bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA-194 promotes lineage plasticity in advanced prostate cancer
Authors: Fernandes Rayzel C. , Toubia John , Townley Scott , Hanson Adrienne R. , Dredge B. Kate , Pillman Katherine A , Bert Andrew G. , Iggo Richard , Das Rajdeep , Obinata Daisuke ,   MURAL investigators, Sandhu Shahneen , Risbridger Gail P. , Taylor Renea A. , Lawrence Mitchell G. , Butler Lisa M. , Zoubeidi Amina , Gregory Philip A. , Tilley Wayne D. , Hickey Theresa E. , Goodall Gregory J. , Selth Luke A.
Published: September 2019

MicroRNA-194 (miR-194) promotes prostate cancer metastasis, but the precise molecular mechanisms by which it achieves this are unknown. Here, by integrating Argonaute high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (Ago-HITS-CLIP) with RNA sequencing and exon-intron split analysis, we defined a 163-gene miR-194 “targetome” in prostate cancer. These target genes were predominantly down-regulated through canonical 3’UTR recognition sites and were enriched within pathways involved in cytoskeletal organisation and cell movement. In clinical prostate cancer samples, miR-194 activity was inversely correlated with the androgen receptor (AR) signalling axis. At a mechanistic level, this inverse correlation was explained by down-regulation of miR-194 expression by AR. Accordingly, miR-194 expression and activity was significantly elevated in neuroendocrine prostate cancer (NEPC), an aggressive AR-independent disease subtype. MiR-194 enhanced the transdifferentiation of prostate adenocarcinoma cells to a neuroendocrine-like state, at least in part by targeting FOXA1, a transcription factor with a key role in maintaining the prostate epithelial lineage. Importantly, a miR-194 inhibitor effectively inhibited the growth of cell lines and patient-derived organoids with neuroendocrine features. Overall, our study reveals a novel post-transcriptional mechanism regulating the plasticity of prostate cancer cells and provides a rationale for targeting miR-194 in this NEPC.
Aβ(1-42) tetramer and octamer structures reveal edge pores as a mechanism for membrane damage
Authors: Ciudad Sonia , Puig Eduard , Botzanowski Thomas , Meigooni Moeen , Arango Andres S. , Do Jimmy , Mayzel Maxim , Bayoumi Mariam , Chaignepain Stéphane , Maglia Giovanni , Cianferani Sarah , Orekhov Vladislav , Tajkhorshid Emad , Bardiaux Benjamin , Carulla Natàlia
Published: September 2019

The formation of amyloid-beta (Aβ) oligomer pores in the membrane of neurons has been proposed as the means to explain neurotoxicity in Alzheimer’s disease (AD). It is therefore critical to characterize Aβ oligomer samples in membrane-mimicking environments. Here we present the first three-dimensional structure of an Aβ oligomer formed in dodecyl phosphocholine (DPC) micelles, namely an Aβ(1-42) tetramer. It comprises a β-sheet core made of six β-strands, connected by only two β-turns. The two faces of the β-sheet core are hydrophobic and surrounded by the membrane-mimicking environment. In contrast, the edges of the core are hydrophilic and are solvent-exposed. By increasing the concentration of Aβ(1-42), we prepared a sample enriched in Aβ(1-42) octamers, formed by two Aβ(1-42) tetramers facing each other forming a β-sandwich structure. Notably, samples enriched in Aβ(1-42) tetramers and octamers are both active in lipid bilayers and exhibit the same types of pore-like behaviour, but they show different occurrence rates. Remarkably, molecular dynamics simulations showed a new mechanism of membrane disruption in which water and ion permeation occurred through lipid-stabilized pores mediated by the hydrophilic residues located on the core β-sheets edges of the Aβ(1-42) tetramers and octamers.
The L-alanosine gene cluster encodes a pathway for diazeniumdiolate biosynthesis
Authors: Ng Tai L. , McCallum Monica E. , Zheng Christine R. , Wang Jennifer X. , Wu Kelvin J. Y. , Balskus Emily P.
Published: September 2019

N-nitroso-containing natural products are bioactive metabolites with antibacterial and anticancer properties. In particular, compounds containing the diazeniumdiolate (N-nitrosohydroxylamine) group display a wide range of bioactivities ranging from cytotoxicity to metal chelation. Despite the importance of this structural motif, knowledge of its biosynthesis is limited. Herein, we describe the discovery of a biosynthetic gene cluster in Streptomyces alanosinicus ATCC 15710 responsible for producing the diazeniumdiolate natural product L-alanosine. Gene disruption and stable isotope feeding experiments identified essential biosynthetic genes and revealed the nitrogen source of the N-nitroso group. Additional biochemical characterization of the biosynthetic enzymes revealed that the non-proteinogenic amino acid L-2,3-diaminopropionic acid (L-Dap) is synthesized and loaded onto a peptidyl carrier protein (PCP) domain in L-alanosine biosynthesis, which we propose may be a mechanism of handling unstable intermediates generated en route to the diazeniumdiolate. This research framework will facilitate efforts to determine the biochemistry of diazeniumdiolate formation.
Leveraging genome-wide data to investigate differences between opioid usevs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium
Authors: Polimanti Renato , Walters Raymond K. , Johnson Emma C. , McClintick Jeanette N. , Adkins Amy E. , Adkins Daniel E. , Bacanu Silviu-Alin , Bierut Laura J. , Bigdeli Tim B. , Brown Sandra , Bucholz Kathy , Copeland William E. , Costello E. Jane , Degenhardt Louisa , Farrer Lindsay A , Foroud Tatiana M. , Fox Louis , Goate Alison M. , Grucza Richard , Hack Laura M. , Hancock Dana B. , Hartz Sarah M. , Heath Andrew C. , Hewitt John K. , Hopfer Christian J. , Johnson Eric O. , Kendler Kenneth S. , Kranzler Henry R. , Krauter Ken , Lai Dongbing , Madden Pamela A. F. , Martin Nicholas G. , Maes Hermine H. , Nelson Elliot C. , Peterson Roseann E. , Porjesz Bernice , Riley Brien P. , Saccone Nancy , Stallings Michael , Wall Tamara , Webb Bradley T. ,   Leah Wetherill the Psychiatric Genomics Consortium Substance Use Disorders Workgroup, Edenberg Howard J. , Agrawal Arpana , Gelernter Joel
Published: September 2019

