bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain states govern the spatio-temporal dynamics of resting state functional connectivity
Authors: Aedo-Jury Felipe , Schwalm Miriam , Hamzehpour Lara , Stroh Albrecht
Published: November 2019

Previously, using simultaneous task-free fMRI and optic-fiber-based neuronal calcium recordings in the anesthetized rat, we identified BOLD responses directly related to slow calcium waves, revealing a cortex-wide and spatially organized BOLD correlate (Schwalm et al. 2017). Here, with these bimodal recordings, we reveal two distinct brain states: persistent state, in which compartmentalized network activity was observed, including defined subsets such as the default mode network; and slow wave state, dominated by a cortex-wide component, suggesting a strong functional coupling of brain activity. In slow wave state we find a correlation between slow wave events and the strength of functional connectivity. These findings suggest that indeed down-up transitions of neuronal excitability drive cortex-wide functional connectivity. This study provides strong evidence that previously reported changes in functional connectivity are highly dependent on the brain’s current state and directly linked with cortical excitability and slow waves generation.
Doing nothing and what it looks like… Inactivity in fattening cattle
Authors: Hintze Sara , Maulbetsch Freija , Asher Lucy , Winckler Christoph
Published: November 2019

Animals kept in barren environments often show increased levels of inactivity and first studies indicate that inactive behaviour may reflect boredom or depression-like states. However, inactivity does not necessarily reflect negative welfare and can even be a sign of positive welfare, for example in terms of relaxation. To date, knowledge of how to reliably differentiate between positive and negative states associated with inactivity is scarce and methods to identify different forms of inactivity are thus warranted. To this end, we developed an Inactivity Ethogram including detailed information on the postures of different body parts (Standing/Lying, Head, Ears, Eyes, Tail) for fattening cattle, a farm animal category often kept in barren environments. The Inactivity Ethogram was applied to Austrian Fleckvieh heifers from intensive, semi-intensive and pasture-based husbandry systems. Three farms per husbandry system were visited twice; once in the morning and once in the afternoon to cover most of the daylight hours with our observations. During each visit, 16 focal animals were continuously observed for 15 minutes each (96 heifers per husbandry system, 288 in total). Moreover, the focal animals’ groups were video recorded to later determine the inactivity level on the group level. Group level and focal animal data were analysed with (generalised) linear mixed-effect models with husbandry system as fixed effect and (group nested in) farm visit nested in farm as random effects. Husbandry system did not affect group level inactivity or the time the different postures were adopted (with the exception of asymmetrical ears, which were more prevalent in intensive than in semi-intensive than in pasture systems). In addition to the analysis of the time the single postures were observed for, simultaneous occurrences of postures of different body parts (Standing/Lying, Head, Ears and Eyes) were analysed using the machine learning algorithm cspade to provide insight into co-occurring postures of inactivity. Frequently co-occurring postures were generally similar between husbandry systems, but with subtle differences. The most frequently observed combination in intensive and semi-intensive systems was Lying with Head up, Ears backwards and Eyes open whereas in pasture systems it was Lying with Head up, ears low and eyes closed. To conclude, both the Inactivity Ethogram (including the description of detailed postures) and the machine learning algorithm cspade (for identifying frequently co-occurring posture combinations) are promising tools to understand how combinations of postures may be used to distinguish between different affective states associated with inactivity.
Pan-cancer image-based detection of clinically actionable genetic alterations
Authors: Kather Jakob Nikolas , Heij Lara R. , Grabsch Heike I. , Kooreman Loes F. S. , Loeffler Chiara , Echle Amelie , Krause Jeremias , Muti Hannah Sophie , Niehues Jan M. , Sommer Kai A. J. , Bankhead Peter , Schulte Jefree J. , Cipriani Nicole A. , Ortiz-Brüchle Nadina , Patnaik Akash , Srisuwananukorn Andrew , Brenner Hermann , Hoffmeister Michael , van den Brandt Piet A. , Jäger Dirk , Trautwein Christian , Pearson Alexander T. , Luedde Tom
Published: November 2019

Precision treatment of cancer relies on genetic alterations which are diagnosed by molecular biology assays.1 These tests can be a bottleneck in oncology workflows because of high turnaround time, tissue usage and costs.2 Here, we show that deep learning can predict point mutations, molecular tumor subtypes and immune-related gene expression signatures3,4 directly from routine histological images of tumor tissue. We developed and systematically optimized a one-stop-shop workflow and applied it to more than 4000 patients with breast5, colon and rectal6, head and neck7, lung8,9, pancreatic10, prostate11 cancer, melanoma12 and gastric13 cancer. Together, our findings show that a single deep learning algorithm can predict clinically actionable alterations from routine histology data. Our method can be implemented on mobile hardware14, potentially enabling point-of-care diagnostics for personalized cancer treatment in individual patients.
A structure-based deep learning framework for protein engineering
Authors: Shroff Raghav , Cole Austin W. , Morrow Barrett R. , Diaz Daniel J. , Donnell Isaac , Gollihar Jimmy , Ellington Andrew D. , Thyer Ross
Published: November 2019

