bluuebunny/crossref_metadata_2025 huggingface dataset:
Fever in returning travellers and migrants: disease severity markers to improve triage and management
Authors: Ngai Michelle , Kain Kevin C
Published: May 2019

Pathogen-based rapid diagnostic tests (RDTs) can identify the presence or absence of infection, but do not indicate who will have a self-limited infection versus a life-threatening one. An RDT that incorporates disease severity markers could facilitate the triage and management of travellers and migrants presenting with fever.
Multiple Independent Recruitment of Sodefrin Precursor-Like Factors in Anuran Sexually Dimorphic Glands
Authors: Bossuyt Franky , Schulte Lisa M , Maex Margo , Janssenswillen Sunita , Novikova Polina Yu , Biju S D , Van de Peer Yves , Matthijs Severine , Roelants Kim , Martel An , Van Bocxlaer Ines
Published: May 2019

Chemical signaling in animals often plays a central role in eliciting a variety of responses during reproductive interactions between males and females. One of the best-known vertebrate courtship pheromone systems is sodefrin precursor-like factors (SPFs), a family of two-domain three-finger proteins with a female-receptivity enhancing function, currently only known from salamanders. The oldest divergence between active components in a single salamander species dates back to the Late Paleozoic, indicating that these proteins potentially gained a pheromone function earlier in amphibian evolution. Here, we combined whole transcriptome sequencing, proteomics, histology, and molecular phylogenetics in a comparative approach to investigate SPF occurrence in male breeding glands across the evolutionary tree of anurans (frogs and toads). Our study shows that multiple families of both terrestrially and aquatically reproducing frogs have substantially increased expression levels of SPFs in male breeding glands. This suggests that multiple anuran lineages make use of SPFs to complement acoustic and visual sexual signaling during courtship. Comparative analyses show that anurans independently recruited these proteins each time the gland location on the male’s body allowed efficient transmission of the secretion to the female’s nares.
Vulpes chama (Carnivora: Canidae)
Authors: Lavoie Maxime , Renard Aurélie , Pitt Justin A , Larivière Serge
Published: May 2019

Vulpes chama (Smith, 1833), commonly called the Cape fox, is 1 of 11 species of Vulpes. It is the only species of Vulpes occurring in southern Africa, and is endemic to that region. It occurs in southern Angola, Botswana, Namibia, South Africa, and southwestern Zimbabwe. V. chama is a slender-built fox and its pelage is silvery gray throughout, back of pinna is tawny, and white hairs occur in the front along pinna edge. It tends to occupy arid and semiarid open habitats and feeds mainly on small mammals and insects, but also consumes birds, small reptiles, and fruits. V. chama is not of conservation concern and is listed as “Least Concern” by the International Union for the Conservation of Nature and Natural Resources.
Change in mutation frequency at a TP53 hotspot during culture of ENU-mutagenised human lymphoblastoid cells
Authors: Watanabe Masahiko , Toudou Masae , Uchida Taeko , Yoshikawa Misato , Aso Hiroaki , Suemaru Katsuya
Published: May 2019

Mutations in oncogenes or tumour suppressor genes cause increases in cell growth capacity. In some cases, fully malignant cancer cells develop after additional mutations occur in initially mutated cells. In such instances, the risk of cancer would increase in response to growth of these initially mutated cells. To ascertain whether such a situation might occur in cultured cells, three independent cultures of human lymphoblastoid GM00130 cells were treated with N-ethyl-N-nitrosourea to induce mutations, and the cells were maintained for 12 weeks. Mutant frequencies and spectra of the cells at the MspI and HaeIII restriction sites located at codons 247–250 of the TP53 gene were examined. Mutant frequencies at both sites in the gene exhibited a declining trend during cell culture and reached background levels after 12 weeks; this was also supported by mutation spectra findings. These results indicate that the mutations detected under our assay conditions are disadvantageous to cell growth.
A large-scale drug screen identifies selective inhibitors of class I HDACs as a potential therapeutic option for SHH medulloblastoma
Authors: Pak Ekaterina , MacKenzie Ethan L , Zhao Xuesong , Pazyra-Murphy Maria F , Park Paul M C , Wu Lei , Shaw Daniel L , Addleson Emily C , Cayer Suzanne S , Lopez Begoña G-C , Agar Nathalie Y R , Rubin Lee L , Qi Jun , Merk Daniel J , Segal Rosalind A
Published: May 2019

Background

Medulloblastoma (MB) is one of the most frequent malignant brain tumors of children, and a large set of these tumors is characterized by aberrant activation of the sonic hedgehog (SHH) pathway. While some tumors initially respond to inhibition of the SHH pathway component Smoothened (SMO), tumors ultimately recur due to downstream resistance mechanisms, indicating a need for novel therapeutic options.

Methods

Here we performed a targeted small-molecule screen on a stable, SHH-dependent murine MB cell line (SMB21). Comprehensive isotype profiling of histone deacetylase (HDAC) inhibitors was performed, and effects of HDAC inhibition were evaluated in cell lines both sensitive and resistant to SMO inhibition. Lastly, distinct mouse models of SHH MB were used to demonstrate pharmacologic efficacy in vivo.