To provide novel insights into the biology of opioid dependence (OD) and opioid use (i.e., exposure, OE), we completed a genome-wide analysis comparing up to 4,503 OD cases, 4,173 opioid-exposed controls, and 32,500 opioid-unexposed controls. Among the variants identified, rs9291211 was associated with OE (a comparison of exposed vs. unexposed controls; z=-5.39, p=7.2×10−8). This variant regulates the transcriptomic profiles ofSLC30A9andBEND4in multiple brain tissues and was previously associated with depression, alcohol consumption, and neuroticism. A phenome-wide scan of rs9291211 in the UK Biobank (N>360,000) found association of this variant with propensity to use dietary supplements (p=1.68×10−8). With respect to the same OE phenotype in the gene-based analysis, we identifiedSDCCAG8(z=4.69, p=10−6), which was previously associated with educational attainment, risk-taking behaviors, and schizophrenia. In addition, rs201123820 showed a genome-wide significant difference between OD cases and unexposed controls (z=5.55, p=2.9×10−8) and a significant association with musculoskeletal disorders in the UK Biobank (p=4.88×10−7). A polygenic risk score (PRS) based on a GWAS of risk-tolerance (N=466,571) was positively associated with OD (OD cases vs. unexposed controls, p=8.1×10−5; OD cases vs. exposed controls, p=0.054) and OE (exposed controls vs. unexposed controls, p=3.6×10−5). A PRS based on a GWAS of neuroticism (N=390,278) was positively associated with OD (OD cases vs. unexposed controls, p=3.2×10−5; OD cases vs. exposed controls, p=0.002) but not with OE (p=0.671). Our analyses highlight the difference between dependence and exposure and the importance of considering the definition of controls (exposed vs. unexposed) in studies of addiction.
RNA Helicase DDX5 Negatively Regulates Wnt Signaling and Hepatocyte Reprogramming in Hepatitis B Virus-related Hepatocellular Carcinoma
Authors: Mani Saravana Kumar Kailasam , Cui Zhibin , Yan Bingyu , Utturkar Sagar , Foca Adrien , Fares Nadim , Durantel David , Lanman Nadia , Merle Philippe , Kazemian Majid , Andrisani Ourania
Published: September 2019

Background and Aims

RNA helicase DEAD box protein 5 (DDX5) is downregulated during hepatitis B virus (HBV) replication, and associates with poor prognosis HBV-related hepatocellular carcinoma (HCC). The aim of this study is to determine the mechanism and significance of DDX5 downregulation for HBV-driven HCC.

Approach & Results

We used established cellular models of HBV replication, HBV infection, as well as HBV-related liver tumors. HBV replicating DDX5 knockdown hepatocytes were analyzed by RNAseq; differentially expressed genes were validated by qRT-PCR, and bioinformatic analyses of HCCs from The Cancer Genome Atlas. Our results show reduced expression of DDX5 in HCCs of all etiologies is associated with poor survival. In HBV replicating hepatocytes, downregulation of DDX5 is mediated by miR17∼92 and miR106b∼25, induced by HBV infection. Increased expression of these miRNAs was quantified in HBV-associated HCCs expressing a hepatic cancer stem cell (hCSC)-like gene signature and reduced DDX5 mRNA, suggesting a role for DDX5 in hCSC formation. Interestingly, DDX5 knockdown in HBV replicating hepatocyte cell lines resulted in hepatosphere formation, sorafenib and cisplatin resistance, Wnt signaling activation and pluripotency gene expression, all characteristics of hCSCs. Moreover, DDX5 knockdown increased viral replication. RNA-seq analyses of HBV-replicating DDX5 knockdown cells, identified enhanced expression of key genes of the Wnt/β-catenin pathway, including Frizzled7 (FZD7) and Matrix Metallopeptidase7 (MMP7), indicative of Wnt signaling activation. Clinically, elevated FZD7 expression correlates with poor patient survival. Importantly, inhibitors to miR17∼92 and miR106b∼25 restored DDX5 levels and suppressed both Wnt/β-catenin activation and viral replication.