While deep learning methods exist to guide protein optimization, examples of novel proteins generated with these techniques require a priori mutational data. Here we report a 3D convolutional neural network that associates amino acids with neighboring chemical microenvironments at state-of-the-art accuracy. This algorithm enables identification of novel gain-of-function mutations, and subsequent experiments confirm substantive phenotypic improvements in stability-associated phenotypes in vivo across three diverse proteins.
Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s Disease
Authors: Leung How-Wing , Foo Gabriel Wei Quan , VanDongen Antonius M.J.
Published: November 2019

The immediate-early gene Arc is a master regulator of synaptic function and a critical determinant of memory consolidation. Arc protein is localized to excitatory synapses, where it controls AMPA receptor endocytosis, and to the nucleus, where it associates with Tip60, a subunit of a chromatin modifying complex. Here we show that Arc interacts with dynamic chromatin loops and associates with histone markers for active enhancers and transcription in cultured hippocampal neurons. When Arc induction by pharmacological network activation was prevented using a short hairpin RNA, the expression profile was altered for over 1900 genes. Many gene families were affected by the absence of Arc, most notably those associated with synaptic function, neuronal plasticity, intrinsic excitability (channels, receptors, transporters), and signaling pathways (transcription factors/regulators). Interestingly, about 100 genes whose activity-dependent expression level depends on Arc are associated with the pathophysiology of Alzheimer’s disease, suggesting a critical role for Arc in the development of neurodegenerative disorders. When endogenous Arc expression was induced in a non-neuronal cell line (HEK293T), the transcription of many neuronal genes was increased, suggesting Arc can control expression in the absence of activated signaling pathways. Taken together, these data establish Arc as a master regulator of neuronal activity-dependent gene expression and a significant factor underlying the pathophysiology Alzheimer’s disease.
Use of a glycan library reveals a new model for enteric virus oligosaccharide binding and virion stabilization
Authors: Lu Hua , Lehrman Mark A. , Pfeiffer Julie K.
Published: November 2019

Enteric viruses infect the gastrointestinal tract and bacteria can promote replication and transmission of several enteric viruses. Viruses can be inactivated by exposure to heat or bleach, but poliovirus, coxsackievirus B3, and reovirus can be stabilized by bacteria or bacterial polysaccharides, limiting inactivation and aiding transmission. We previously demonstrated that certain N-acetylglucosamine (GlcNAc)-containing polysaccharides can stabilize poliovirus. However, the detailed virus-glycan binding specificity and glycan chain length requirements, and thus the mechanism of virion stabilization, has been unclear. A previous limitation was our lack of defined-length glycans to probe mechanisms and consequences of virus-glycan interactions. Here, we generated a panel of polysaccharides and oligosaccharides to determine the properties required for binding and stabilization of poliovirus. Poliovirus virions are non-enveloped icosahedral 30 nm particles with 60 copies of each of four capsid proteins, VP1-4. VP1 surrounds the fivefold axis and our past work indicates that this region likely contains the glycan binding site. We found that relatively short GlcNAc oligosaccharides, such as a six unit GlcNAc oligomer, can bind poliovirus but fail to enhance virion stability. Virion stabilization required binding of long GlcNAc polymers of greater than 20 units. Our data suggest a model where GlcNAc polymers greater than 20 units bind and bridge adjacent fivefold axes, thus aiding capsid rigidity and stability. This study provides a deeper understanding of enteric virus-bacterial glycan interactions, which is important for virion environmental stability and transmission.

Importance

Enteric viruses are transmitted through the fecal-oral route, but how enteric viruses survive in the environment is unclear. Previously, we found that bacterial polysaccharides enhance poliovirus stability against heat or bleach inactivation, but the specific molecular requirements have been unknown. Here we showed that certain short chain oligosaccharides can bind to poliovirus but do not increase virion stability. Long chain polysaccharides bind and may bridge adjacent sites on the viral surface, thus increasing capsid rigidity and stability. This work defines the unique interactions of poliovirus and glycans, which provides insight into virion environmental stability and transmission.
Host fruit as a suitable bacteria growth substrate that promotes larval development of Bactrocera dorsalis (Diptera: Tephritidae)
Authors: Akami Mazarin , Ren Xueming , Wang Yaohui , Mansour Abdelaziz , Cao Shuai , Qi Xuewei , Ngakou Albert , Niu Chang-Ying
Published: November 2019

The ability of a host plant to act as a substrate or media for larval development may depend on how good it is at offering suitable nutrients for bacterial growth. In this study, we hypothesized that the suitability of a fruit type for fruit fly larval development is positively correlated with the ability of that fruit to act as a substrate/media for fruit fly symbiotic bacterial growth. We allowed a single female fruit fly to lay eggs on five different host fruits, then we monitored the larval development parameters across five generations and analyzed the bacterial community structure of larvae developing in 2 of these hosts (apple and banana) at the first and fifth generations. Results indicate that the larval length and dry weight did not vary significantly across experimental generations, but were greatly affected by fruit types and larval stages. The larval development time was extended considerably in apple and tomato but shortened in banana and mango. There was a significant shift in bacterial community structure and composition across fruits and generations. The bacterial community of larvae within the same fruit (apple and banana) clustered and was similar to the parental female (with the predominance of Proteobacteria), but there was a shift at the fifth generation (dominance of Firmicutes). Banana offered a suitable better development and growth to larvae and bacteria, respectively, compared to apple in which reduced larval development and bacterial growth were recorded. Although additional experiments are needed to adequately show that the differences in microbiome seen in fruit fly larval guts are the actual driver of different developmental outcomes of larvae on the different fruits, at the very least, our study has provided intriguing data suggesting interaction between the diets and gut microbial communities on insect development.

