bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient approaches for large scale GWAS studies with genotype uncertainty
Authors: Jørsboe Emil , Albrechtsen Anders
Published: October 2019

1

Introduction

Association studies using genetic data from SNP-chip based imputation or low depth sequencing data provide a cost efficient design for large scale studies. However, these approaches provide genetic data with uncertainty of the observed genotypes. Here we explore association methods that can be applied to data where the genotype is not directly observed. We investigate how using different priors when estimating genotype probabilities affects the association results in different scenarios such as studies with population structure and varying depth sequencing data. We also suggest a method (ANGSD-asso) that is computational feasible for analysing large scale low depth sequencing data sets, such as can be generated by the non-invasive prenatal testing (NIPT) with low-pass sequencing.

Methods

ANGSD-asso’s EM model works by modelling the unobserved genotype as a latent variable in a generalised linear model framework. The software is implemented in C/C++ and can be run multi-threaded enabling the analysis of big data sets. ANGSD-asso is based on genotype probabilities, they can be estimated in various ways, such as using the sample allele frequency as a prior, using the individual allele frequencies as a prior or using haplotype frequencies from haplotype imputation. Using simulations of sequencing data we explore how genotype probability based method compares to using genetic dosages in large association studies with genotype uncertainty.

Results & Discussion

Our simulations show that in a structured population using the individual allele frequency prior has better power than the sample allele frequency. If there is a correlation between genotype uncertainty and phenotype, then the individual allele frequency prior also helps control the false positive rate. In the absence of population structure the sample allele frequency prior and the individual allele frequency prior perform similarly. In scenarios with sequencing depth and phenotype correlation ANGSD-asso’s EM model has better statistical power and less bias compared to using dosages. Lastly when adding additional covariates to the linear model ANGSD-asso’s EM model has more statistical power and provides less biased effect sizes than other methods that accommodate genotype uncertainly, while also being much faster. This makes it possible to properly account for genotype uncertainty in large scale association studies.
Decoding age-related changes in the spatiotemporal neural processing of speech using machine learning
Authors: Mahmud Md Sultan , Ahmed Faruk , Al-Fahad Rakib , Moinuddin Kazi Ashraf , Yeasin Mohammed , Alain Claude , Bidelman Gavin M.
Published: October 2019

Speech comprehension in noisy environments depends on complex interactions between sensory and cognitive systems. In older adults, such interactions may be affected, especially in those individuals who have more severe age-related hearing loss. Using a data-driven approach, we assessed the temporal (when in time) and spatial (where in the brain) characteristics of the cortex’s speech-evoked response that distinguish older adults with or without mild hearing loss. We used source montage to model scalp-recorded during a phoneme discrimination task conducted under clear and noise-degraded conditions. We applied machine learning analyses (stability selection and control) to choose features of the speech-evoked response that are consistent over a range of model parameters and support vector machine (SVM) classification to investigate the time course and brain regions that segregate groups and speech clarity. Whole-brain data analysis revealed a classification accuracy of 82.03% [area under the curve (AUC)=81.18%; F1-score 82.00%], distinguishing groups within ∼50 ms after speech onset (i.e., as early as the P1 wave).We observed lower accuracy of 78.39% [AUC=78.74%; F1-score=79.00%] and delayed classification performance when the speech token were embedded in noise, with group segregation at 60 ms. Separate analysis using left (LH) and right hemisphere (RH) regions showed that LH speech activity was better at distinguishing hearing groups than activity measured over the RH. Moreover, stability selection analysis identified 13 brain regions (among 1428 total spatiotemporal features from 68 regions) where source activity segregated groups with >80% accuracy (clear speech); whereas 15 regions were critical for noise-degraded speech to achieve a comparable level of group segregation (76% accuracy). Our results identify two core neural networks associated with complex speech perception in older adults and confirm a larger number of neural regions, particularly in RH and frontal lobe, are active when processing degraded speech information.
Functional Maturation of Human iPSC-based Cardiac Microphysiological Systems with Tunable Electroconductive Decellularized Extracellular Matrices
Authors: Tsui Jonathan H. , Leonard Andrea , Camp Nathan D. , Long Joseph T. , Nawas Zeid Y. , Chavanachat Rakchanok , Choi Jong Seob , Wolf-Yadlin Alejandro , Murry Charles E. , Sniadecki Nathan J. , Kim Deok-Ho
Published: October 2019