Conclusion

DDX5 is a negative regulator of Wnt signaling and hepatocyte reprogramming in HCCs. Restoration of DDX5 levels in HBV-infected patients can exert both antitumor and antiviral effects.
Ancient DNA reconstructs the genetic legacies of pre-contact Puerto Rico communities
Authors: Nieves-Colón Maria A. , Pestle William J. , Reynolds Austin W. , Llamas Bastien , de la Fuente Constanza , Fowler Kathleen , Skerry Katherine M. , Crespo-Torres Edwin , Bustamante Carlos D. , Stone Anne C.
Published: September 2019

Indigenous peoples have occupied the island of Puerto Rico since at least 3000 B.C. Due to the demographic shifts that occurred after European contact, the origin(s) of these ancient populations, and their genetic relationship to present-day islanders, are unclear. We use ancient DNA to characterize the population history and genetic legacies of pre-contact Indigenous communities from Puerto Rico. Bone, tooth and dental calculus samples were collected from 124 individuals from three pre-contact archaeological sites: Tibes, Punta Candelero and Paso del Indio. Despite poor DNA preservation, we used target enrichment and high-throughput sequencing to obtain complete mitochondrial genomes (mtDNA) from 45 individuals and autosomal genotypes from two individuals. We found a high proportion of Native American mtDNA haplogroups A2 and C1 in the pre-contact Puerto Rico sample (40% and 44%, respectively). This distribution, as well as the haplotypes represented, support a primarily Amazonian South American origin for these populations, and mirrors the Native American mtDNA diversity patterns found in present-day islanders. Three mtDNA haplotypes from pre-contact Puerto Rico persist among Puerto Ricans and other Caribbean islanders, indicating that present-day populations are reservoirs of pre-contact mtDNA diversity. Lastly, we find similarity in autosomal ancestry patterns between pre-contact individuals from Puerto Rico and the Bahamas, suggesting a shared component of Indigenous Caribbean ancestry with close affinity to South American populations. Our findings contribute to a more complete reconstruction of pre-contact Caribbean population history and explore the role of Indigenous peoples in shaping the biocultural diversity of present-day Puerto Ricans and other Caribbean islanders.
Dissociating cholinergic influence on alertness and temporal attention in primates in a simple reaction time paradigm
Authors: Oláh Vilmos , Knakker Balázs , Trunk Attila , Lendvai Balázs , Hernádi István
Published: September 2019

The ability to promptly respond to behaviourally relevant events depends on both general alertness and phasic changes in attentional state driven by temporal expectations. Using a variable foreperiod simple reaction time (RT) task in four adult male rhesus macaques, we investigated the role of the cholinergic system in alertness and temporal expectation. Foreperiod-effects on RT reflect temporal expectation, while alertness is quantified as overall response speed. We measured these RT parameters under vehicle treatment and systemic administration of the muscarinic receptor antagonist scopolamine. We also investigated whether and to what extent the effects of scopolamine were reversed by donepezil, a cholinesterase inhibitor widely used for the treatment of dementia. In the control condition, RT showed a continuous decrease as the foreperiod duration increased, which clearly indicated the effect of temporal expectation on RT. This foreperiod effect was mainly detectable on the faster tail of the RT distribution and was eliminated by scopolamine. Furthermore, scopolamine treatment slowed down the average RT. Donepezil treatment was efficient on the slower tail of the RT distribution and improved scopolamine-induced impairments only on the average RT reflecting a general beneficial effect on alertness without any improvement in temporal expectation. The present results highlight the role of the cholinergic system in temporal expectation and alertness in primates and help delineate the efficacy and scope of donepezil and other cholinomimetic agents as cognitive enhancers in present and future clinical practice.
β-cells operate collectively to help maintain glucose homeostasis
Authors: Podobnik Boris , Korošak Dean , Klemen Maša Skelin , Stožer Andraž , Dolenšek Jurij , Rupnik Marjan Slak , Ivanov Plamen Ch. , Holme Petter , Jusup Marko
Published: September 2019

Residing in the islets of Langerhans in the pancreas, beta cells contribute to glucose homeostasis by managing the body’s insulin supply. A circulating hypothesis has been that healthy beta cells heavily engage in cell-to-cell communication to perform their homeostatic function. We provide strong evidence in favor of this hypothesis in the form of (i) a dynamical network model that faithfully mimics fast calcium oscillations in response to above-threshold glucose stimulation and (ii) empirical data analysis that reveals a qualitative shift in the cross-correlation structure of measured signals below and above the threshold glucose concentration. Combined together, these results point to a glucose-induced transition in beta-cell activity thanks to increasing coordination through gap-junctional signaling and paracrine interactions. The model further suggests how the conservation of entire cell-cell conductance, observed in coupled but not uncoupled beta cells, emerges as a collective phenomenon. An overall implication is that improving the ability to monitor beta-cell signaling should offer means to better understand the pathogenesis of diabetes mellitus.
Empirical evaluation of fused EEG-MEG source reconstruction. Application to auditory mismatch generators
Authors: Lecaignard Françoise , Bertrand Olivier , Caclin Anne , Mattout Jérémie
Published: September 2019