Importance and Significance of the study

Tephritid fruit flies entertain complex interactions with gut bacteria. These bacteria are known to provide nutritional benefits to their hosts, by supplementing missing nutrients from the host diets and regulating energy balance. Foraging for food is a risky exercise for the insect which is exposed to ecological adversities, including predators. Therefore, making beneficial choice among available food substrates is a question of survival for the flies and bacteria as well. Our study demonstrates interactions between the host fly and its intestinal bacteria in sustaining the larval development while foraging optimally on different fruit types. These findings add a novel step into our understanding of the interactions between the gut microbial communities and B. dorsalis and provide avenues for developing control strategies to limit the devastative incidence of the fly.
SPOCK1 promotes breast cancer progression via interacting with SIX1 and activating AKT/mTOR signaling pathway
Authors: Xu Ming , Zhang Xianglan , Zhang Songnan , Piao Junjie , Yang Yang , Wang Xinyue , Lin Zhenhua
Published: November 2019

SPOCK1 is highly expressed in many types of cancer, which has been recognized as a promoter of cancer progression, while its regulatory mechanism remains to be clear in breast cancer (BC). This study aimed to explore the precise function of SPOCK1 in BC progression and the mechanism by which SPOCK1 was involved in cell proliferation and epithelial-mesenchymal transition (EMT). Immunohistochemistry (IHC) and database analysis displayed that high expression of SPOCK1 was positively associated with histological grade, lymph node metastasis (LN) and poor clinical prognosis in BC. A series of assays bothin vitroandin vivoelucidated that altering SPOCK1 level led to distinctly changes in BC cell proliferation and metastasis. Investigations of potential mechanisms revealed that SPOCK1 interacted with SIX1 could enhance cell proliferation, cell cycle and EMT process by activating the AKT/mTOR pathway, whereas inhibition of AKT/mTOR pathway or depletion of SIX1 reversed the effects of SPOCK1 overexpression. Furthermore, SPOCK1 and SIX1 were highly expressed in BC and might indicate poor prognoses. Altogether, SPOCK1/SIX1 promoted BC progression by activating AKT/mTOR pathway to accelerate cell proliferation and metastasis in BC, and SPOCK1/SIX1 might be promising clinical therapeutic targets to prevent BC progression.

IMPORTANCE

The incidence of BC is alarmingly high and many patients initially diagnosed without detectable metastases will eventually develop metastatic lesions. The occurrence of metastasis is responsible for the death of many patients, which also represents a big challenge for researchers to improve the survival rates of BC patients. Hence the scientific community pays more attention on cancer targeted therapy. This research is significant for identifying the underlying mechanisms and capabilities of SPOCK1-induced BC activities, which will greatly apply novel targets and new treatment strategies for clinicians, leading to broader biomedical impacts.
Multiplex genomic edition in Ashbya gossypii using CRISPR-Cpf1
Authors: Jiménez Alberto , Hoff Birgit , Revuelta José Luis
Published: November 2019

The CRISPR/Cas technologies constitute an essential tool for rapid genome engineering of many organisms, including fungi. The CRISPR/Cas9 system adapted for the industrial fungus Ashbya gossypii enables the efficient genome editing for the introduction of deletions, insertions and nucleotide substitutions. However, the Cas9 system is constrained to the existence of an specific 5’-NGG-3’ PAM sequence in the target site.

Here we present a new CRISPR/Cas system for A. gossypii that expands the molecular toolbox available for microbial engineering of this fungus. The use of Cpf1 nuclease from Lachnospiraceae bacterium allows to employ a T-rich PAM sequence (5’-TTTN-3’) and facilitates the implementation of a multiplexing CRISPR/Cpf1 system adapted for A. gossypii. The system has been validated for the introduction of large deletions into five different auxotrophic marker genes (HIS3, ADE2, TRP1, LEU2 and URA3). The use of both crRNA and dDNA arrays in a multi-CRISPR/Cpf1 system was demonstrated to be an efficient strategy for multiplex gene deletion of up to four genes using a single multi-CRISPR/Cpf1 plasmid. Our results also suggest that the selection of the target sequence may significantly affect to the edition efficiency of the system.
Allosteric deregulation of phenylalanine biosynthesis evolved with the emergence of vascular plants
Authors: El-Azaz Jorge , Cánovas Francisco M. , Barcelona Belén , Ávila Concepción , de la Torre Fernando
Published: November 2019