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer tremendous potential for use in engineering human tissues for regenerative therapy and drug screening. However, differentiated cardiomyocytes are phenotypically immature, reducing assay reliability when translatingin vitroresults to clinical studies and precluding hiPSC-derived cardiac tissues from therapeutic usein vivo. To address this, we have developed hybrid hydrogels comprised of decellularized porcine myocardial extracellular matrix (dECM) and reduced graphene oxide (rGO) to provide a more instructive microenvironment for proper cellular and tissue development. A tissue-specific protein profile was preserved post-decellularization, and through the modulation of rGO content and degree of reduction, the mechanical and electrical properties of the hydrogels could be tuned. Engineered heart tissues (EHTs) generated using dECM-rGO hydrogel scaffolds and hiPSC-derived cardiomyocytes exhibited significantly increased twitch forces at 14 days of culture and had increased the expression of genes that regulate contractile function. Similar improvements in various aspects of electrophysiological function, such as calcium-handling, action potential duration, and conduction velocity, were also induced by the hybrid biomaterial. We also demonstrate that dECM-rGO hydrogels can be used as a bioink to print cardiac tissues in a high-throughput manner, and these tissues were utilized to assess the proarrhythmic potential of cisapride. Action potential prolongation and beat interval irregularities was observed in dECM-rGO tissues at clinical doses of cisapride, indicating that the enhanced maturation of these tissues corresponded well with a capability to produce physiologically relevant drug responses.
Surviving in high stress environments: Physiological and molecular responses of lobe coral indicate nearshore adaptations to anthropogenic stressors
Authors: Tisthammer Kaho H , Timmins-Schiffman Emma , Seneca Francois O , Nunn Brook L , Richmond Robert H
Published: October 2019

Corals in nearshore marine environments are increasingly exposed to reduced water quality, which is the primary local threat to Hawaiian coral reefs. It is unclear if corals surviving in such conditions have adapted to withstand sedimentation, pollutants, and other environmental stressors. Lobe coral populations from Maunalua Bay, Hawaii showed clear genetic differentiation between the ’polluted, high-stress’ nearshore site and the ’lower-stress’ offshore site. To understand the driving force of the observed genetic partitioning, reciprocal transplant and common-garden experiments were conducted to assess phenotypic differences between these two populations. Physiological responses were significantly different between the populations, revealing more stress-resilient traits in the nearshore corals. Changes in protein profiles between the two populations highlighted the inherent differences in the cellular metabolic processes and activities; nearshore corals did not significantly alter their proteome between the sites, while offshore corals responded to nearshore transplantation with increased abundances of proteins associated with detoxification, antioxidant defense, and regulation of cellular metabolic processes. The response differences across multiple phenotypes between the populations suggest local adaptation of nearshore corals to reduced water quality. Our results provide insight into coral’s adaptive potential and its underlying processes, and reveal potential protein biomarkers that could be used to predict resiliency.
Overnight caloric restriction prior to cardiac arrest and resuscitation leads to improved survival and neurological outcome in a rodent model
Authors: Azadian Matine , Tian Guilian , Bazrafkan Afsheen , Maki Niki , Rafi Masih , Desai Monica , Otarola Ieeshiah , Zaher Shuhab , Khan Ashar , Suri Yusuf , Wang Minwei , Steward Oswald , Akbari Yama
Published: October 2019

While interest toward caloric restriction (CR) in various models of brain injury has increased in recent decades, studies have predominantly focused on the benefits of chronic or intermittent CR. The effects of ultra-short, including overnight, CR on acute ischemic brain injury, however, are not well studied. Here, we show that overnight caloric restriction (75% over 14 h) prior to asphyxial cardiac arrest and resuscitation (CA) improves survival and neurological recovery, including complete prevention of neurodegeneration in multiple regions of the brain. We also show that overnight CR normalizes stress-induced hyperglycemia, while significantly decreasing insulin and glucagon production and increasing corticosterone and ketone body production. The benefits seen with ultra-short CR appear independent of Sirtuin 1 (SIRT-1) and brain-derived neurotrophic factor (BDNF) expression, which have been strongly linked to neuroprotective benefits seen in chronic CR. Further exploration into the precise mechanisms involved in ultra-short CR may have significant translational implications. These findings are also of importance to basic sciences research as we demonstrate that minor, often-overlooked alterations to pre-experimental dietary procedures can significantly affect results, and by extension, research homogeneity and reproducibility, especially in acute ischemic brain injury models.
The genome of Mekong tiger perch (Datnioides undecimradiatus) provides insights into the phylogenic position of Lobotiformes and biological conservation
Authors: Sun Shuai , Wang Yue , Du Xiao , Li Lei , Hong Xiaoning , Huang Xiaoyun , Zhang He , Zhang Mengqi , Fan Guangyi , Liu Xin , Liu Shanshan
Published: October 2019

Mekong tiger perch (Datnioides undecimradiatus) is one ornamental fish and a vulnerable species, which belongs to order Lobotiformes. Here, we report a ∼595 Mb D. undecimradiatus genome, which is the first whole genome sequence in the order Lobotiformes. Based on this genome, the phylogenetic tree analysis suggested that Lobotiformes and Sciaenidae are closer than Tetraodontiformes, resolving a long-time dispute. We depicted the pigment synthesis pathway in Mekong tiger perch and result confirmed that this pathway had evolved from the shared whole genome duplication. We also estimated the demographic history of Mekong tiger perch, showing the effective population size suffered a continuous reduction possibly related to the contraction of immune-related genes. Our study provided a reference genome resource for the Lobotiformes, as well as insights into the phylogeny of Eupercaria and biological conservation.
Detection of AmpC β-lactamases in Escherichia coli using different screening agars
Authors: den Drijver Evert , Verweij Jaco J. , Verhulst Carlo , Soer Joke , Veldman Kees , Rossen John W. , Kooistra-Smid A.M.D. (Mirjam) , Kluytmans van den Bergh Marjolein F. Q. , Kluytmans Jan A. J. W.
Published: October 2019

