bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Information Theory of Developmental Pruning: Optimizing Global Network Architecture Using Local Synaptic Rules
Authors: Scholl Carolin , Rule Michael E. , Hennig Matthias H. 
Published: December 2020

AbstractDuring development, biological neural networks produce more synapses and neurons than needed. Many of these synapses and neurons are later removed in a process known as neural pruning. Why networks should initially be over-populated, and processes that determine which synapses and neurons are ultimately pruned, remains unclear. We study the mechanisms and significance of neural pruning in model neural network. In a deep Boltzmann machine model of sensory encoding, we find that (1) synaptic pruning is necessary to learn efficient network architectures that retain computationally-relevant connections, (2) pruning by synaptic weight alone does not optimize network size and (3) pruning based on a locally-available proxy for “sloppiness” based on Fisher Information allows the network to identify structurally important vs. unimportant connections and neurons. This locally-available measure of importance has a biological interpretation in terms of the correlations between presynaptic and postsynaptic neurons, and implies an efficient activity-driven pruning rule. Overall, we show how local activity-dependent synaptic pruning can solve the global problem of optimizing a network architecture. We relate these findings to biology as follows: (I) Synaptic over-production is necessary for activity-dependent connectivity optimization. (II) In networks that have more neurons than needed, cells compete for activity, and only the most important and selective neurons are retained. (III) Cells may also be pruned due to a loss of synapses on their axons. This occurs when the information they convey is not relevant to the target population.
Genomic surveillance of antimicrobial resistance shows cattle are a moderate source of multi-drug resistant non-typhoidalSalmonellain Mexico
Authors: Delgado-Suárez Enrique Jesús , Palós-Guitérrez Tania , Ruíz-López Francisco Alejandro , Pérez Cindy Fabiola Hernández , Ballesteros-Nova Nayarit Emérita , Soberanis-Ramos Orbelín , Méndez-Medina Rubén Danilo , Allard Marc W. , Rubio-Lozano María Salud 
Published: December 2020

AbstractMulti-drug resistant (MDR) non-typhoidalSalmonella(NTS) is a major public health concern globally. This study reports antibiotic susceptibility testing and genotypic antimicrobial resistance (AMR) profiles of NTS isolates from bovine lymph nodes (n=48) and ground beef (n=29). Furthermore, we compared genotypic AMR data of our isolates with those of publicly available NTS genomes from Mexico (n=1637). The probability of finding MDR isolates was higher in ground beef as compared to lymph nodes: χ2=12.0, P=0.0005. The most common resistant phenotypes involved tetracycline (40.3%), carbenicillin (26.0%), amoxicillin-clavulanic acid (20.8%), chloramphenicol (19.5%) and trimethoprim-sulfamethoxazole (16.9%), while over 55% of the isolates showed decreased susceptibility to ciprofloxacin and 26% were MDR. Occurrence of MDR isolates was strongly associated with NTS serovar (χ2=24.5, P<0.0001), with Typhimurium accounting for 40% of MDR strains. Most of these (9/10), carriedSalmonellagenomic island 1, which harbors multiple AMR genes (aadA2, blaCARB-2, floR, sul1, tetG) that confer a penta-resistant phenotype. Moreover, 100% of MDR isolates had mutations in theramRgene. Among public NTS isolates from foods and clinical cases in Mexico to date, those from cattle had the highest proportion of MDR genotypes. Our results suggest attaining significant improvements in AMR meat safety may require the identification and removal (or treatment) of product harboring MDR NTS, instead of screening forSalmonellaspp. or for isolates showing resistance to individual antibiotics. In that sense, massive integration of whole genome sequencing (WGS) technologies in AMR surveillance provides the shortest path to accomplish these goals.
Reproductive Compatibility inCapsicumis not Reflected in Genetic or Phenotypic Similarity Between Species Complexes
Authors: Parry Catherine , Wang Yen-wei , Lin Shih-wen , Barchenger Derek W. 
Published: December 2020