Phenylalanine (Phe) is the precursor of essential secondary products in plants. Here we show that a key, rate-limiting step in Phe biosynthesis, which is catalyzed by arogenate dehydratase (ADT), experienced allosteric de-regulation during evolution. Enzymes from microorganisms and type-I ADTs from plants are strongly feedback-inhibited by Phe, while type-II isoforms remain active at high levels of Phe. We have found that type-II ADTs are widespread across seed plants and their overproduction resulted in a dramatic accumulation of Phe in planta, up to 40-times higher than those observed following the expression of type-I enzymes. Punctual changes in the allosteric binding site of Phe and adjacent region are responsible for the observed relaxed regulation. The phylogeny of plant ADTs evidences that the emergence of type-II isoforms with relaxed regulation occurred at some point in the transition between non-vascular plants and tracheophytes enabling the massive production of Phe-derived compounds, primarily lignin, which are attributes of vascular plants.
Neurofibromin regulates metabolic rate via neuronal mechanisms in Drosophila
Authors: Botero Valentina , Stahl Bethany A. , Grenci Eliza C. , Boto Tamara , Park Scarlet J. , King Lanikea B. , Murphy Keith R. , Colodner Kenneth J. , Walker James A. , Keene Alex C. , Ja William W. , Tomchik Seth M.
Published: November 2019

Neurofibromatosis type 1 (NF1) is a genetic disorder predisposing patients to a range of features, the most characteristic of which include areas of abnormal skin pigmentation and benign tumors associated with peripheral nerves, termed neurofibromas. Less common, but more serious symptoms also include malignant peripheral nerve sheath tumors, other malignancies, and learning disabilities. The NF1 gene encodes neurofibromin, a large protein that functions as a negative regulator of Ras signaling and mediates pleiotropic cellular and organismal function. Recent evidence suggests NF1 may regulate metabolism, though the mechanisms are unknown. Here we show that the Drosophila ortholog of NF1, dNf1 regulates metabolic homeostasis in fruit flies by functioning within a discrete brain circuit. Loss of dNf1 increases metabolic rate and feeding, enhances starvation susceptibility, and decreases lipid stores while increasing lipid turnover rate. The increase in metabolic rate is independent of locomotor activity (grooming), and maps to a subset of neurons in the ventral nervous system. The feeding and metabolic rate effects are due to loss of dNf1 in the same set of neurons, suggesting that increased feeding may be a compensatory effect driven by the increase in metabolic rate and lipid turnover. Finally, we show that the Ras GAP-related domain of neurofibromin is required for normal metabolism, demonstrating that Ras signaling downstream of dNf1 mediates the metabolic effects. These data demonstrate that dNf1 regulates metabolic rate via neuronal mechanisms, suggest that cellular and systemic metabolic alterations may represent a pathophysiological mechanism in NF1, and provide a platform for investigating the cellular role of neurofibromin in metabolic homeostasis.
Mechanisms Generating Cancer Genome Complexity From A Single Cell Division Error
Authors: Umbreit Neil T. , Zhang Cheng-Zhong , Lynch Luke D. , Blaine Logan J. , Cheng Anna M. , Tourdot Richard , Sun Lili , Almubarak Hannah F. , Judge Kim , Mitchell Thomas J. , Spektor Alexander , Pellman David
Published: November 2019

The chromosome breakage-fusion-bridge (BFB) cycle is a mutational process that produces gene amplification and genome instability. Signatures of BFB cycles can be observed in cancer genomes with chromothripsis, another catastrophic mutational process. Here, we explain this association by identifying a mutational cascade downstream of chromosome bridge formation that generates increasing amounts of chromothripsis. We uncover a new role for actomyosin forces in bridge breakage and mutagenesis. Chromothripsis then accumulates starting with aberrant interphase replication of bridge DNA, followed by an unexpected burst of mitotic DNA replication, generating extensive DNA damage. Bridge formation also disrupts the centromeric epigenetic mark, leading to micronucleus formation that itself promotes chromothripsis. We show that this mutational cascade generates the continuing evolution and sub-clonal heterogeneity characteristic of many human cancers.
C9orf72-derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility
Authors: Fumagalli Laura , Young Florence L. , Boeynaems Steven , Decker Mathias De , Mehta Arpan R. , Swijsen Ann , Fazal Raheem , Guo Wenting , Moisse Matthieu , Beckers Jimmy , Dedeene Lieselot , Selvaraj Bhuvaneish T. , Vandoorne Tijs , Madan Vanesa , van Blitterswijk Marka , Raitcheva Denitza , McCampbell Alexander , Poesen Koen , Gitler Aaron D. , Koch Phillip , Berghe Pieter Vanden , Thal Dietmar Rudolf , Verfaillie Catherine , Chandran Siddharthan , Van Den Bosch Ludo , Bullock Simon L. , Damme Philip Van
Published: November 2019

