commonly used external instruments in similar contexts.

Findings

Results suggest that the public provision of employment support services matters for relegating informal employment, but not for wages, in general. Placement in education or training programs is most powerful in reducing informal employment among the four different employment support services, while only advice for job search works positively for wages probably through enabling better match.

Social implications

Increasing budget allocations, varying the array of public employment support measures, enhanced targeting, and advancement of the profiling system may significantly contribute to strengthening the public employment support service effect on youth employment in transition economies.

Originality/value

The paper brings a couple of novelties to the current literature. First, it is among the early papers dealing with the issue of informality, public employment support service and labor market prospects of youth in general in a rigorous manner. Second, it fills an important gap for transition economies which were less researched due to the long-lasting transition process as well due to data scarcity. Third, it utilizes the recently collected School-to-Work Transition Surveys (SWTS). Finally, and likely most importantly, it thoroughly addresses the issues of selectivity bias and endogeneity of PESS by utilizing a recent approach of Lewbel (2012) whereby internally generated variables are used as instruments. Hence, the paper accounts for the endogeneity stemming from unobservables in a novel manner, contrary to the common approaches in the literature based either on propensity score matching addressing selectivity on observables only, or relying on commonly used instruments in the labor market literature – mainly regional employment variables – whose external validity is easily disputed.
Financial inclusion matters for economic growth in India
Authors: Sethi Dinabandhu , Sethy Susanta Kumar
Published: August 2018

Purpose

The purpose of this paper is to examine the relationship between financial inclusion (FI) and economic growth in India.

Design/methodology/approach

To measure FI, a multidimensional time-varying index is proposed following the Human Development Index method. The long-run relationship between FI and economic growth is examined by using the autoregressive distributed lag (ARDL) approach to cointegration and nonlinear ARDL approach. Further, the direction of causality is investigated by employing the Toda–Yamamoto Granger causality test.

Findings

The linear cointegration test confirms a long-run relationship between FI and economic growth for India. The improvement in both demand-side and supply-side financial services has a positive impact on economic growth. These results suggest that India can attain long-run economic growth by improving the coverage of FI. However, there is no evidence of nonlinear cointegration, indicating that there is no asymmetric effect of FI on economic growth. Further, the causality test shows that FI granger causes economic growth but not vice versa.

Research limitations/implications

The major limitation of the study is the availability of time series data for all important variables. The index for both demand- and supply-side indicators can be extended with several other important variables in later date once the data are available for those variables.

Practical implications

As the study confirms that FI is one of the main drivers of economic growth, it is suggested that the policy maker emphasizing on financial sector reforms can enjoy economic growth in the long run, especially in developing countries. Therefore, the government and policy makers need to address the issues involved in access to financial services to spur economic growth.

Originality/value

The study examines the long-run relationship between FI and economic growth employing ARDL bound testing approach and nonlinear ARDL approach, separately for demand-side and supply-side indicators. Further, the study uses the Toda–Yamamoto granger causality to find the direction of causal flow between FI and economic growth.
The role of the consistency between objective and perceived environmental uncertainty in supply chain risk management
Authors: Yu Kangkang , Cadeaux Jack , Luo Nanfeng , Qian Cheng , Chen Zhenghao
Published: August 2018

Purpose

The purpose of this paper is to understand how the consistency between objective and perceived environmental uncertainty might affect supply chain flexibilities that cope with supply chain risk.

Design/methodology/approach

This study adopted a case study of comparative four companies in order to obtain an in-depth knowledge of the environmental conditions under which the companies implement different types of supply chain risk management (SCRM) strategies: logistics flexibility and relationship flexibility.

Findings

The case analysis not only distinguished the different effects of objective and perceived environmental uncertainty on supply chain flexibility, but also established the propositions about the effects of the consistency between objective and perceived environmental uncertainty on logistics flexibility and relationship flexibility in SCRM.

Originality/value

In principle, supply chain flexibility aims to cope with complex and turbulent environments. Yet, empirical findings about the effects of environmental uncertainty on supply chain flexibility are inconclusive. This study addressed this question by differentiating between objective and perceived environmental uncertainty as well as between logistics and relationship supply chain flexibilities.
Refugee special economic zones
Authors: Moberg Lotta , Reil Sebastian
Published: August 2018

Purpose

The purpose of this paper is to show how special economic zones (SEZs) can be applied to refugee camps. Zones are powerful tools for investors to act like institutional entrepreneurs, who promote institutional reform by pursuing exemptions from government constraints and taxes or by advocating for reform. Refugee SEZs (R-SEZs) would similarly allow for institutional entrepreneurs to promote broader immigration reform.

Design/methodology/approach

The authors apply a political economy framework to R-SEZs that explores the factors that make them feasible. A mathematical model is applied to explicitly define the conditions under which the zones could succeed in benefiting refugees, investors and the host economy alike.

Findings

Under certain conditions, appropriate tax rates can be applied to R-SEZs that make them feasible. Feasibility is determined by being beneficial for the host country while also attracting investors. The zones are feasible if they attract enough foreign investors as opposed to domestic investors. Other factors contributing to zone success are higher wages outside the zone, lower wages inside it, higher cost to the government of non-employed refugees, lower relocation cost for businesses and a higher tax rate outside the zone.

Practical implications

This policy would aim to provide job opportunities to refugees, profit opportunities to investors and lower net costs for the host government. R-SEZs should be considered by policy makers in countries hosting refugee camps. Just like the old model of SEZs, they can benefit workers while also enhancing the government’s budget.

Social implications

R-SEZs have the potential to alleviate the refugee crisis the world is facing, which is arguably one of the largest social challenges of our time.

Originality/value

This paper is the first to outline the political economy conditions for SEZs applied to refugee camps.
Involuntary delisting in the Japanese stock market
Authors: Park Jinwoo , Shiroshita Kengo , Sun Naili , Park Yun W.
Published: August 2018

Purpose

The purpose of this paper is to analyze the wealth effect of involuntary delisting and investigate insider opportunism and the role of corporate governance, liquidity and legal environment in involuntary delisting in Japan’s stock market.

Design/methodology/approach

The authors use a sample of 136 involuntarily delisted firms in Japan’s stock markets between 2002 and 2012. The authors examine ownership changes of inside shareholders prior to delisting and estimate regression models for the wealth effect of involuntary delisting.

Findings

Involuntary delisting is highly disruptive in Japan, and limited liquidity of delisted stocks appears to be an important cause. However, the ownership reduction of inside shareholders before delisting is limited, totaling 2–3 percent. For delisted firms with an insider bank, the decrease in share price leading up to a delisting announcement is much less, while the decrease in share price upon a delisting announcement is far greater.

Originality/value

The study investigates involuntary delisting in regard to the opportunistic behavior of inside shareholders and the role of institutional environment in Japan’s stock market. Insiders, especially insider banks, maintain ownership in a distressful context leading to the forcible delisting of a distressed firm. The authors find some evidence that suggests that the market believes the insider bank will try to prevent the ailing firm’s insolvency. The findings are consistent with the implicit relational contracts that characterize Japanese firms.