Since their introduction in the late eighties, Bayesian approaches for neuroimaging have opened the way to new powerful and quantitative analysis of brain data. Here, we apply this statistical framework to evaluate empirically the gain of fused EEG-MEG source reconstruction, compared to unimodal (EEG or MEG) one. Combining EEG and MEG information for source reconstruction has been consistently evidenced to enhance localization performances using simulated data. However, given considerable efforts to conduct simultaneous recordings, empirical evaluation becomes necessary to quantify the real information gain. And this is obviously not straightforward due to the ill-posedness of the inverse problem. Here, we consider Bayesian model comparison to quantify the ability of EEG, MEG and fused (EEG/MEG) inversions of individual data to resolve spatial source models. These models consisted in group-level cortical distributions inferred from real EEG, MEG and EEG/MEG brain responses. We applied this comparative evaluation to the timely issue of the generators of auditory mismatch responses evoked by unexpected sounds. These included the well-known Mismatch Negativity (MMN) but also earlier deviance responses. As expected, fused localization was evidenced to outperform unimodal inversions with larger model separability. The present methodology confirms with real data the theoretical interest of simultaneous EEG/MEG recordings and fused inversion to highly inform (spatially and temporally) source modeling. Precisely, a bilateral fronto-temporal network could be identified for both the MMN and early deviance response. Interestingly, multimodal inversions succeeded in revealing spatio-temporal details of the functional organization within the supratemporal plane that have not been reported so far, nor were visible here with unimodal inversions. The present refined auditory network could serve as priors for auditory modeling studies.
The effects of carnosine pretreatment on the inflammatory response and the PI3K/Akt signaling pathway following hypoxia-ischemia in neonatal rats
Authors: Zhang Xiangmin , Xia Lei , Huang Zhiheng , Xu Falin
Published: September 2019

An increasing number of studies have demonstrated that carnosine plays a neuroprotective role in many types of brain injury. We have previously shown that carnosine has both short-term and long-lasting neuroprotective effects in a hypoxia–ischemia(HI) rat model. In the mature brain, post-ischemia neuronal survival involves in activation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, whether the activation of PI3K/Akt pathway also plays an important role in the immature brain still remain unclear.The goal of this study is to detect the effection of carnosine on inflammation response following HI, further evidencing neuroprotection of carnosine. We measured total Akt, phospho-Akt (p-AKT) and tumor necrosis factor receptor 1 (TNFR1) protein levels by western blot assay and tumor necrosis factor-α (TNF-α) and TNFR1 mRNA expression using real-time RT-PCR. We found the carnosine-pretreated group had statistically significant downregulation of TNF-α mRNA levels 24 h after HI (P < 0.05). Similar results were observed when we measured TNFR1 mRNA levels both 24h and 72h after HI (P < 0.05). And the TNFR1 protein expression after HI was markedly decreased at 24 and 72 h post-HI in the carnosine-pretreated rats(P < 0.05). Nevertheless, the rats pretreated with carnosine showed a marked increase in p-Akt levels (P< 0.05). And the pro-apoptotic protein Bad was also examined using immunohistochemistry after 24 and 72 h of all groups. We found significantly fewer Bad-positive cells in the carnosine-pretreated group at each time point after HI (P < 0.05). These findings suggest that carnosine pretreatment inhibits the HI-induced inflammatory response, and neuroprotection mechanism of carnosine involved in activation of the PI3K/Akt signaling pathway.
A locked immunometabolic switch underlies TREM2 R47H loss of function in human iPSC--derived microglia
Authors: Piers Thomas M , Cosker Katharina , Mallach Anna , Johnson Gabriel Thomas , Guerreiro Rita , Hardy John , Pocock Jennifer M
Published: September 2019

Loss-of-function genetic variants oftriggering receptor expressed on myeloid cells 2 (TREM2)are linked with an enhanced risk of developing dementias. Microglia, the resident immune cell of the brain, express TREM2 and microglial responses are implicated in dementia pathways. In a normal surveillance state, microglia use oxidative phosphorylation for their energy supply, but rely on the ability to undergo a metabolic switch to glycolysis to allow them to perform rapid plastic responses. We investigated the role of TREM2 on microglial metabolic function in human patient iPSC-derived-microglia expressing loss of function variants in TREM2. We show that these TREM2 variant iPSC-microglia, including the Alzheimer’s disease R47H risk variant, exhibit significant metabolic deficits including a reduced mitochondrial respiratory capacity and an inability to perform a glycolytic immunometabolic switch. We determined that dysregulated PPARγ/p38MAPK signalling underlies the observed phenotypic deficits in TREM2 variants and that activation of these pathways can ameliorate the metabolic deficit in these cells and consequently rescue critical microglial cellular function such as β-Amyloid phagocytosis. These findings have ramifications for microglial focussed-treatments in AD.
Evaluation of six phase encoding based susceptibility distortion correction methods for diffusion MRI
Authors: Gu Xuan , Eklund Anders
Published: September 2019

Purpose

Susceptibility distortions impact diffusion MRI data analysis and is typically corrected during preprocessing. Correction strategies involve three classes of methods: registration to a structural image, the use of a fieldmap, or the use of images acquired with opposing phase encoding directions. It has been demonstrated that phase encoding based methods outperform the other two classes, but unfortunately, the choice of which phase encoding based method to use is still an open question due to the absence of any systematic comparisons.