The aim of this study was to determine the performance of both cefotaxime and ceftazidime containing agars on the specificity and sensitivity for chromosomal AmpC-hyperproducing and plasmid AmpC harboring Escherichia coli compared to ESBL-producing E. coli and E. coli without ESBL, pAmpC or cAmpC hyperproduction. Second, we evaluated the influence of adding cefoxitin to these agars for detection of both chromosomal AmpC-hyperproducing and plasmid AmpC harboring E. coli.

Four different homemade screening agars with cefotaxime (1mg/L), ceftazidime (1mg/L), cefotaxime (1mg/L) with cefoxitin (8mg/L), and ceftazidime (1mg/L) with cefoxitin (8mg/L) were compared to each other for the identification of AmpC producing E. coli. A total of 40 isolates with plasmid encoded AmpC β-lactamases, 40 isolates with alterations in the promoter/attenuator region of the AmpC gene leading to hyperproduction of the β-lactamase, 40 isolates with ESBL genes and 39 isolates lacking both a AmpC and ESBL genotype were used to test the four agars.

The sensitivity and specificity were 100% (95% confidence interval (95% CI) 96.1% to 100%) and 48.1% (95% CI 38.6%-60.2%), respectively, for the cefotaxime agar; 100% (95% CI 96.1% to 100%) and 49.41% (95% CI 39.8%-61.4%), respectively, for the ceftazidime agar; 96.3% (95% CI 89.1% to 99.2%) and 77.2% (95% CI 66.7%-85.2%) respectively, for the cefotaxime with cefoxitin agar; 98.8% (95% CI) 92.6% to 99.6%) and 81.0% (95% CI 70.9%-88.3%) respectively, for the ceftazidime agar with cefoxitin. The main reason for false-positive results were ESBL-harboring strains that grew on various agars; therefore, the specificity of each agar reported here was influenced mainly by the proportion of ESBL isolates tested. In conclusion addition of cefoxitin to cefotaxime and ceftazidime containing agars had little influence on sensitivity, but increased specificity for the detection of AmpC in E. coli.
Electrospun cellulose acetate/gelatin nanofibrous wound dressing containing berberine for diabetic foot ulcer healing: in vitro and in vivo studies
Authors: Samadian Hadi , Ehterami Arian , Farzamfar Saeed , Vaez Ahmad , Khastar Hossein , Alam Mostafa , Ai Armin , Allahyari Zahra , Salehi Majid
Published: October 2019

Functional dressing with tailored physicochemical and biological properties is vital for diabetic foot ulcer (DFU) treatment. Our main objective in the current study was to fabricate Cellulose Acetate/Gelatin (CA/Gel) electrospun nanofibrous mat loaded with berberine (Beri) as the DFU dressing. The results demonstrated that the diameter of the nanofibers was around 502 nm, the tensile strength, contact angle, porosity, water vapor permeability, and water uptake ratio of CA/Gel nanofibers were around 2.83 MPa, 58.07, 78.17 %, 11.23 mg/cm2 hr, and 12.78 respectively, while these values for CA/Gel/Beri nanofibers were 2.69 ± 0.05 MPa, 56.93 ± 1, 76.17 ± 0.76 %, 10.17 ± 0.21 mg/cm2 hr, 14.37 ± 0.42 respectively. The bacterial evaluations demonstrated that the dressings are an excellent barrier against bacterial penetration with potent antibacterial activity. The animal studies depicted that the collagen density and angiogenesis score in the CA/Gel/Beri treated group were 88.8±6.7 % and 19.8±3.8, respectively. These findings implied that the incorporation of berberine did not compromise the physical properties of dressing, while improving the biological activates. In conclusion, our findings implied that the prepared mat is a proper wound dressing for DFU management and treatment.
PseudomonasmRNA 2.0: Boosting Gene Expression Through Enhanced mRNA Stability and Translational Efficiency
Authors: Neves Dário , Vos Stefan , Blank Lars M. , Ebert Birgitta E.
Published: October 2019