Hexanucleotide repeat expansions in the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). How this mutation leads to these neurodegenerative diseases remains unclear. Here, we use human induced pluripotent stem cell-derived motor neurons to show that C9orf72 repeat expansions impair microtubule-based transport of mitochondria, a process critical for maintenance of neuronal function. Cargo transport defects are recapitulated by treating healthy neurons with the arginine-rich dipeptide repeat proteins (DPRs) that are produced by the hexanucleotide repeat expansions. Single-molecule imaging shows that these DPRs perturb motility of purified kinesin-1 and cytoplasmic dynein-1 motors along microtubules in vitro. Additional in vitro and in vivo data indicate that the DPRs impair transport by interacting with both microtubules and the motor complexes. We also show that kinesin-1 is enriched in DPR inclusions in patient brains and that increasing the level of this motor strongly suppresses the toxic effects of arginine-rich DPR expression in a Drosophila model. Collectively, our study implicates an inhibitory interaction of arginine-rich DPRs with the axonal transport machinery in C9orf72-associated ALS/FTD and thereby points to novel potential therapeutic strategies.
Correlated cryogenic fluorescence microscopy and electron cryotomography shows that exogenous TRIM5α can form hexagonal lattices or autophagy aggregates in vivo
Authors: Carter Stephen D , Mamede Joao I , Hope Thomas J. , Jensen Grant J
Published: November 2019

Members of the TRIM protein family have been shown to gather into structures in both the nucleus and cytoplasm. One TRIM protein family member, TRIM5α, has been shown to form cytoplasmic bodies involved in restricting retroviruses such as HIV-1. Here we applied cryogenic correlated light and electron microscopy (cryo-CLEM) to intact mammalian cells expressing YFP-rhTRIM5α and found hexagonal nets were present whose arm-lengths were similar to those of the hexagonal nets formed by purified TRIM5α in-vitro. We also observed YFP-rhTRIM5α within a diversity of structures with characteristics expected for organelles involved in different stages of macroautophagy, including disorganized protein aggregations (sequestosomes), sequestosomes flanked by flat double-membraned vesicles (sequestosome:phagophore complexes), sequestosomes within a double-membraned vesicle (autophagosomes), and sequestosomes within multi-vesicular autophagic vacuoles (autolysosomes or amphisomes). Vaults were also seen in these structures, consistent with their role in autophagy. Our data (i) support recent reports that TRIM5α can form both well-organized signaling complexes and non-signaling aggregates, (ii) offer the first images of the macroautophagy pathway in a near-native state, and (iii) reveal that vaults arrive early in macroautophagy.
Dot1L methyltransferase activity is a barrier to acquisition of pluripotency but not transdifferentiation
Authors: Wille Coral K. , Sridharan Rupa
Published: November 2019

The ability of pluripotent stem cells to be poised to differentiate into any somatic cell type is partly derived from a unique chromatin structure that is depleted for transcriptional elongation associated epigenetic modifications, primarily H3K79 methylation. Inhibiting the H3K79 methyltransferase, Dot1L, increases the efficiency of reprogramming somatic cells to induced pluripotent stem cells (iPSCs) most potently at the mid-point of the process. Surprisingly, despite the enrichment of H3K79me2 on thousands of actively transcribed genes, Dot1L inhibition (Dot1Li) results in few changes in steady state mRNA levels during reprogramming. Dot1Li spuriously upregulates genes not involved in pluripotency and does not shutdown the somatic program. Depletion of the few genes that are downregulated, such as Nfix, enhances reprogramming efficiency in cooperation with Dot1Li. Contrary to the prevalent view, Dot1Li promotes iPSC generation beyond early phases of reprogramming such as the mesenchymal to epithelial transition and from already epithelial cell types including keratinocytes. Significantly, Dot1L inhibition does not enhance lineage conversion to neurons or muscle cells. Taken together, our results indicate that H3K79me is not a universal barrier of cell fate transitions but specifically protects somatic cells from reverting to the pluripotent state.
A trimeric Rab7 GEF controls NPC1-dependent lysosomal cholesterol export
Authors: van den Boomen Dick J.H. , Sienkiewicz Agata , Berlin Ilana , Jongsma Marlieke L.M. , van Elsland Daphne M. , Paul Luzio J. , Neefjes Jacques J.C. , Lehner Paul J.
Published: November 2019

Cholesterol import in mammalian cells is mediated by the LDL receptor pathway. Here, using an endogenous cholesterol reporter in a genome-wide CRISPR screen we identify >70 genes involved in LDL-cholesterol import. We characterise C18orf8 as a core component of the mammalian Mon1-Ccz1 guanidine exchange factor (GEF) for Rab7, required for complex stability and function. C18orf8-deficient cells lack Rab7 activation and show severe defects in late endosome morphology and endosomal LDL trafficking, resulting in cellular cholesterol deficiency. Unexpectedly, free cholesterol accumulates within swollen lysosomes, suggesting a critical additional defect in lysosomal cholesterol export. We find that active Rab7 interacts with the NPC1 cholesterol transporter and licenses lysosomal cholesterol export. This process is abolished in C18orf8-, Ccz1- and Mon1A/B-deficient cells and restored by a constitutively active Rab7. The trimeric Mon1-Ccz1-C18orf8 (MCC) GEF therefore plays a central role in cellular cholesterol homeostasis coordinating Rab7 activation, endosomal LDL trafficking and NPC1-dependent lysosomal cholesterol export.
Small-angle X-ray scattering intensity of multiscale models of spheres
Authors: Sorbier Loïc , Moreaud Maxime , Humbert Séverine
Published: November 2019