Methods

In this paper we quantitatively evaluated six popular phase encoding based methods for correcting susceptibility distortions in diffusion MRI data. We employed a framework that allows for the simulation of realistic diffusion MRI data with susceptibility distortions. We evaluated the ability for methods to correct distortions by comparing the corrected data with the ground truth. Four diffusion tensor metrics (FA, MD, eigenvalues and eigenvectors) were calculated from the corrected data and compared with the ground truth. We also validated two popular indirect metrics using both simulated data and real data. The two indirect metrics are the difference between the corrected LR and AP data, and the FA standard deviation over the corrected LR, RL, AP and PA data.

Results

We found that DR-BUDDI and TOPUP offered the most accurate and robust correction compared to the other four methods using both direct and indirect evaluation metrics. EPIC and HySCO performed well in correcting b0 images but produced poor corrections for diffusion weighted volumes, and also they produced large errors for the four diffusion tensor metrics. We also demonstrate that the indirect metric (the difference between corrected LR and AP data) gives a different ordering of correction quality than the direct metric.

Conclusion

We suggest researchers to use DR-BUDDI or TOPUP for susceptibility distortion correction. The two indirect metrics (the difference between corrected LR and AP data, and the FA standard deviation) should be interpreted together as a measure of distortion correction quality. We also suggest that indirect metrics must be interpreted cautiously when evaluating methods for correcting susceptibility distortions in diffusion MRI data.
Molecular architecture of the DNA‐binding sites of the P‐loop ATPases MipZ and ParA fromCaulobacter crescentus
Authors: Refes Yacine , He Binbin , Corrales-Guerrero Laura , Steinchen Wieland , Panis Gaël , Viollier Patrick H. , Bange Gert , Thanbichler Martin
Published: September 2019

Two related P-loop ATPases, ParA and MipZ, mediate the spatiotemporal regulation of chromosome segregation and cell division inCaulobacter crescentus. Both of these proteins share the ability to form dynamic concentration gradients that control the positioning of regulatory targets within the cell. Their proper localization relies on their nucleotide-dependent cycling between a monomeric and a dimeric state, driven by interaction with the chromosome partitioning protein ParB, and on the ability of the dimeric species to associate non-specifically with the nucleoid. In this study, we use a combination of genetic screening, biochemical analysis and hydrogen/deuterium exchange mass spectrometry to identify the residues mediating the interaction of MipZ with DNA. Our results show that the DNA-binding activity of MipZ relies on a series of positively charged and hydrophobic residues lining both sides of the dimer interface. MipZ thus appears to associate with DNA in a sequence-independent manner through electrostatic interactions with the DNA phosphate backbone. In support of this hypothesis, chromatin immunoprecipitation analyses did not reveal any specific target sitesin vivo. When extending our analysis to ParA, we found that the architectures of the MipZ and ParA DNA-binding sites are markedly different, although their relative positions on the dimer surface and their mode of DNA binding are conserved. Importantly, bioinformatic analysis suggests that the same principles apply to other members of the P-loop ATPase family. ParA-like ATPases thus share common mechanistic features, although their modes of action have diverged considerably during the course of evolution.

SIGNIFICANCE

ParA-like P-loop ATPases are involved in a variety of cellular processes in bacteria, including chromosome and plasmid segregation, chemoreceptor and carboxysome positioning, and division site placement. Many members of this large protein family depend on the ability to bind non-specific DNA for proper function. Although previous studies have yielded insights in the DNA-binding properties of some ParA-like ATPases, a comprehensive view of the underlying mechanisms is still lacking. Here, we combine state-of-the-art cell biological, biochemical and biophysical approaches to localize the DNA-binding regions of the ParA-like ATPases MipZ and ParA fromCaulobacter crescentus. We show that the two proteins use the same interface and mode of action to associate with DNA, suggesting that the mechanistic basis of DNA binding may be conserved in the ParA-like ATPase family.
LITE-1 Dependent X-Ray Sensitivity in C. elegans
Authors: Cannon Kelli E. , Ranasinghe Meenakshi , Do Anhkhoa , Pierce H. Mariah , Millhouse Paul W. , Roychowdhury Ayona , Foulger Stephen , Dobrunz Lynn , Anker Jeffrey N. , Bolding Mark
Published: September 2019

We report the finding that C. elegans display X-ray avoidance behavior at high but well tolerated doses, and that this behavior appears to require LITE-1, a gustatory receptor that has been implicated in UV avoidance behavior. We recorded acute behavioral responses of wildtype worms to increasing intensities of X-ray stimulation and found a positive stimulation-response relationship. Mutant strains of worms with dysfunctional photoreceptor proteins LITE-1 and GUR-3 were assayed, and the X-ray avoidance response was found to be nearly absent in LITE-1 mutants but not GUR-3 mutants, suggesting a prominent role for LITE-1 in the detection of X-rays. These findings may be important for developing optogenetics tools to stimulate cells in deep tissue using X-rays, for understanding the mechanism of LITE-1 signaling, and for understanding how organisms may respond to radiation.
Tree congruence: quantifying similarity between dendrogram topologies
Authors: Vidovic Steven U.
Published: September 2019