Results

A subset of the HDAC inhibitors tested significantly inhibit tumor growth of SMB21 cells by preventing SHH pathway activation. Isotype profiling of HDAC inhibitors, together with genetic approaches suggested that concerted inhibition of multiple class I HDACs is necessary to achieve pathway inhibition. Of note, class I HDAC inhibitors were also efficacious in suppressing growth of diverse SMO inhibitor‒resistant clones of SMB21 cells. Finally, we show that the novel HDAC inhibitor quisinostat targets multiple class I HDACs, is well tolerated in mouse models, and robustly inhibits growth of SHH MB cells in vivo as well as in vitro.

Conclusions

Our data provide strong evidence that quisinostat or other class I HDAC inhibitors might be therapeutically useful for patients with SHH MB, including those resistant to SMO inhibition.
Atraumatic Sylvian Fissure Split: Nuances and Pitfalls
Authors: Cohen-Gadol Aaron A
Published: May 2019

An appropriately wide, efficient, and atraumatic split of the Sylvian fissure is technically challenging; this task does not often receive the respect or attention it deserves. Mastering efficient fissure dissection is imperative for protecting the cerebrovascular structures and using dynamic retraction for optimal exposure of the lesions within the peri-insular region and around the circle of Willis.
Construction of an ICF core set and ICF-based questionnaire assessing activities and participation in patients with systemic sclerosis
Authors: Papelard Agathe , Daste Camille , Alami Sophie , Sanchez Katherine , Roren Alexandra , Segretin François , Lefèvre-Colau Marie-Martine , Rannou François , Mouthon Luc , Poiraudeau Serge , Nguyen Christelle
Published: May 2019

Objectives

To develop an International Classification of Functioning, Disability and Health (ICF) core set for SSc and to conceive a patient-centred ICF-based questionnaire assessing activities and participation in patients with SSc.

Methods

The construction of the ICF core set followed two steps. In the first step, meaningful concepts related to SSc were collected using data source triangulation from patients (n = 18), experts (n = 10) and literature (n = 174 articles). In the second step, concepts were linked to the best-matching ICF categories by one reviewer according to prespecified linking rules. Finally, patient-reported activities and participation categories of the ICF core set were translated into understandable questions.

Results

After linking concepts to ICF categories, 150 ICF categories were collected from focus groups, 22 from experts and 82 from literature. After fusion of the sources and removal of duplicates, the ICF core set included 164 categories: one at the first level, 157 at the second level and six at the third level, with 50 categories on body functions, 15 on body structures, 52 on activities and participation, and 47 on environmental factors. Patient-reported ICF categories on activities and participation were translated into a patient-centred ICF-based 65-item questionnaire.

Conclusion

The present study proposes an ICF core set that offers a conceptual framework for SSc patients’ care and health policy. Using a patient-centred approach, a patient-centred ICF-based questionnaire, the Cochin Scleroderma ICF-65 questionnaire, assessing activities and participation in patients with SSc, was conceived.

Trial registration

ClinicalTrials.gov, http://clinicaltrials.gov, NCT01848418.
Prenatal Practice Staff Perceptions of Three Substance Use Screening Tools for Pregnant Women
Authors: Trocin Kathleen E. , Weinstein Nicole I. , Oga Emmanuel A. , Mark Katrina S. , Coleman-Cowger Victoria H.
Published: May 2019

Objective:

There is a need to identify an acceptable and comprehensive substance use screening tool for pregnant women in the United States. This qualitative study sought to better understand prenatal practice staff perceptions of three existing substance use screening tools for use among pregnant women in an outpatient practice setting.

Methods:

Eight focus groups with 40 total participants were conducted with clinical and administrative staff of 2 diverse Maryland prenatal practices to determine the acceptability and usability of 3 substance use screening tools (4P's Plus, NIDA-Modified Alcohol, Smoking and Substance Involvement Screening Test, and the Substance Use Risk Profile-Pregnancy scale). The focus groups were digitally recorded, transcribed, coded, and analyzed using thematic analysis.

Results:

Participant perceptions of screening tools were dependent upon screening tool length, tone, comprehensiveness, subjectivity, time frame of questions, and scoring and clinician instructions. Most participants preferred the 4P's Plus screening tool because it is brief, comprehensive, easy for the patient to understand, and excludes judgmental language and subjective questions.

Conclusions:

These results provide valuable insight into the specific needs and preferences of prenatal practice staff as it relates to prenatal substance use screening and provides evidence that the 4P's Plus may be a preferred screening tool for standardized use in prenatal care.
Functionally Defective T Cells After Chemotherapy of B-Cell Malignancies Can Be Activated by the Tetravalent Bispecific CD19/CD3 Antibody AFM11
Authors: Duell Johannes , Lukic Dragana S. , Karg Margarete , Reusch Uwe , Koch Joachim , Zhukovsky Eugene A. , Rajkovic Erich , Treder Martin , Rasche Leo , Eisele Florian , Einsele Hermann , Topp Max S.
Published: May 2019