The different approaches found in the literature to compute small-angle X-ray scattering intensities of stochastic Boolean models from their analytical formulations or their numerical realizations are reviewed. The advantages and drawbacks of the methods for the interpretation of small-angle X-ray scattering curves are investigated. Examples of multiscale models built from union and intersection of Boolean models of spheres and from Gamma or lognormal radius distributions are given. The scattering intensity computed from projections of realizations of such models is compared with the intensity computed from their analytical covariance. It appears that computation from projection induces a strong finite-size effect with a relative constant variance equal to 0.5. Comparison of scattering intensities of an intersection of Boolean model and the corresponding Cox model shows only subtle differences.
Hardening tungsten carbide by alloying elements with high work function
Authors: Lu Hao , Zhao Chong , Wang Haibin , Liu Xuemei , Yu Rong , Song Xiaoyan
Published: November 2019

There is intensive searching for superhard materials in both theoretical and experimental studies. Refractory and transition metal carbides are typical materials with high hardness. In this study, first-principles calculations were performed first to analyze the electronic structures and mechanical properties of the tungsten-carbide-based compounds. The results indicated that tungsten carbide could be hardened by alloying elements with high work functions to tailor the Fermi level and electron density. Guided by the calculations, a new type of tungsten carbide alloyed with Re was synthesized. The Young's modulus and hardness of the Re-alloyed tungsten carbide are increased by 31% and 44%, respectively, as compared with those of tungsten carbide. This study provides a new methodology to design superhard materials on a feasible electronic base using work function as a simple guiding parameter.
The first- and second-order isothermal phase transitions in Fe3Ga-type compounds
Authors: Balagurov Anatoly M. , Samoylova Nataliya Yu. , Bobrikov Ivan A. , Sumnikov Sergey V. , Golovin Igor S.
Published: November 2019

Structural features and kinetics of the transition between ordered metastable b.c.c.-derived D03 and equilibrium f.c.c.-derived L12 phases of Fe–xGa alloys (x = 27.2% and 28.0%) have been analyzed by in situ real-time neutron diffraction during isothermal annealing in the temperature range 405–470°C. It has been revealed that the transition proceeds with alternation of the first- and second-order phase transformations according to a D03 → A2 → A1 → L12 scheme, where A2 and A1 are disordered b.c.c. and f.c.c. structures. Deformations of the crystal lattice that arise due to these transitions are determined. The kinetics of the L12 phase nucleation and growth were analyzed in the frame of the Johnson–Mehl–Avrami–Kolmogorov (JMAK) model; however, only the early stage of the D03 → L12 transition is well described by the JMAK equation. The value of the Avrami exponent corresponds to the constant growth rate of the new L12 phase and decreasing nucleation rate in the Fe–27.2Ga alloy and indicates the presence of pre-existing nucleation centres of the L12 phase in the Fe–28.0Ga alloy.
Factors associated with the severity of IPV perpetrated by substance using men towards current partner
Authors: Canfield Martha , Radcliffe Polly , D’Oliveira Ana Flavia Pires Lucas , Gilchrist Gail
Published: November 2019

Purpose

The purpose of this paper is to examine frequency and correlates of intimate partner violence (IPV) severity perpetrated by heterosexual men receiving treatment for substance use towards a current partner in the past 12 months.

Design/methodology/approach

A secondary analysis of a self-reported questionnaire (n=162) completed by men receiving treatment for substance use in England and Brazil was conducted. Types of IPV perpetration (emotional, physical and/or sexual IPV) and frequency of occurrence were assessed. A five level ordinal variable for IPV perpetration severity was created: no IPV, minor; moderate, low severe and high severe. Psychological and cultural correlates of perpetration severity were explored using ordinal logistic regression.

Findings

Approximately four in ten men reported perpetrating IPV towards their partner in the past 12 months, one in ten reported perpetrating severe IPV (including hitting with something, kicking or beating, choking or burning, threatening with/using a weapon, sexual IPV and frequent emotional IPV) during this period. A number of correlates of perpetration severity were identified: experiencing childhood physical abuse, witnessing IPV in childhood, perpetrating IPV in previous relationships, committing violence towards another man, controlling behaviours, technology-facilitated abuse, depressive symptoms, having a substance using partner, receiving treatment for illicit drug use, hazardous drinking and poly-drug use.

Research limitations/implications

Despite the small sample size, small to large positive associations were observed between reporting IPV perpetration and several factors. These factors could be targeted to improve identification and assessment of IPV among men receiving treatment for substance use.

Originality/value

A strength of this study methodology is the use of a specific 12 months time frame for the perpetration of IPV towards current partner. The categorisation of levels of IPV perpetration based on types and frequency of violence occurrence was an additional valuable contribution of this study.
Making investment decisions using XBRL filing data
Authors: Palas Rimona , Baranes Amos
Published: November 2019

Purpose

The Securities Exchange Commission mandated eXtensible Business Reporting Language (XBRL) filing data provide immediate availability and easy accessibility for both academics and practitioners. To be useful, this data should provide information for decisions, specifically, investment decisions. The purpose of this study is to examine whether the XBRL database can be used with models, developed in previous studies, predicting the directional movement of earnings. The study does not attempt to examine the validity of these models, but only the ability to use the data in the analysis of financial statements based on these models.