Tree congruence metrics are typically global indices that describe the similarity or dissimilarity between dendrograms. This study principally focuses on topological congruence metrics that quantify similarity between two dendrograms and can give a normalised score between 0 and 1. Specifically, this article describes and tests two metrics the Clade Retention Index (CRI) and the MASTxCF which is derived from the combined information available from a maximum agreement subtree and a strict consensus. The two metrics were developed to study differences between evolutionary trees, but their applications are multidisciplinary and can be used on hierarchical cluster diagrams derived from analyses in science, technology, maths or social sciences disciplines. A comprehensive, but non-exhaustive review of other tree congruence metrics is provided and nine metrics are further analysed. 1,620 pairwise analyses of simulated dendrograms (which could be derived from any type of analysis) were conducted and are compared in Pac-man piechart matrices. Kendall’s tau-b is used to demonstrate the concordance of the different metrics and Spearman’s rho ranked correlations are used to support these findings. The results support the use of the CRI and MASTxCF as part of a suite of metrics, but it is recommended that permutation metrics such as SPR distances and weighted metrics are disregarded for the specific purpose of measuring similarity.
Crystal structure and molecular Hirshfeld surface analysis of acenaphthene derivatives obeying the chlorine–methyl exchange rule
Authors: Sribala R. , Indhumathi S. , Krishnakumar R.V. , Srinivasan N.
Published: September 2019

Instances of crystal structures that remain isomorphous in spite of some minor changes in their respective molecules, such as change in a substituent atom/group, can provide insights into the factors that govern crystal packing. In this context, an accurate description of the crystal structures of an isomorphous pair that differ from each other only by a chlorine–methyl substituent, viz. 5′′-(2-chlorobenzylidene)-4′-(2-chlorophenyl)-1′-methyldispiro[acenaphthene-1,2′-pyrrolidine-3′,3′′-piperidine]-2,4′′-dione, C34H28Cl2N2O2, (I), and its analogue 1′-methyl-5′′-(2-methylbenzylidene)-4′-(2-methylphenyl)dispiro[acenaphthene-1,2′-pyrrolidine-3′,3′′-piperidine]-2,4′′-dione, C36H34N2O2, (II), is presented. While there are two C—H...O weak intermolecular interactions present in both (I) and (II), the change of substituent from chlorine to methyl has given rise to an additional weak C—H...O intermolecular interaction that is relatively stronger than the other two. However, the presence of the stronger C—H...O interaction in (II) has not disrupted the validity of the chloro-methyl exchange rule. Details of the crystal structures and Hirshfeld analyses of the two compounds are presented.
Crystal structure and Hirshfeld surface analysis of 5-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamide
Authors: Asgarova Ayten R.
Published: September 2019

In the title compound, C24H31N3O2, the mean plane of the central pyrazole ring [r.m.s. deviation = 0.095 Å] makes dihedral angles of 11.93 (9) and 84.53 (8)°, respectively, with the phenyl and benzene rings. There is a short intramolecular N—H...N contact, which generates an S(5) ring motif. In the crystal, pairs of N—H...O hydrogen bonds link inversion-related molecules into dimers, generating an R
2
2(8) ring motif. The Hirshfeld surface analysis indicates that the most significant contribution involves H...H contacts of 68.6%
A portrait of workplace discrimination in Italy: empirical evidence from a nationwide survey
Authors: Palumbo Rocco , Manna Rosalba
Published: September 2019

Purpose

Workplace discrimination negatively affects the functioning of organizations. Scholars have generally focused their attention on specific forms of prejudiced treatment at work as well as on particular groups of discriminated employees. Conversely, studies investigating the multifacetedness of this phenomenon are sporadic. The purpose of this article is to contribute to the advancement of the scientific knowledge about workplace discrimination showing a full-fledged portrait of this phenomenon in Italy.

Design/methodology/approach

Secondary data about self-reported experiences of workplace discrimination of a large sample of Italian people were collected and run in a logistic regression model. Five forms of discrimination at work were taken into account: prejudiced job design and work allocation; discriminatory use of promotion and awards; wage differentials; unjustified increased workload; and mismanagement of HRM instruments.

Findings

More than a fifth of respondents perceived at least one form of workplace discrimination. Different types of prejudiced treatment were triggered by distinctive socio-demographic and work-related factors. People who were unemployed at the moment of the interview were consistent in claiming that they suffered from all the forms of workplace discrimination. Former employees who underwent a work-family conflict were more likely to suffer from iniquitous treatment at work.

Research limitations/implications

The occurrence of workplace discrimination was not objectively assessed. Besides, since only Italian people were included in this study, the findings are not generalizable at the international level.

Originality/value

This article provides some insights to inspire policy and management interventions intended to prevent and/or curb the occurrence workplace discrimination.
Do new ventures explore, exploit or both? A case-based analysis of six innovative Italian start-ups
Authors: Rippa Pierluigi , Ponsiglione Cristina , Bocanet Anca , Capaldo Guido , Zollo Giuseppe
Published: September 2019

Purpose

The purpose of this paper is to contribute to the debate on exploration–exploitation trade-off in the context of new ventures creation, where, particularly at the empirical level, there is a limited understanding of whether and how this trade-off is achieved and how start-ups performances are affected by the way in which they face the exploration–exploitation dilemma.