Immunotherapy of B-cell malignancies with bispecific antibodies is an emerging treatment option. However, not all patients benefit from these therapies, presumably due to pretreatment regimens. Therefore, we determined the effect of different treatment lines on the activity of T cells and their responsiveness to AFM11. AFM11 is a tetravalent, bispecific CD19/CD3 immunoengager based on Affimed’s ROCK platform, currently being investigated in phase I clinical trials for non-Hodgkin lymphoma and acute lymphoblastic leukemia. T cells from B-cell lymphoma patients treated with either rituximab+bendamustine (R-Benda), rituximab+CHOP (R-CHOP), or with high-dose BEAM chemotherapy (HD-BEAM) and autologous HSCT were compared with T cells from healthy donors. Overall, in these patients, T-cell numbers were significantly reduced. To determine whether distinct chemotherapy affects AFM11 efficacy, functional T-cell assays were performed. It is interesting to note that, only in assays that combine target cell lysis, cytokine production and proliferation over 4 days at an effector to target ratio of up to 1:25 significant differences could be detected between the different treatment groups: T cells after R-CHOP showed only modest decrease in their functionality when compared with healthy controls, whereas R-Benda and HD-BEAM had a profound effect on AFM11-induced T-cell cytotoxicity. In conclusion, T cells from lymphoma patients are reduced in number and have functional defects following treatment with certain chemotherapy regimens, also reducing AFM11 efficacy. Importantly, AFM11 was still able to trigger B-cell-directed T-cell immunity in all treatment groups.
ONE-YEAR OUTCOMES OF A NOVEL SURGICAL TECHNIQUE FOR SUTURELESS INTRASCLERAL FIXATION OF A THREE-PIECE INTRAOCULAR LENS USING A 30-GAUGE NEEDLE
Authors: Bonnell Alyssa C. , Polo Richard N. , Shah Sumit P. , Fine Howard F. , Prenner Jonathan L.
Published: May 2019

Purpose:

To present the 1-year results of a surgical technique for the sutureless intrascleral fixation of a 3-piece intraocular lens using a 30-gauge needle.

Methods:

A retrospective chart review of a consecutive series of 9 eyes of 8 patients who underwent sutureless intrascleral fixation of posterior chamber intraocular lens using a 30-gauge needle was performed. Patients were required to have at least 1 year of follow-up to be included in the analysis. Short-term data were collected 1 month after surgery, and long-term data were collected 1 year after surgery. Data collected included visual acuity, lens stability, intraocular pressure, and the development of complications.

Results:

Visual acuity improved from Snellen 20/309 preoperatively to Snellen 20/27 at postoperative Month 12 (P = 0.03). Short-term complications included increased intraocular pressure (n = 4) and corneal edema (n = 2). Long-term complications included exposed superior haptic (n = 1) and recurrent anterior chamber inflammation (n = 1).

Conclusion:

The novel surgical technique for sutureless intrascleral fixation of a 3-piece intraocular lens is well tolerated 1 year after surgery.
CENTRAL RETINAL VEIN OCCLUSION IN OTHERWISE HEALTHY CHILDREN AND ADOLESCENTS
Authors: Bremond-Gignac Dominique , Daruich Alejandra , Gallet Marlène , Menoud Pierre Alain , Nowomiejska Katarzyna , Rejdak Robert , Behar-Cohen Francine , Benkhalifa Moncef , Copin Henri
Published: May 2019

Purpose:

To report cases of central retinal vein occlusion in otherwise healthy children showing combined genetic variants of thrombophilia.

Methods:

Ophthalmological, pediatric records and genetic analyses of thrombophilia-associated variants were retrospectively reviewed in four children diagnosed with central retinal vein occlusion. Genetic screening, including Factor XII, platelet glycoprotein (GP) IIIa PlA1/A2 (rs5918), and GPIa/IIa C807T (rs1126643) and G873A (rs1062535) mutations, was performed by PCR amplification and Sanger sequencing of PCR products. The genotyping of prothrombin G20210A, Leiden Factor V G1691A, methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C mutations, and plasminogen activator inhibitor-1 4G/5G polymorphisms was performed by real-time PCR with Fluorescence Resonance Energy Transfer (FRET) probes.

Results:

The genotyping analysis identified combined genetic variants of thrombophilia in each patient. Mutations for MTHFR (C677T) and GPIIIa PlA1/A2 were detected in Case 1, mutations for MTHFR (C677T), GPIIIa PlA1/A2, and GPIa/IIa in Case 2, mutations for MTHFR (C677T) and GPIa/IIa in Case 3, and mutation for MTHFR (A12986C), GPIIIa Pl A1/A2, and GPIa/IIa in Case 4. Preventive low-dose aspirin therapy was prescribed to all patients. During a follow-up of 5 and 8 years, neither central retinal vein occlusion recurrence nor any other thrombotic event was observed in Cases 1 and 2, respectively.

Conclusion:

In otherwise healthy children presenting central retinal vein occlusion, genetic investigations for thrombophilia-associated variants should be considered, given the possible long-term benefit of aspirin prophylaxis.
Surgery for adhesive small-bowel obstruction is associated with improved long-term survival mediated through recurrence prevention: A population-based, propensity-matched analysis
Authors: Behman Ramy , Nathens Avery B. , Haas Barbara , Look Hong Nicole , Pechlivanoglou Petros , Karanicolas Paul
Published: May 2019

BACKGROUND

Adhesive small-bowel obstruction (aSBO) is among the most common reasons for admission to a surgical service. While operative intervention for aSBO is associated with a lower risk of recurrence, current guidelines continue to advocate a trial of nonoperative management. The impact of the increased risk for recurrence on long-term survival is unknown. We sought to explore the potential for improved survival with operative management through the prevention of admissions for recurrence of aSBO and the associated risks.