Design/methodology/approach

The study analyzes New York Stock Exchange companies’ XBRL data using a two-step logistic regression model. The model is then used to arrive at the directional movement of earnings between current and subsequent quarters. Additional models are created by dividing the sample into industry membership.

Findings

The results classified companies as realizing an increase or a decrease in earnings. The final model indicated a significant ability to predict earnings changes, on average about 65 per cent of the time, for the entire model, and 71 per cent, for the industry-based models (higher than those of previous studies based on COMPUSTAT). The investment strategy created average quarterly return between 2.8 and 10.7 per cent.

Originality/value

The originality of this study is in the way it examines the quality of XBRL data, by examining whether findings from prior research which relied on traditional databases (such as COMPUSTAT) still hold using XBRL data. The use of XBRL allows not only easier and less-costly access to the data but also the ability to adjust the models almost immediately as current information is posted, thus providing a much more relevant tool for investors, especially small investors.
Monitoring climate change related biodeterioration of protected historic buildings
Authors: Austigard Mari Sand , Mattsson Johan
Published: November 2019

Purpose

Expected rates of biodeterioration in heritage buildings under historic conditions are well known. Deteriorating organisms will benefit from a warmer and wetter climate, giving faster and less predictable rates of deterioration. The Directorate for Cultural Heritage in Norway has requested development of a programme for long-term monitoring of climate change impacts to historic buildings. The development process and resulting monitoring system are previously described. The paper aims to discuss this issue.

Design/methodology/approach

An initial conditions survey is performed, and reference points are chosen in each building. Two microclimatic biodeterioration monitoring panels (MBM panels) are mounted in every building. The MBM panels monitor temperature, relative humidity and wood moisture content, and have standard wooden blocks for investigation of mould growth. The panels will show both the influence of outdoor climate on microclimate inside the building, and the connection between microclimate and activity of degrading organisms.

Findings

High competence and multi-disciplinary approach from the personnel involved are essential to balance flexibility and rigidity and decide the damages that are probably influenced by climate change. Extensive knowledge and experience in surveys of biodeterioration damages in heritage buildings is necessary to distinguish “normal” biodeterioration from biodeterioration caused by climate changes. The MBM panels are essential for possible establishment of causality between damages and climate change.

Originality/value

The authors believe that the methods described give the best possible grounds for future evaluation of damages and microclimatic conditions in buildings compared to changes in regional climatic conditions. Establishment of causality between climate change and development in biological deterioration is still a challenging task.
University entrepreneurial push strategy and students’ entrepreneurial intention
Authors: Wegner Douglas , Thomas Elisa , Teixeira Eduardo Künzel , Maehler Alisson Eduardo
Published: November 2019

Purpose

The purpose of this paper is to question whether the university entrepreneurial push strategy influences the entrepreneurial intention (EI) of its students. Previous research followed multilevel approaches that jointly addressed the impact of individual characteristics, institutional environment, and educational support on EI. Despite these efforts, the extant literature did not consider differences between universities regarding the whole set of activities they perform to foster entrepreneurship among students and their results.

Design/methodology/approach

Through partial least squares structural equation modeling (PLS-SEM) procedures, this study compared data from 447 students of two Brazilian universities that differentiate themselves according to entrepreneurial push strategies (one adopts actions consistent with this type of strategy while the other does not). Whilst University 1 fosters entrepreneurship by investing in entrepreneurship courses, promoting entrepreneurship competitions, and offering incubation opportunities, University 2 primarily focuses on traditional managerial education without a specific focus on entrepreneurial activities.

Findings

Surprisingly, the results have shown the entrepreneurial push strategy of University 1 does not account for differences in the students’ EI when compared to University 2. Such finding contradicts previous studies on the effects of entrepreneurial education and sheds new lights on the role university’s support plays to foster entrepreneurship intention.

Research limitations/implications

Contributions to the literature on the field of entrepreneurship intention were made by showing that the efforts toward the promotion of entrepreneurship through entrepreneurship education, business plan competitions, and incubation might not have a direct influence on students’ EI.

Practical implications

As a practical implication, the study stimulates universities to evaluate the effectiveness of their efforts in promoting entrepreneurship through training, education and support for new ventures. The results also offer policy implications by suggesting that public policies should emphasize the development of institutions that foster a positive business environment, facilitate the creation of new ventures, the funding of start-ups and reinforce the benefits of becoming an entrepreneur.

Originality/value

The results are surprising because they contradict previous studies of the university’s role in fostering entrepreneurship intention. To the best of our knowledge, it is the first research comparing universities with two different approaches toward developing students’ EI: one university with a whole set of activities and another university without any specific activity with that purpose.
Evaluation of offending behaviour programme selection: the PNA
Authors: Ramsay Laura , Walton Jamie S. , Frost Gavin , Rewaj Chloe , Westley Gemma , Tucker Helen , Millington Sarah , Dhar Aparna , Martin Gemma , Gill Caitriona
Published: November 2019

Purpose

The purpose of this paper is to outline the qualitative research findings of the effectiveness of Her Majesty’s Prison and Probation Service Programme Needs Assessment (PNA) in supporting decision making regarding selection onto high-intensity offending behaviour programmes.