High gene expression of enzymes partaking in recombinant production pathways is a desirable trait among cell factories belonging to all different kingdoms of life. High enzyme abundance is generally aimed for by utilizing strong promoters, which ramp up gene transcription and mRNA levels. Increased protein abundance can alternatively be achieved by optimizing the expression on the post-transcriptional level. Here, we evaluated protein synthesis with a previously proposed optimized gene expression architecture, in which mRNA stability and translation initiation are modulated by genetic parts such as self-cleaving ribozymes and a bicistronic design, which have initially been described to support the standardization of gene expression. The optimized gene expression architecture was tested inPseudomonas taiwanensisVLB120, a promising, novel microbial cell factory. The expression cassette was employed on a plasmid basis and after single genomic integration. We used three constitutive and two inducible promoters to drive the expression of two fluorescent reporter proteins and a short acetoin biosynthesis pathway. The performance was confronted with that of a traditional expression cassette harboring the same promoter and gene of interest but lacking the genetic parts for increased expression efficiency. The optimized expression cassette granted higher protein abundance independently of the expression basis or promoter used proving its value for applications requiring high protein abundance.
Tissue-autonomous immune response regulates stress signalling during hypertrophy
Authors: Krautz Robert , Khalili Dilan , Theopold Ulrich
Published: October 2019

Postmitotic tissues are incapable of replacing damaged cells through proliferation, but need to rely on buffering mechanisms to prevent tissue disintegration. By constitutively activating the Ras/MAPK-pathway viaRasV12-overexpression in the postmitotic salivary glands ofDrosophilalarvae, we overrode the glands adaptability to growth signals, induced hypertrophy and stress accumulation. This allowed us to decipher a novel, spatio-temporally regulated interaction between the JNK-stress response and a genuine tissue-autonomous immune response. Central to this interaction is the direct inhibition of JNK-signalling by the antimicrobial peptide Drosomycin, which blocks programmed cell death and prevents recognition of the stressed tissue by the systemic immune response. While this mechanism might allow growing salivary glands to cope with temporary stress, continuous expression of Drosomycin favors survival of unrestricted, hypertrophicRasV12-glands. Our findings indicate the necessity for refined therapeutic approaches that fundamentally acknowledge detrimental effects that stimulated immune responses have on tissues coping with damage and stress.
The involvement of neuroimmune cells in adipose innervation
Authors: Blaszkiewicz Magdalena , Wood Elizabeth , Koizar Sigi , Willows Jake , Anderson Ryan , Tseng Yu-Hua , Godwin James , Townsend Kristy L.
Published: October 2019

Background

Innervation of adipose tissue is essential for the proper function of this critical metabolic organ. Numerous surgical and chemical denervation studies have demonstrated how maintenance of brain-adipose communication through both sympathetic efferent and sensory afferent nerves helps regulate adipocyte size, cell number, lipolysis, and ‘browning’ of white adipose tissue. Neurotrophic factors are growth factors that promote neuron survival, regeneration and plasticity, including neurite outgrowth and synapse formation. Peripheral blood immune cells have been shown to be a source of neurotrophic factors in humans and mice. Although a number of immune cells reside in the adipose stromal vascular fraction (SVF), it has remained unclear what roles they play in adipose innervation. We previously demonstrated that adipose immune cells secrete brain derived neurotrophic factor (BDNF).

Methods

We now show that deletion of this neurotrophic factor from the myeloid lineage led to a ‘genetic denervation’ of inguinal subcutaneous white adipose tissue (scWAT), thereby causing decreased energy expenditure, increased adipose mass, and a blunted UCP1 response to cold stimulation.

Results

We and others have previously shown that noradrenergic stimulation via cold exposure increases adipose innervation in the inguinal depot. Here we have identified a subset of myeloid cells that home to scWAT upon cold exposure and are Ly6C + CCR2 + Cx3CR1 + monocytes/macrophages that express noradrenergic receptors and BDNF.

Conclusions

We propose that these cold induced neuroimmune cells (CINCs) are key players in maintaining adipose innervation as well as promoting adipose nerve remodeling under noradrenergic stimulation, such as cold exposure.
A Normative Bayesian Model of Classification for Agents with Bounded Memory
Authors: Lee Heeseung , Lee Hyang-Jung , Choe Kyoung Whan , Lee Sang-Hun
Published: October 2019

Classification, one of the key ingredients for human cognition, entails establishing a criterion that splits a given feature space into mutually exclusive subspaces. In classification tasks performed in daily life, however, a criterion is often not provided explicitly but instead needs to be guessed from past samples of a feature space. For example, we judge today’s temperature to be “cold” or “warm” by implicitly comparing it against a “typical” seasonal temperature. In such situations, establishing an optimal criterion is challenging for cognitive agents with bounded memory because it requires retrieving an entire set of past episodes with precision. As a computational account for how humans carry out this challenging operation, we developed a normative Bayesian model of classification (NBMC), in which Bayesian agents, whose working-memory precision decays as episodes elapse, continuously update their criterion as they perform a binary perceptual classification task on sequentially presented stimuli. We drew a set of specific implications regarding key properties of classification from the NBMC, and demonstrated the correspondence between the NBMC and human observers in classification behavior for each of those implications. Furthermore, in the functional magnetic resonance imaging responses acquired concurrently with behavioral data, we identified an ensemble of brain activities that coherently represent the latent variables, including the inferred criterion, of the NBMC. Given these results, we believe that the NBMC is worth being considered as a useful computational model that guides behavioral and neural studies on perceptual classification, especially for agents with bounded memory representation of past sensory events.