METHODS

This is a population-based retrospective cohort study using administrative data. We identified patients admitted to hospital for their first episode of aSBO from 2005 to 2014 and created a propensity-matched cohort to compare survival of patients managed operatively with those managed nonoperatively. To test whether survival differences were mediated by recurrence prevention, a competing risk regression was used to model the subdistribution hazard of death when accounting for the risk of recurrence. An instrumental variable approach was used as a secondary analysis to compare survival while accounting for unmeasured confounding.

RESULTS

There were 27,904 patients admitted for their first episode of aSBO between 2005 and 2014. The mean age was 61.2 years (std dev, 13.6), and 51% were female. Operative management was associated with a significantly lower risk of death (hazard ratio, 0.80; 95% confidence interval, 0.75–0.86), which was robust to instrumental variable analyses, and a lower risk of recurrence (hazard ratio, 0.59; 95% confidence interval, 0.54–0.65). When adjusting for the risk of recurrence, operative intervention was not associated with improved survival, suggesting that the survival benefit is mediated through prevention of recurrences of aSBO.

CONCLUSION

In patients admitted for their first episode of aSBO, operative intervention is associated with a significant long-term survival benefit. This survival benefit appears to be mediated through the prevention of recurrences of aSBO.

STUDY TYPE

Retrospective cohort study.

LEVEL OF EVIDENCE

Therapeutic study, Level II.
Adaptive post-transcriptional reprogramming of metabolism limits response to targeted therapy in BRAFV600 melanoma
Authors: Smith Lorey K , Parmenter Tiffany , Kleinschmidt Margarete , Kusnadi Eric P , Kang Jian , Martin Claire A , Lau Peter , Lorent Julie , Trigos Anna , Ward Teresa , Rao Aparna D , Lelliott Emily J , Sheppard Karen E , Goode David , Hicks Rodney J , Tiganis Tony , Simpson Kaylene J , Larsson Ola , Cullinane Carleen , Wickramasinghe Vihandha O , Pearson Richard B , McArthur Grant A
Published: May 2019

Despite the success of therapies targeting oncogenes in cancer, clinical outcomes are limited by a residual disease that results in relapse. This residual disease is characterized by drug-induced adaptation, that in melanoma includes altered metabolism. Here, we examined how targeted therapy reprograms metabolism in BRAF-mutant melanoma cells using a genome-wide RNAi screen and global gene expression profiling. This systematic approach revealed post-transcriptional regulation of metabolism following BRAF inhibition, involving selective mRNA transport and translation. As proof of concept we demonstrate the RNA binding kinase UHMK1 interacts with mRNAs that encode metabolic proteins and selectively controls their transport and translation during adaptation to BRAF targeted therapy. Inactivation of UHMK1 improves metabolic response to BRAF targeted therapy and delays resistance to BRAF and MEK combination therapy in vivo. Our data support a model wherein post-transcriptional gene expression pathways regulate metabolic adaptation underpinning targeted therapy response and suggest inactivation of these pathways may delay disease relapse.
Scalable dynamic characterization of synthetic gene circuits
Authors: Dalchau Neil , Grant Paul K. , Vaidyanathan Prashant , Spaccasassi Carlo , Gravill Colin , Phillips Andrew
Published: May 2019

The dynamic behavior of synthetic gene circuits plays a key role in ensuring their correct function. Although there has been substantial work on modeling dynamic behavior after circuit construction, the forward engineering of dynamic behavior remains a major challenge. Previous engineering methods have focused on quantifying average behaviors of circuits over an extended time window, however this provides a static characterization of behavior that is a poor predictor of dynamics. Here we present a method for characterizing the dynamic behavior of synthetic gene circuits, using parameter inference of dynamical system models applied to time-series measurements of cell cultures growing in microtiter plates. We demonstrate that the behaviors of simple devices can be characterized dynamically and used to predict the behaviors of more complex circuits. Specifically, we compose 23 biological parts into 9 devices and use them to design 9 synthetic gene circuits in E. coli that provide core functionality for engineering cell behavior at the population level, including relays, receivers and a degrader. We embody our method in a software package and corresponding programming language. Our method supports the notion of an inference graph for iterative inference of models as new circuits are constructed, without the need to infer all models from scratch, and lays the foundation for characterizing large libraries of synthetic gene circuits in a scalable manner.
Genome-wide association study of susceptibility to idiopathic pulmonary fibrosis
Authors: Allen Richard J , Guillen-Guio Beatriz , Oldham Justin M , Ma Shwu-Fan , Dressen Amy , Paynton Megan L , Kraven Luke M , Obeidat Ma’en , Li Xuan , Ng Michael , Braybrooke Rebecca , Molina-Molina Maria , Hobbs Brian D , Putman Rachel K , Sakornsakolpat Phuwanat , Booth Helen L , Fahy William A , Hart Simon P , Hill Mike R , Hirani Nik , Hubbard Richard B , McAnulty Robin J , Millar Ann B , Navaratnam Vidyia , Oballa Eunice , Parfrey Helen , Saini Gauri , Whyte Moira K B , Gudmundsson Gunnar , Gudnason Vilmundur , Hatabu Hiroto , Lederer David J , Manichaikul Ani , Newell John D , O’Connor George T , Ortega Victor E , Xu Hanfei , Fingerlin Tasha E , Bossé Yohan , Hao Ke , Joubert Philippe , Nickle David C , Sin Don D , Timens Wim , Furniss Dominic , Morris Andrew P , Zondervan Krina , Hall Ian P , Sayers Ian , Tobin Martin D , Maher Toby M , Cho Michael H , Hunninghake Gary M , Schwartz David A , Yaspan Brian L , Molyneaux Philip L , Flores Carlos , Noth Imre , Jenkins R Gisli , Wain Louise V
Published: May 2019