Design/methodology/approach

A qualitative case study approach has been adopted as a methodology to conduct the research. Six Italian innovative start-ups were selected and analyzed through in-depth interviews with founders and data collection to understand whether and how start-ups adopt exploration and exploitation solutions to face critical events in their business lives.

Findings

The most evident result of this study is that start-ups adopt more frequently a temporal separation of exploration and exploitation activities as the preferred mode for balancing learning and innovation tension. They do not seem to exhibit a defined or a common path in the way they realize the temporal separation between exploration and exploitation. Instead, they mostly oscillate. The ambidextrous solution is selected in only a few cases and not consecutively. The pre-entry knowledge profile seems to influence the choice of start-ups at the beginning of their lives.

Practical implications

This research has implications for the whole start-up’s ecosystem, comprising incubators/accelerators, advisors, intermediaries, venture capitalists, new venture founders and policymakers. For example, by knowing the typology of knowledge and competence gaps start-ups usually aim to fill when they face particular events, intermediaries (such as incubators) could better plan initiatives and strategies supporting new ventures in the process of growth and stabilization. Furthermore, the venture capitalists can benefit from this research, by planning specific interventions for each critical event based on specific resources and competencies gaps and guiding for more promising start-ups.

Originality/value

This paper presents a novel application of entrepreneurial learning approach in the context of new venture creation. To reach this aim, a classification of exploration/exploitation solutions has been developed.
Social isolation and loneliness among immigrant and refugee seniors in Canada: a scoping review
Authors: Johnson Shanthi , Bacsu Juanita , McIntosh Tom , Jeffery Bonnie , Novik Nuelle
Published: September 2019

Purpose

Social isolation and loneliness are global issues experienced by many seniors, especially immigrant and refugee seniors. Guided by the five-stage methodological framework proposed by Arksey and O’Malley and more recently Levac, Colquhoun and O’Brien, the purpose of this paper is to explore the existing literature on social isolation and loneliness among immigrant and refugee seniors in Canada.

Design/methodology/approach

The authors conducted a literature search of several databases including: PubMed; MEDLINE; CINAHL; Web of Science; HealthStar Ovid; PschyInfo Ovid; Social Services Abstracts; AgeLine; Public Health Database, Google Scholar and Cochrane Library. In total, 17 articles met the inclusion criteria.

Findings

Based on the current literature five themes related to social isolation and loneliness emerged: loss; living arrangements; dependency; barriers and challenges; and family conflict.

Research limitations/implications

Given the increasing demographic of aging immigrants in Canada, it is useful to highlight existing knowledge on social isolation and loneliness to facilitate research, policy and programs to support this growing population.

Practical implications

The population is aging around the world and it is also becoming increasingly diverse particularly in the high-income country context. Understanding and addressing social isolation is important for immigrant and refugee seniors, given the sociocultural and other differences.

Social implications

Social isolation is a waste of human resource and value created by seniors in the communities.

Originality/value

The paper makes a unique contribution by focusing on immigrant and refugee seniors.
Platforms in the peer-to-peer sharing economy
Authors: Wirtz Jochen , So Kevin Kam Fung , Mody Makarand Amrish , Liu Stephanie Q. , Chun HaeEun Helen
Published: September 2019

Purpose

The purpose of this paper is to examine peer-to-peer sharing platform business models, their sources of competitive advantage, and the roles, motivations and behaviors of key actors in their ecosystems.

Design/methodology/approach

This paper uses a conceptual approach that is rooted in the service, tourism and hospitality, and strategy literature.

Findings

First, this paper defines key types of platform business models in the sharing economy anddescribes their characteristics. In particular, the authors propose the differentiation between sharing platforms of capacity-constrained vs capacity-unconstrained assets and advance five core properties of the former. Second, the authors contrast platform business models with their pipeline business model counterparts to understand the fundamental differences between them. One important conclusion is that platforms cater to vastly more heterogeneous assets and consumer needs and, therefore, require liquidity and analytics for high-quality matching. Third, the authors examine the competitive position of platforms and conclude that their widely taken “winner takes it all” assumption is not valid. Primary network effects are less important once a critical level of liquidity has been reached and may even turn negative if increased listings raise friction in the form of search costs. Once a critical level of liquidity has been reached, a platform’s competitive position depends on stakeholder trust and service provider and user loyalty. Fourth, the authors integrate and synthesize the literature on key platform stakeholders of platform businesses (i.e. users, service providers, and regulators) and their roles and motivations. Finally, directions for further research are advanced.

Practical implications

This paper helps platform owners, service providers and users understand better the implications of sharing platform business models and how to position themselves in such ecosystems.

Originality/value

This paper integrates the extant literature on sharing platforms, takes a novel approach in delineating their key properties and dimensions, and provides insights into the evolving and dynamic forms of sharing platforms including converging business models.
Team formulation in practice: forms, functions, and facilitators
Authors: Geach Nicole , De Boos Danielle , Moghaddam Nima
Published: September 2019

Purpose

Despite the popularity of team formulation, there is a lack of knowledge about workable implementation in practice. The purpose of this paper is twofold: first, to characterise team formulation, based upon examples from practice; and second, to identify factors perceived to support or obstruct workable implementation in practice.