Significant Statement

Although classification—assigning events into mutually exclusive classes—requires a criterion, people often have to perform various classification tasks without explicit criteria. In such situations, forming a criterion based on past experience is quite challenging because people’s memory of past events deteriorates quickly over time. Here, we provided a computational model for how a memory-bounded yet normative agent infers the criterion from past episodes to maximally perform a binary perceptual classification task. This model successfully captured several key properties of human classification behavior, and the neural signals representing its latent variables were identified in the classifying human brains. By offering a rational account for memory-bonded agents’ classification, our model can guide future behavioral and neural studies on perceptual classification.
Stable behavioral and neural responses to thermal stimulation despite large changes in theHydra vulgarisnervous system
Authors: Tzouanas Constantine N. , Kim Soonyoung , Badhiwala Krishna N. , Avants Benjamin W. , Robinson Jacob T.
Published: October 2019

Many animals that lose neural tissue due to injury or disease have the ability to maintain their behavioral abilities by regenerating new neurons or reorganizing existing neural circuits. However, most small model organisms used for neuroscience like nematodes and flies lack this high degree of neural plasticity. These animals often show significant behavioral deficits if they lose even a single neuron. Here we show that the small freshwater cnidarianHydra vulgariscan maintain stable sensory motor behaviors even after losing half of the neurons in its body. Specifically, we find that both the behavioral and neural response to a rapid change in temperature is maintained if we make their nervous system roughly 50% smaller by caloric restriction or surgery. These observations suggest thatHydraprovides a rich model for studying how animals maintain stable sensory-motor responses within dynamic neural circuit architectures, and may lead to general principles for neural circuit plasticity and stability.

Significance Statement

The ability of the nervous system to restore its function following injury is key to survival for many animals. Understanding this neural plasticity in animals across the phylogenetic tree would help reveal fundamental principles of this important ability. To our knowledge, the discovery of a set of neurons in the jellyfish polypHydra vulgaristhat stably support a response to thermal stimulation is the first demonstration of large-scale neural plasticity in a genetically tractable invertebrate model organism. The small size and transparency ofHydrasuggests that it will be possible to study large-scale neural circuit plasticity in an animal where one can simultaneously image the activity of every neuron.
Hey, look over there: Distraction effects on rapid sequence recall
Authors: Miner Daniel , Tetzlaff Christian
Published: October 2019

In the course of everyday life, the brain must store and recall a huge variety of representations of stimuli which are presented in an ordered or sequential way. The processes by which the ordering of these various things is stored and recalled are moderately well understood. We use here a computational model of a cortex-like recurrent neural network adapted by a multitude of plasticity mechanisms. We first demonstrate the learning of a sequence. Then, we examine the influence of different types of distractors on the network dynamics during the recall of the encoded ordered information being ordered in a sequence. We are able to broadly arrive at two distinct effect-categories for distractors, arrive at a basic understanding of why this is so, and predict what distractors will fall into each category.
Weak Acid Resistance A (WarA), a novel transcription factor required for regulation of weak-acid resistance and spore-spore heterogeneity inAspergillus niger
Authors: Geoghegan Ivey A. , Stratford Malcolm , Bromley Mike , Archer David B. , Avery Simon V.
Published: October 2019

Propionic, sorbic and benzoic acids are organic weak acids that are widely used as food preservatives, where they play a critical role in preventing microbial growth. In this study, we uncovered new mechanisms of weak acid resistance in moulds. By screening a library of 401 transcription-factor deletion strains inAspergillus fumigatusfor sorbic acid hypersensitivity, a previously uncharacterised transcription factor was identified, and named as WarA (Weak Acid Resistance A). The orthologous gene in the spoilage mouldAspergillus nigerwas identified and deleted. WarA was required for resistance to a range of weak acids, including sorbic, propionic and benzoic acids. A transcriptomic analysis was performed to characterise genes regulated by WarA during sorbic acid treatment inA. niger. Several genes were significantly upregulated in the wild type compared with a ΔwarAmutant, including genes encoding putative weak acid detoxification enzymes and transporter proteins. Among these was An14g03570, a putative ABC-type transporter which we found to be required for weak acid resistance inA. niger. We also show that An14g03570 is a functional homologue of theSaccharomyces cerevisiaeprotein Pdr12p, and therefore named as PdrA. Lastly, resistance to sorbic acid was found to be highly heterogeneous within genetically-uniform populations of ungerminatedA. nigerconidia, and we demonstrate thatpdrAis a determinant of this heteroresistance. This study has identified novel mechanisms of weak acid resistance inA. nigerwhich could help to inform and improve future food spoilage prevention strategies.