Rationale

Idiopathic pulmonary fibrosis (IPF) is a complex lung disease characterised by scarring of the lung that is believed to result from an atypical response to injury of the epithelium. The mechanisms by which this arises are poorly understood and it is likely that multiple pathways are involved. The strongest genetic association with IPF is a variant in the promoter of MUC5B where each copy of the risk allele confers a five-fold risk of disease. However, genome-wide association studies have reported additional signals of association implicating multiple pathways including host defence, telomere maintenance, signalling and cell-cell adhesion.

Objectives

To improve our understanding of mechanisms that increase IPF susceptibility by identifying previously unreported genetic associations.

Methods and measurements

We performed the largest genome-wide association study undertaken for IPF susceptibility with a discovery stage comprising up to 2,668 IPF cases and 8,591 controls with replication in an additional 1,467 IPF cases and 11,874 controls. Polygenic risk scores were used to assess the collective effect of variants not reported as associated with IPF.

Main results

We identified and replicated three new genome-wide significant (P<5×10-8) signals of association with IPF susceptibility (near KIF15, MAD1L1 and DEPTOR) and confirm associations at 11 previously reported loci. Polygenic risk score analyses showed that the combined effect of many thousands of as-yet unreported IPF risk variants contribute to IPF susceptibility.

Conclusions

Novel association signals support the importance of mTOR signalling in lung fibrosis and suggest a possible role of mitotic spindle-assembly genes in IPF susceptibility.
The representation of two-body shapes in the human visual cortex
Authors: Etienne Abassi , Liuba Papeo
Published: May 2019

Human social nature has shaped visual perception. A signature of the relationship between vision and sociality is a particular visual sensitivity to social entities such as faces and bodies. We asked whether human vision also exhibits a special sensitivity to spatial relations that reliably correlate with social relations. In general, interacting people are more often situated face-to-face than back-to-back. Using functional MRI and behavioral measures in female and male human participants, we show that visual sensitivity to social stimuli extends to images including two bodies facing toward (vs. away from) each other. In particular, the inferior lateral occipital cortex, which is involved in visual-object perception, is organized such that the inferior portion encodes the number of bodies (one vs. two) and the superior portion is selectively sensitive to the spatial relation between bodies (facing vs. non-facing). Moreover, functionally localized, body-selective visual cortex responded to facing bodies more strongly than identical, but non-facing, bodies. In this area, multivariate pattern analysis revealed an accurate representation of body dyads with sharpening of the representation of single-body postures in facing dyads, which demonstrates an effect of visual context on the perceptual analysis of a body. Finally, the cost of body inversion (upside-down rotation) on body recognition, a behavioral signature of a specialized mechanism for body perception, was larger for facing vs. non-facing dyads. Thus, spatial relations between multiple bodies are encoded in regions for body perception and affect the way in which bodies are processed.

Public Significance Statement

Human social nature has shaped visual perception. Here, we show that human vision is not only attuned to socially relevant entities, such as bodies, but also to socially relevant spatial relations between those entities. Body-selective regions of visual cortex respond more strongly to multiple bodies that appear to be interacting (i.e., face-to-face), relative to unrelated bodies, and more accurately represent single body postures in interacting scenarios. Moreover, recognition of facing bodies is particularly susceptible to perturbation by upside-down rotation, indicative of a particular visual sensitivity to the canonical appearance of facing bodies. This encoding of relations between multiple bodies in areas for body-shape recognition suggests that the visual context in which a body is encountered deeply affects its perceptual analysis.
Parameter tuning differentiates granule cell subtypes enriching the repertoire of retransmission properties at the cerebellum input stage
Authors: Masoli Stefano , Tognolina Marialuisa , Laforenza Umberto , Moccia Francesco , D’Angelo Egidio
Published: May 2019