Design/methodology/approach

An online survey recruited UK Clinical Psychologists (n=49) with experience in team formulation from a range of work contexts. Examples of team formulation in practice were analysed using both deductive and inductive framework analysis.

Findings

Four novel types of team formulation with different functions and forms are described: case review, formulating behaviour experienced as challenging, formulating the staff-service user relationship and formulating with the service-user perspective. A number of factors perceived to support and obstruct team formulation were identified including team distress, facilitating change, managing difference and informing practice. These were common across team formulation types.

Practical implications

The team formulation types identified could be used to standardise team formulation practice. Several common factors, including managing team distress, were identified as aiding workable implementation across team formulation types. Future research should investigate the key processes and links to outcomes of team formulation in practice.

Originality/value

This paper presents two original, practice-based and practice-informing frameworks: describing, first, novel forms and functions of team formulation and, second, the factors supporting and obstructing facilitation in practice. This paper is the first to highlight the common factors that seem to facilitate workable implementation of team formulation in practice.
Reception characteristics investigation and measurement of capacitive micromachined ultrasonic transducer
Authors: Wang Hongliang , Wang Xiangjun , He Changde , Xue Chenyang
Published: September 2019

Purpose

As a new type of ultrasonic transducer with significant advantages, capacitive micromachined ultrasonic transducer (CMUT) has good application prospect. The reception characteristic of the CMUT is one of the important factors determining the application effect. This paper aims to study the reception characteristics of CMUT.

Design/methodology/approach

In this paper, the state equation is deduced and the analysis model is established in SIMULINK environment based on the lumped parameter system model of the CMUT cell. Based on this analysis model, the influencing factors of CMUT reception characteristics are studied and investigated, and the time-domain and frequency-domain characteristics are investigated in detail.

Findings

The analysis results show that parameters directly affect the reception characteristics of the CMUT, such as direct current (DC) bias voltage, input sound pressure amplitude and frequency. At the same time, the measurement system is built and the reception characteristics are verified.

Originality/value

This paper provides an effective method for rapid analyzing the reception characteristics of CMUT. These results provide an important theoretical basis and reference for further optimization of CMUT structure design, and lay a good foundation for the practical application measurement.
Valuation of hotel property: issues and challenges
Authors: Majumdar Raju
Published: September 2019

Purpose

The purpose of this paper is to provide a practitioners’ perspective on the valuation models used for valuing hotel property and the challenges posed by traditional valuation models in their application and use. Set in the context of the Indian hospitality industry, the paper brings out the paradigm shifts that have taken place in recent years in the context of valuations. The paper also attempts to provide resolution to the issues and challenges raised.

Design/methodology/approach

This study assimilates data from senior finance professionals and by using semi-structured interviews, draws on a wide spectrum of hotels in India.

Findings

The findings suggest that the earnings-based models are largely followed in valuing hotel property in India. The major challenges encountered in the valuation process as highlighted by the respondents are related to (a) the growing uncertainty associated with projections of future earnings given the plethora of assumptions made at a micro and macro level, and (b) determination of an appropriate discounting factor for computing the present value of future cash flows.

Research limitations/implications

This paper generates useful qualitative information on existing practices in valuation in the Indian hospitality sector. The findings will be useful for hoteliers, policymakers and researchers in bringing forth the valuation challenges faced in the context of a developing economy and its characteristic institutional weaknesses. The findings of this paper may be furthered through appropriate and detailed quantitative analysis of primary and secondary data on the issues and challenges raised here.

Originality/value

This paper makes a sincere attempt to highlight the real challenges faced in valuing hotel properties and as such adds value to the existing literature.
The influencing role of social media in the consumer’s hotel decision-making process
Authors: Gupta Vikas
Published: September 2019

Purpose

This study aims to evaluate the role of social media on the hotel decision-making process of consumers during the evaluation stage of searching, identifying the alternatives and selecting a hotel in India. It will help the stakeholders in the hotel industry of India to make the social media platform more efficient for consumers by providing inputs on the factors consumers consider while making online hotel purchase.

Design/methodology/approach

This study involves an exploratory qualitative approach which includes 32 face-to-face, semi-structured, in-depth individual interviews with the social media platform users. The selection of interviewees for this study has been done on the basis of a non-random purposive sampling approach.

Findings

The findings reveal that social media plays an important role in affecting the way consumers search, decide and book hotels. It also suggests that social media helps consumers in collecting information about products and services, assessing alternatives and making their choices. It confirms that while negative facets exist, the positive benefits outweigh the negative aspects of using social media when selecting a hotel. The results also reveal the impact of circumstantial influence related to social media on hotel selection, on the basis of content source and the level of trust and accuracy in the content.

Practical implications

This study has some strategic implications for hospitality marketing and management related to a better understanding of the influence of social media on the hotel customer decision-making process. The study shows that a variety of social media with associated content sources and levels add to the complexity of hotel-related information search and decision behaviour.

Originality/value

The study makes a contribution by addressing the existing gaps and bridging the arena of consumer behaviour and social media literature in a hotel context and sheds light on how consumer decisions while selecting a hotel are influenced through social media. The core contribution is the generation of factors through in-depth interviews which are based on real-life scenarios relating to the influence of social media on hotel decision-making.