IMPORTANCE

Weak acids are widely used as food preservatives, as they are very effective at preventing growth of most species of bacteria and fungi. However, some species of moulds can survive and grow in the concentrations of weak acid employed in food and drink products, thereby causing spoilage with resultant risks for food security and health. Current knowledge of weak acid resistance mechanisms in these fungi is limited, especially in comparison to that in yeasts. We characterised gene functions in the spoilage mould speciesAspergillus nigerwhich are important for survival and growth in the presence of weak acid preservatives. Such identification of weak acid resistance mechanisms in spoilage moulds will help to design new strategies to reduce food spoilage in the future.
High-resolution proteomics identifies potential new markers of Zika and dengue infections
Authors: Allgoewer Kristina , Zhao Alice , Maity Shuvadeep , Lashua Lauren , Ramgopal Moti , Balkaran Beni N. , Liu Liyun , Arévalo Maria T. , Ross Ted M. , Choi Hyungwon , Ghedin Elodie , Vogel Christine
Published: October 2019

Distinguishing between Zika and dengue virus infections is critical for treatment and anticipation of complications. However, existing biomarkers have high error rates. To identify new potential diagnostic signatures, we used next-generation proteomics to profile 122 serum samples from 62 Zika or dengue patients. We quantified >500 proteins and identified 26 proteins that were significantly differentially expressed. These proteins typically function in infection and wound healing, with several also linked to pregnancy and brain. Integrating machine learning approaches, we used 7 proteins to predict ZIKV infection correctly in 72% of the cases, outperforming other tools. The three most predictive proteins were Platelet Factor 4 Variant 1, Fibrinogen Alpha, and Gelsolin. Finally, we showed that temporal changes in protein signatures from the same patient can disambiguate some diagnoses and serve as indicators for past infections. Taken together, we demonstrate that serum proteomics can be highly valuable to diagnose even challenging samples.
No evidence for a relationship between social closeness and similarity in resting-state functional brain connectivity in schoolchildren
Authors: McNabb Carolyn Beth , Burgess Laura Grace , Fancourt Amy , Mulligan Nancy , FitzGibbon Lily , Riddell Patricia , Murayama Kou
Published: October 2019

Previous research suggests that the proximity of individuals in a social network predicts how similarly their brains respond to naturalistic stimuli. However, the relationship between social connectedness and brain connectivity in the absence of external stimuli has not been examined. To investigate whether neural homophily between friends exists at rest we collected resting-state functional magnetic resonance imaging (fMRI) data from 68 school-aged girls, along with social network information from all pupils in their year groups (total 5,066 social dyads). Participants were asked to rate the amount of time they voluntarily spent with each person in their year group, and directed social network matrices and community structure were then determined from these data. No statistically significant relationships between social distance, community homogeneity and similarity of global-level resting-state connectivity were observed. Nor were we able to predict social distance using a machine learning technique (i.e. elastic net regression based on the local-level similarities in resting-state whole-brain connectivity between participants). Although neural homophily between friends exists when viewing naturalistic stimuli, this finding did not extend to functional connectivity at rest in our population. Instead, resting-state connectivity may be less susceptible to the influences of a person’s social environment.
SPARC: a method to genetically manipulate precise proportions of cells
Authors: Isaacman-Beck Jesse , Paik Kristine C. , Wienecke Carl F. R. , Yang Helen H. , Fisher Yvette E. , Wang Irving E. , Ishida Itzel G. , Maimon Gaby , Wilson Rachel I. , Clandinin Thomas R.
Published: October 2019

Many experimental approaches rely on controlling gene expression in select subsets of cells within an individual animal. However, reproducibly targeting transgene expression to specific fractions of a genetically-defined cell-type is challenging. We developedSparsePredictiveActivity throughRecombinaseCompetition (SPARC), a generalizable toolkit that can express any effector in precise proportions of post-mitotic cells inDrosophila. Using this approach, we demonstrate targeted expression of many effectors and apply these tools to calcium imaging of individual neurons and optogenetic manipulation of sparse cell populationsin vivo.
Mechanisms of activation and desensitization of full-length glycine receptor in membranes
Authors: Kumar Arvind , Basak Sandip , Rao Shanlin , Gicheru Yvonne , Mayer Megan L. , Sansom Mark S.P , Chakrapani Sudha
Published: October 2019

Glycinergic synapses play a central role in motor control and pain processing in the central nervous system. Glycine receptors (GlyR) are key players in mediating fast inhibitory neurotransmission at these synapses. While previous high-resolution structural studies have provided insights into the molecular architecture of GlyR, several mechanistic questions pertaining to channel function are still unknown. Here, we present Cryo-EM structures of the full-length GlyR protein reconstituted into lipid nanodiscs that are captured in the unliganded (closed) and glycine-bound (open and desensitized) conformations. A comparison of the three states reveals global conformational changes underlying GlyR channel gating. The functional state assignments were validated by molecular dynamics simulations of the structures incorporated in a lipid bilayer. Observed permeation events are in agreement with the anion selectivity of the channel and the reported single-channel conductance of GlyR. These studies establish the structural basis for gating, selectivity, and single-channel conductance of GlyR in a physiological environment.
CAP2 is a novel regulator of Cofilin in synaptic plasticity and Alzheimer’s disease
Authors: Pelucchi Silvia , Vandermeulen Lina , Pizzamiglio Lara , Aksan Bahar , Yan Jing , Konietzny Anja , Bonomi Elisa , Borroni Barbara , Rust Marco , Marino Daniele Di , Mikhaylova Marina , Mauceri Daniela , Antonucci Flavia , Gardoni Fabrizio , Luca Monica Di , Marcello Elena
Published: October 2019