The cerebellar granule cells (GrCs) form an anatomically homogeneous neuronal population which, in its canonical description, discharges regularly without adaptation. We show here that GrCs in fact generate diverse response patterns to current injection and synaptic activation, ranging from adaptation to acceleration of firing. Adaptation was predicted by parameter optimization in detailed GrC computational models based on the available knowledge on GrC ionic channels. The models also predicted that acceleration required the involvement of additional mechanisms. We found that yet unrecognized TRPM4 currents in accelerating GrCs could specifically account for firing acceleration. Moreover, adapting GrCs were better in transmitting high-frequency mossy fiber (MF) bursts over a background discharge than accelerating GrCs. This implied that different electroresponsive patterns corresponded to specific synaptic properties reflecting different neurotransmitter release probability. The correspondence of pre- and post-synaptic properties generated effective MF-GrC transmission channels, which could enrich the processing of input spike patterns and enhance spatio-temporal recoding at the cerebellar input stage.
Animal model and therapeutic prospects for left ventricular hypertrophy and associated renal complication
Authors: Ahmad Ashfaq , Riaz Zainab , Sattar Munavvar Abdul , Khan Safia Akhtar , John Edward James , Arshad Sumbal , Shah Syed Tahir Abbas , Rafiq Muhammad Arshad , Azam Maleeha , Qamar Raheel
Published: May 2019

Cardiac and renal dysfunction often co-occur and considerably worsen the prognosis leading to difficulty in therapy in left ventricular hypertrophy (LVH). The aim of this study was to elucidate changes in expression of human ortholog genes of hypertension, vascular and cardiac remodeling and hypertensive nephropathy phenotypes under normal, disease and gasotransmitter, H2S (hydrogen sulphide) and NO (nitric oxide) and combined (H2S+NO), treatment of rat myocardium and renal tissues. LVH rat models were generated and were treated with H2S and NO. Relative gene expression was quantified. Heart and renal physical indices were significantly modified under individual as well as combined H2S+NO treatment in control and LVH rats. Expression analysis revealed, hypertension, vascular remodeling genes ACE, TNFα and IGF1, mRNAs to be significantly increased (P<0.05) in myocardia and kidneys of LVH rats, while individual and combined H2S+NO treatment reduced gene expression to normal/near to normal values. The cardiac remodeling genes MYH7, TGFβ, SMAD4 and BRG1 expression were significantly up-regulated (P<0.05) in the myocardia of LVH and combined H2S+NO treatment, which recovered the normal/near to normal expression more effectively as compared to individual treatments. Interestingly, individual as well as combined H2S and NO treatment significantly decreased PKD1 expression in renal tissue, which was significantly up-regulated in LVH rats (P<0.05). The reduction in hemodynamic parameters and cardiac indices as well as alteration in gene expression on treatment in LVH rat model indicates important therapeutic potential of combined treatment with H2S+NO gasotransmitters in hypertension and cardiac hypertrophy associated with renal complications.
Computational simulation of the reactive oxygen species and redox network in the regulation of chloroplast metabolism
Authors: Gerken Melanie , Kakorin Sergej , Chibani Kamel , Dietz Karl-Josef
Published: May 2019

Cells contain a thiol redox regulatory network to coordinate metabolic and developmental activities with exogenous and endogenous cues. This network controls the redox state and activity of many target proteins. Electrons are fed into the network from metabolism and reach the target proteins via redox transmitters such as thioredoxin (TRX) and NADPH-dependent thioredoxin reductases (NTR). Electrons are drained from the network by reactive oxygen species (ROS) through thiol peroxidases, e.g., peroxiredoxins (PRX). Mathematical modeling promises access to quantitative understanding of the network function and was implemented for the photosynthesizing chloroplast by using published kinetic parameters combined with fitting to known biochemical data. Two networks were assembled, namely the ferredoxin (FDX), FDX-dependent TRX reductase (FTR), TRX, fructose-1,6-bisphosphatase pathway with 2-cysteine PRX/ROS as oxidant, and separately the FDX, FDX-dependent NADP reductase (FNR), NADPH, NTRC-pathway for 2-CysPRX reduction. Combining both modules allowed drawing several important conclusions of network performance. The resting H2O2 concentration was estimated to be about 30 nM in the chloroplast stroma. The electron flow to metabolism exceeds that into thiol regulation of FBPase more than 7000-fold under physiological conditions. The electron flow from NTRC to 2-CysPRX is about 5.46-times more efficient than that from TRX-f1 to 2-CysPRX. Under severe stress (30 μM H2O2) the ratio of electron flow to the thiol network relative to metabolism sinks to 1:251 whereas the ratio of electron flow from NTRC to 2-CysPRX and TRX-f1 to 2-CysPRX rises up to 1:80. Thus, the simulation provides clues on experimentally inaccessible parameters and describes the functional state of the chloroplast thiol regulatory network.

Authors summary

The state of the thiol redox regulatory network is a fundamental feature of all cells and determines metabolic and developmental processes. However, only some parameters are quantifiable in experiments. This paper establishes partial mathematical models which enable simulation of electron flows through the regulatory system. This in turn allows for estimating rates and states of components of the network and to tentatively address previously unknown parameters such as the resting hydrogen peroxide levels or the expenditure of reductive power for regulation relative to metabolism. The establishment of such models for simulating the performance and dynamics of the redox regulatory network is of significance not only for photosynthesis but also, e.g., in bacterial and animal cells exposed to environmental stress or pathological disorders.
Immune state networks of wild and laboratory mice
Authors: Fonseca dos Reis Elohim , Viney Mark , Masuda Naoki
Published: May 2019

The mammalian immune system protects individuals from infection and disease. It is a complex system of interacting cells and molecules and extensive work, principally with laboratory mice, has investigated its function. Wild and laboratory animals lead very different lives, and this is reflected in there being substantial immunological differences between them. Here we use network analyses to study a unique data set of 120 immune measures of wild and laboratory mice, where immune measures define nodes and correlations of immune measures across individual mice define edges between immune measures. To date, there has only been very limited network analyses of the immune system, which is surprising because such analyses may be important to better understand its organisation and functionality. We found that the immunological networks of wild and laboratory mice were similar in some aspects of their mesoscale structure, particularly concerning cytokine response communities. However, we also identified notable differences in node membership of network communities between the wild and laboratory networks, pointing to how the same immune system acts and interacts differently in wild and in laboratory mice. These results show the utility of network analysis in understanding immune responses and also the importance of studying wild animals in additional to laboratory animals.