Design/methodology/approach

Qualitative data analysis was used through the application of thematic analysis. Results were pooled using principles from meta-synthesis in order to draw conclusions as to whether the PNA was operating as designed.

Findings

Four overarching themes were identified, which have meaning in guiding decision making into, or out of high-intensity programmes. These were risk, need and responsivity, the importance of attitudes, motivation and formulation and planning.

Research limitations/implications

The majority of data were collected from category C prisons. Generalisability of findings to high-intensity programmes delivered in maximum security prisons and prisons for younger people aged 18–21 years is limited. The research team had prior knowledge of the PNA, whether through design or application. Procedures were put in place to minimise researcher biases.

Practical implications

Findings suggest that the PNA is effective in guiding clinical decision making. Practitioners and policy makers can be assured that the processes in place to select into high-intensity programmes are effective, and aligned with the What Works in reducing re-offending.

Originality/value

This is the first evaluation into the effectiveness of the PNA designed to support clinical decision making regarding participant selection onto accredited offending behaviour programmes. Implications for practice have been discussed.
Presence of financial information in local politicians’ speech
Authors: Sinervo Lotta-Maria , Haapala Petra
Published: November 2019

Purpose

The highest decision-making body in a municipality is the council, whose members are elected every fourth year. Therefore, local politicians are in the key position in using financial information in decision making. The purpose of this paper is to study Finnish local politicians’ use of financial information.

Design/methodology/approach

This paper studies the speech of local politicians as they describe financial operations and financial position of the municipalities they represent. Here, the words of local politicians are considered an expression of their use of financial information. The use of financial information includes its impact on decision making. The focus is on the impact of different individual characteristics of financial information use in speech about financial operations and financial position. The paper employs qualitative empirical data collected through semi-structured thematic interviews with members of the Finnish local government. Data are analyzed with descriptive statistical methods.

Findings

Local politicians use financial information when they talk about financial operations and financial position of their municipality. Individual characteristics, such as political experience, affect the use of financial information. Experienced local politicians are familiar with financial information and use it more systematically than inexperienced politicians. Contrasted to expectations, financial expertise has a negative impact on financial information use. Moreover, in general, the ideology of politicians does not affect their use of financial information.

Originality/value

The paper sheds light on the value of individual characteristics of financial information use. It develops and tests hypotheses based on previous research on the impact of individual attributes of local politicians in the Finnish local government.
The emergence of connected discretion
Authors: Rolandsson Bertil
Published: November 2019

Purpose

Previous studies repeatedly claim that social media challenge and even disrupt organizational boundaries conditioning discretionary work. The purpose of this paper is to investigate how police officers, drawing on institutionalized value logics, actively shape their awareness of how to use social media with discretion.

Design/methodology/approach

Drawing on semi-structured interviews with police officers from Sweden, the analysis explores similarities and variations in how they assess their discretionary awareness of how to manage social media potentials across different police practices. Supporting documents have been analyzed to put interviews into context.

Findings

The analysis shows how police officers justify their awareness of how to manage two social media potentials providing communicative efficiency and networking opportunities, by applying two justificatory modalities of momentary reconciliation. Contributing to previous research, findings show how these modalities accommodate tensions between different value logics urging officers to engage in situated problem solving or moderation of the intensity in different connections. By drawing on discretionary awareness about enduring value tensions, police officers maintain legitimate claims on social media discretion. The study also complements previous research depicting digital communication and discretion as mutually exclusive. Findings suggest that web-based digitalization like social media raises new demands of awareness of a connected discretion.

Originality/value

Previous research rarely analyses officers’ awareness of how to manage idiosyncratic social media challenges. By introducing the concept discretionary awareness, this study illuminates how arrangements of institutionalized value logics guide police officers in applying “good judgment” in day-to-day use of social media.
Evaluation of treatment effect estimates in single‐case experimental research: comparison of twelve overlap methods and visual analysis
Authors: Yucesoy‐Ozkan Serife , Rakap Salih , Gulboy Emrah
Published: November 2019

The purpose of this study was to compare 12 commonly‐used nonoverlap methods with each other and with the results of visual analysis. Data were obtained from 25 studies focused on embedded instruction and schema‐based instruction and included a total of 101 graphs. Treatment effect estimates using 12 nonoverlap methods were calculated for each graph by hand or using an online calculator. Five experts conducted visual analysis of each graph. Results showed that strong agreements existed between visual analysis and PND, TauNOVLAP and Tau‐U when raw data were analysed, and PND, PNCD and PEM‐T when categorised data were analysed. Of the 12 methods investigated, PND had the highest agreement rate with visual analysis, followed by PEM‐T, PAND, PNCD, IRD, NAP and TauNOVLAP. Overall, visual analysis appeared to be more conservative, as most nonoverlap methods overestimated the treatment effect. Additional research is needed to replicate and potentially validate the findings of this study.