Cofilin is one of the major regulators of actin dynamics in spines where it is required for structural synaptic plasticity. However, our knowledge of the mechanisms controlling Cofilin activity in spines remains still fragmented. Here, we describe the cyclase-associated protein 2 (CAP2) as a novel master regulator of Cofilin localization in spines. The formation of CAP2 dimers through its Cys32 is important for CAP2 binding to Cofilin and for normal spine actin turnover. The Cys32-dependent CAP2 homodimerization and association to Cofilin are triggered by long-term potentiation (LTP) and are required for LTP-induced Cofilin translocation into spines, spine remodeling and the potentiation of synaptic transmission. This mechanism is specifically affected in the hippocampus, but not in the superior frontal gyrus, of both Alzheimer’s Disease (AD) patients and APP/PS1 mice, where CAP2 is down-regulated and CAP2 dimer synaptic levels are reduced. In AD hippocampi, Cofilin preferentially associates with CAP2 monomer and is aberrantly localized in spines. Taken together, these results provide novel insights into structural plasticity mechanisms that are defective in AD.
Risky drinking and dual diagnosis in older people under a UK community old age psychiatry service
Authors: Rao Rahul
Published: October 2019

Purpose

The assessment of patterns in risky drinking and its association with dual diagnosis in community services for older people remains under-explored. The paper aims to discuss this issue.

Design/methodology/approach

Drinking risk using the Alcohol Use Disorders Identification Test (AUDIT) and the presence of co-existing mental disorders was examined in 190 people aged 65 and over.

Findings

In total, 24 per cent of drinkers drank above lower risk levels and 22 per cent reported binge drinking over the past 12 months. Those scoring 1 or more on the AUDIT were more likely to be male and to have greater cognitive impairment than non-drinkers and those reporting no past problems with alcohol.

Research limitations/implications

Given the limitations of the Mini Mental State Examination in the detection of alcohol related cognitive impairment (ARCI), the use of other cognitive screening instruments in larger study populations is also warranted.

Practical implications

Greater attention needs to be paid to the assessment of risky drinking in older male drinkers and those with cognitive impairment.

Originality/value

There is considerable scope for the routine detection of cognitive impairment and dementia in older people with alcohol use within mainstream mental health services, particularly in those with binge drinking. As ARCI is associated with loss of function and independence, early detection and intervention can improve health and social outcomes.
Centralized supply chain – Food Lord
Authors: Shaikh Abdul Rehman , Qazi Asad Ali
Published: October 2019

Learning outcomes

The learning outcomes are as follows: to understand the impact of external factors in supply chain operations planning; to understand the role of quantitative and qualitative data in supply chain decision-making especially in the restaurant industry; to assess the pros and cons of centralized and decentralized supply chain operations; and to evaluate different alternatives in supply chain planning, for best service level at minimum cost.

Case overview/synopsis

This case visualizes the planning of supply chain drivers and process improvement to enhance supply chain speed and flexibility. Asim Rizvi has recently joined as senior supply chain manager at Food Lord, a renowned chain of restaurants in Pakistan. As instructed by his CEO, Rizvi has to take a decision for centralization, or to continue the decentralization of supply chain operations at two of their highest selling branches. These two branches were located at a distance of 125 km from each other. The objective of supply chain operations’ consolidation was to minimize cost and further improve the service level. Rizvi was confused about the decision because any decision cannot be taken on the basis of cost and benefit analysis only. A 360-degree analysis and future requirements also play a vital role to decide about supply chain operations. The CEO was very excited to take this decision; that is why newly hired manager Rizvi was analyzing all the facts to reach a decision that would be best for their business. Centralized or decentralized supply chain decision was not easy because normally the business dynamics completely change due to unpredictable customer demand, unavailability of professional suppliers and unavailability of a strong information system, etc.

Complexity academic level

BBA and MBA

Supplementary materials

Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 9: Operations and Logistics.
BIM business value for asset owners through effective asset information management
Authors: Munir Mustapha , Kiviniemi Arto , Finnegan Stephen , Jones Stephen W.
Published: October 2019

Purpose

The purpose of this paper is to investigate the processes, tools and techniques of strategic asset information management (AIM) for built assets, and how the asset information content enhances the proficiency of asset managers to effectively manage their assets throughout their life cycle by utilising building information modelling (BIM) and asset management (AM) systems. For most asset managers, the problem is not the lack of information about their assets, but the abundance of it, and most especially the absence of established processes and protocols to effectively manage large sets of asset data. Therefore, it is crucial to develop a strategy to control and manage this information in order for asset managers to harness its potential and realise value from their organisation’s information assets..

Design/methodology/approach

A qualitative case study strategy was used to investigate the effective management of asset data in an AIM system. Seven sets of interviews were conducted and nine respondents were interviewed. These were analysed through qualitative thematic analysis using the NVivo software.