Author summary

The mammalian immune system is a complex system that protects individuals from infection and disease. Most of our understanding of the immune system comes from studies of laboratory animals, particularly mice. However, wild and laboratory animals lead very different lives, potentially leading to substantial immunological differences between them and so possibly limiting the utility of laboratory animals as informative model systems. As a complex interacting set of cells and molecules, the immune system is a biological network. Therefore, we used network analyses to study the immune system, specifically a unique data set of immune measures of wild and laboratory mice, where 120 different immune measures define nodes of the network. We found that the networks of wild and laboratory mice were similar in some aspects of their grouping structure, particularly concerning communities of nodes of cytokine responses. However, we also identified notable differences in node membership of communities between the wild and laboratory networks, pointing to how the same immune system behaves differently in wild and in laboratory mice. These results show the utility of network analysis in understanding immune responses and also the importance of studying wild animals in addition to laboratory animals.
Probing disorder in high-pressure cubic tin (IV) oxide: a combined X-ray diffraction and absorption study
Authors: Sneed Daniel , Kearney John S. C. , Smith Dean , Smith Jesse S. , Park Changyong , Salamat Ashkan
Published: May 2019

The transparent conducting oxide, SnO2, is a promising optoelectronic material with predicted tailorable properties via pressure-mediated band gap opening. While such electronic properties are typically modeled assuming perfect crystallinity, disordering of the O sublattice under pressure is qualitatively known. Here a quantitative approach is thus employed, combining extended X-ray absorption fine-structure (EXAFS) spectroscopy with X-ray diffraction, to probe the extent of Sn—O bond anharmonicities in the high-pressure cubic (Pa\bar{3}) SnO2 – formed as a single phase and annealed by CO2 laser heating to 2648 ± 41 K at 44.5 GPa. This combinational study reveals and quantifies a large degree of disordering in the O sublattice, while the Sn lattice remains ordered. Moreover, this study describes implementation of direct laser heating of non-metallic samples by CO2 laser alongside EXAFS, and the high quality of data which may be achieved at high pressures in a diamond anvil cell when appropriate thermal annealing is applied.
Crystal structure of poly[tetra-μ-chlorido-tetrachloridobis(μ3-4,4′-bi-1,2,4-triazole-κ3
N
1:N
2:N
1′)(μ-4,4′-bi-1,2,4-triazole-κ3
N
1:N
1′)tetracopper(II)]
Authors: Domasevitch Kostiantyn V. , Lysenko Andrey B.
Published: May 2019

The title Cu2+–chloride coordination polymer with the 4,4′-bi-1,2,4-triazole ligand (btr), [Cu4Cl8(C4H6N6)3]
n
, crystallizes in the non-centrosymmetric orthorhombic space group Fdd2. The two independent Cu2+ cations adopt distorted square-pyramidal geometries with {Cl2N2+Cl} coordination polyhedra. The metal atoms are bridged by μ-Cl anions forming left- and right-handed helical chains of sequence [–(μ-Cl)CuCl–]
n
along the c-axis direction. In the perpendicular directions, the btr ligands act in μ- and μ
3– coordination modes in a 2:3 ratio. The μ-btr bridges connect neighboring helices of the same handedness, whereas the μ
3-btr ligands link the helices of opposite handedness, leading to a racemic three-dimensional framework. The structure is consolidated by weak C—H...Cl and C—H...N interactions.
(E)-N′-Hydroxy-N,N-dimethyl-2-(3-nitrophenyl)acetimidamide
Authors: Ruan Yao , Zhao Hui
Published: May 2019

In the crystal of the title compound, C10H13N2O3, inversion dimers linked by pairs of N—H...O hydrogen bonds generate R
2
2(6) loops. The dimers are linked by weak C—H...O and C—H...π interactions, resulting in a three-dimensional network. A short NO2...NO2 contact [3.107 (2) Å] is also seen.
2-Amino-5,5-dimethylthiazol-4(5H)-one
Authors: Josey Daniel , Shank Nathaniel , Padgett Clifford W.
Published: May 2019

Our work exploring the synthesis and optimization of increasingly hindered thiols led to the synthesis and crystal structure determination of the title compound, C5H8N2OS, a dimethly-substituted 4-thiazolidinone. The molecular packing exhibits a herringbone pattern with the zigzag running along the b-axis direction; the compound crystallizes as chains of hydrogen-bonded dimers formed by N—H...N hydrogen bonds, which build centrosymmetric R
2
2(8) ring motifs in the crystal.
A development process for extending buildings vertically – based on a case study of four extended buildings
Authors: Sundling Rikard
Published: May 2019

Purpose

The purpose of the study, upon which this paper is based, was to contribute an improved understanding of the vertical extension of buildings, by presenting a development process for its implementation in which the key aspects to consider when planning such extensions are highlighted.

Design/methodology/approach

The approach is based on linking the diffusion of innovation together with case study research to stimulate further development in vertically extending buildings. Four cases of vertically extended buildings in Sweden were selected for the study.

Findings

The development process highlights seven key areas for decisions when planning a vertical extension. These areas are: opportunities for vertical extension; strategies for implementation; detailed planning process; concept development; evaluation; building permit; and procurement. The development processes and lessons learnt from each case are presented, covering both success and failure.

Research limitations/implications

The research is based on four cases of vertically extended buildings. The findings offer valuable insights into the development process which should provide the research community with an improved understanding of the challenges faced.

Practical implications

The findings will help planners, housing owners, housing developers and facility managers better understand the conditions that favour successful implementation of vertical extensions.

Originality/value

The paper provides the reader with an understanding of the challenges faced in the vertical extension of a building and the means of overcoming them to create a simplified development process.
Actions for relationship value: a mission impossible?
Authors: Munksgaard Kristin B. , Frandsen Kirsten
Published: May 2019

Purpose

The form and content of relationship value dominates the literature. This paper contributes by studying companies’ actions based on their value perceptions, a field which has attracted less attention. Scholars advocate more studies on how companies’ value perceptions shape actions in relationships and how this leads to outcomes.

Design/methodology/approach

A longitudinal critical case study of a customer/supplier relationship constitutes the empirical basis of the paper. Interviews and observation studies were conducted over a period of three years, giving access to special insight into the actors’ value perceptions and related actions.

Findings

Value perceptions shape actions performed individually, jointly or in the wider network. Moreover, misperceptions of the counterparty’s value perceptions may result in a maelstrom of interactions with no specific value outcome. Acting based on value perceptions is a complex matter due to its evolving nature, which leads to development becoming a value driver.

Research limitations/implications

The interdependencies between different value perceptions and their relational value drivers have special effects on actions and outcomes, also, value in actions needs to be studied.

Practical implications

Management needs to explore value from different perspectives to understand the counterparty’s value perceptions and communicate own perceptions. It is not sufficient to create value based on one value driver. Instead, it is vital to be able to connect value drivers to balance and prioritise relevant actions.

Originality/value

This paper stands out as one of the first contributions to relationship value literature that addresses and analyses value from both a customer perspective and a supplier perspective in a dyadic business relationship.
Knowledge management, the missing piece in the 2030 agenda and SDGs puzzle
Authors: Barrantes Briceño Christian Eric , Almada Santos Fernando César
Published: May 2019

Purpose

This paper aims to analyze some knowledge management (KM) frameworks that sustainable development goals (SDGs) can apply to such a challenging implementation.

Design/methodology/approach

To accomplish this, a systematic scientific literature review was carried out about the KM concept. Searching, analyzing and collecting different KM frameworks were crossed and compared to achieve a standard KM framework list, based on the most important and relevant information collected.

Findings

The study outlines how and which KM frameworks may be applied in an effort to reach the 2030 Agenda for Sustainable Development and SDGs, so it can overcome the barriers and pitfalls related to the knowledge management use.

Research limitations/implications

The paper shows some SDG areas that deserve future attention and deep implementation with KM frameworks.

Originality/value

With the enormous potential and vision of the sustainable development goals (SDGs), there is a barrier in its progress and development: the knowledge use, in both the local knowledge aspects and general knowledge management. This paper creates a Knowledge Management Excellence Model (KMEM) linked to SDGs, which will help and promote its use to educate and involve all those interested in meeting these goals.
Ownership and control over publicly accessible platform data
Authors: Scassa Teresa
Published: May 2019

Purpose

The purpose of this paper is to examine how claims to “ownership” are asserted over publicly accessible platform data and critically assess the nature and scope of rights to reuse these data.

Design/methodology/approach

Using Airbnb as a case study, this paper examines the data ecosystem that arises around publicly accessible platform data. It analyzes current statute and case law in order to understand the state of the law around the scraping of such data.

Findings

This paper demonstrates that there is considerable uncertainty about the practice of data scraping, and that there are risks in allowing the law to evolve in the context of battles between business competitors without a consideration of the broader public interest in data scraping. It argues for a data ecosystem approach that can keep the public dimension issues more squarely within the frame when data scraping is judicially considered.

Practical implications

The nature of some sharing economy platforms requires that a large subset of their data be publicly accessible. These data can be used to understand how platform companies operate, to assess their compliance with laws and regulations and to evaluate their social and economic impacts. They can also be used in different kinds of data analytics. Such data are therefore sought after by civil society organizations, researchers, entrepreneurs and regulators. This paper considers who has a right to control access to and use of these data, and addresses current uncertainties in how the law will apply to scraping activities, and builds an argument for a consideration of the public interest in data scraping.

Originality/value

The issue of ownership/control over publicly accessible information is of growing importance; this paper offers a framework for approaching these legal questions.