Findings

The paper identifies six dimensions of value that BIM contributes to AM, which are: management, commerce, efficiency, industry, user and technology value. Also, the paper demonstrates that there is real value to be derived by the asset owner from the effective management of asset information. The study highlights that the value of BIM is not inherent but would require many other processes to deliver value to the organisation.

Originality/value

The key value of the paper is that it identifies important techniques for managing asset data and how asset information is collected, organised, stored, controlled, analysed, secured, shared and reported within a virtual AIM system for strategic management-based decisions.
Comparison between thermal resistances of optimized water-based and gallium-based heat sinks using the genetic algorithm
Authors: Xiang Xiong , Fan Yu , Liu Wei , Fan Aiwu
Published: October 2019

Purpose

The purpose of this paper is to compare the thermal resistances between optimized gallium- and water-based heat sinks to show which one is superior.

Design/methodology/approach

Taking the thermal resistances of heat sinks as the goal function, an optimization process is programmed based on the genetic algorithm. The optimal channel/fin widths and the corresponding thermal resistances of gallium- and water-based heat sinks are obtained and compared with/without a laminar flow constraint. The analytic model and CFD method are applied in different situations to ensure sufficient accuracy.

Findings

The results show that in the laminar regime, the thermal resistance of optimized gallium-based heat sink is lower than the water-based counterpart in most cases, but the latter becomes better if it is long enough or the channel is sufficient high. Without the laminar constraint, the thermal resistance of the optimized gallium-based heat sink can be decreased by 33-45 per cent compared with the water-based counterparts. It is interesting to find that when the heat sink is long or the channel height is short, the optimal geometry of gallium-based heat sink is a mini gap.

Originality/value

This paper demonstrates that the cooling performance of gallium-based heat sink can be significantly improved by optimization without the laminar flow constraint.
Dynamic relationality toward congruence: a symbiotic solution to cross-cultural negotiations
Authors: Cheng Junjun
Published: October 2019

Purpose

This paper aims to advance an integrative perspective of dynamic relationality in negotiation research by providing a symbiotic solution to modeling the cultural adaptation process in intercultural negotiations.

Design/methodology/approach

Based on a solution-oriented symbiotic approach, the authors analyze negotiators’ combination strategy to propose the dynamic convergence of dyadic relational negotiation behavior (RNB) both as a descriptive framework and a prescriptive solution to behavioral congruence in intercultural negotiations. The authors use spreadsheet platform with artificial data input to simulate various RNB dynamics between negotiators.

Findings

The authors identify the research gap between the arelational, static paradigm in negotiation literature and the relational, dynamic reality in negotiation practices, develop a fourfold typology of the existing negotiation research and propose the construct of RNB. The authors simulate the dyadic dynamics of RNB in a symbiotic framework. Results illustrate varied dyadic patterns of convergent RNB dynamics, demonstrating the effectiveness of the symbiotic solution to achieving behavioral congruence under multiple conditions. Propositions are then presented to predict negotiators’ initial relational behavior, describe dyadic coevolution of RNB in intercultural negotiations and explicate the relevant chronic consequences regarding relational and economic capital.

Originality/value

This paper fills a significant knowledge gap in the extant cross-cultural negotiation literature by addressing dynamic behavioral adaptation through a relational lens. This symbiotic framework is both descriptive in its predictive capacity to simulate the complexity of non-linear negotiation environment, and prescriptive in its directive capacity to guide negotiators’ plan of action given each other’s observed behavior with a probability estimation.
Preserving or maneuvring leadership? Teacher unions’ strategies in Israeli educational regulation
Authors: Arielyi Nivi Gal , Tamir Emanuel
Published: October 2019

Purpose

The purpose of this paper is to examine why, despite the advantages they might gain by participating in regulation of teaching by law, Israeli teachers’ unions leaders abandoned the opportunity to obtain the right of regulation and instead preferred an ambiguous role.

Design/methodology/approach

This is a policy research study, involving documentary analysis, focusing on one specific bill and data from interviews with teachers’ union leaders and officials who participated in discussions on the bill, and/or in crucial negotiations concerning teaching regulation.

Findings

It was found that unions’ leaders preferred to leave the licensing process for teaching as an open-ended and constantly negotiable issue with their employer rather than assuming the role of gatekeeper, understanding that this gave them more space and power to maneuvre in future struggles. Consequently, only the Education Ministry determines who becomes a teacher.

Research limitations/implications

These findings can inform educational policy makers and stakeholders, by giving them a glimpse into policy considerations. New knowledge is offered for the development of theory concerning teaching profession regulation and involvement of the teacher unions in these processes.

Practical implications

Policy makers may re-evaluate their interests as stakeholders in the education system, when they try to shape the profession through regulation of those who seek to become teachers.

Originality/value

The research sheds light on a hidden part of the policy-making puzzle that most studies do not explore and educational leaders prefer not to discuss especially when there is no proof of achievement, nor a public crisis.