AbstractWild relatives of domesticatedCapsicumrepresent substantial genetic diversity and thus sources of traits of potential interest. Furthermore, the hybridization compatibility between members ofCapsicumspecies complexes remains unresolved. Improving our understanding of the relationship betweenCapsicumspecies relatedness and their ability to form hybrids is a highly pertinent issue. Through the development of novel interspecific hybrids in this study, we demonstrate interspecies compatibility is not necessarily reflected in relatedness according to establishedCapsicumgenepool complexes. Based on a phylogeny constructed by genotyping using single sequence repeat (SSR) markers and with a portion of thewaxylocus, and through principal component analysis (PCA) of phenotypic data, we clarify the relationships among wild and domesticatedCapsicumspecies. Together, the phylogeny and hybridization studies provide evidence for the misidentification of a number of species from the World Vegetable Center genebank included in this study. The World Vegetable Center holds the largest collection ofCapsicumgenetic material globally, therefore this may reflect a wider issue in the misidentification ofCapsicumwild relatives. The findings presented here provide insight into an apparent disconnect between compatibility and relatedness in theCapsicumgenus, which will be valuable in identifying candidates for future breeding programs.
Plasticity impairment alters community structure but permits successful pattern separation in a hippocampal network model
Authors: Schumm Samantha N. , Gabrieli David , Meaney David F. 
Published: December 2020

AbstractPatients who suffer from traumatic brain injury (TBI) often complain of learning and memory problems. Their symptoms are principally mediated by the hippocampus and the ability to adapt to stimulus, also known as neural plasticity. Therefore, one plausible injury mechanism is plasticity impairment, which currently lacks comprehensive investigation across TBI research. For these studies, we used a computational network model of the hippocampus that includes the dentate gyrus, CA3, and CA1 with neuron-scale resolution. We simulated mild injury through weakened spike-timing-dependent plasticity (STDP), which modulates synaptic weights according to causal spike timing. In preliminary work, we found functional deficits consisting of decreased firing rate and broadband power in areas CA3 and CA1 after STDP impairment. To address structural changes with these studies, we applied modularity analysis to evaluate how STDP impairment modifies community structure in the hippocampal network. We also studied the emergent function of network-based learning and found that impaired networks could acquire conditioned responses after training, but the magnitude of the response was significantly lower. Furthermore, we examined pattern separation, a prerequisite of learning, by entraining two overlapping patterns. Contrary to our initial hypothesis, impaired networks did not exhibit deficits in pattern separation with either population- or rate-based coding. Collectively, these results demonstrate how a mechanism of injury that operates at the synapse regulates circuit function.Author summaryTraumatic brain injury causes diverse symptoms, and memory problems are common among patients. These deficits are associated with the hippocampus, a brain region involved in learning and memory. Neural plasticity supports learning and memory by enabling the circuit to adapt to external stimulus. After brain injury, plasticity can be impaired, perhaps contributing to memory deficits. Yet, this mechanism of injury remains poorly understood. We implemented plasticity impairment and learning in a network model of the hippocampus that is unique because it has a high degree of biological detail in its structure and dynamics compared to other similar computational models. First, we examined the relationship between neurons in the network and characterized how the structure changed with injury. Then we trained the network with two input patterns to test the function of pattern separation, which is the ability to distinguish similar contexts and underpins general learning. We found that the strength of the encoded response decreased after impairment, but the circuit could still distinguish the two input patterns. This work provides insight into which specific aspects of memory become dysfunctional after injury.
Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type
Authors: Contreras Susana Andrea , Schleimer Jan-Hendrik , Gulledge Allan T. , Schreiber Susanne 
Published: December 2020

AbstractDuring normal neuronal activity, ionic concentration gradients across a neuron’s membrane are often assumed to be stable. Prolonged spiking activity, however, can reduce transmembrane gradients and affect voltage dynamics. Based on mathematical modeling, we investigated the impact of neuronal activity on ionic concentrations and, consequently, the dynamics of action potential generation. We find that intense spiking activity on the order of a second suffices to induce changes in ionic reversal potentials and to consistently induce a switch from a regular to an intermittent firing mode. This transition is caused by a qualitative alteration in the system’s voltage dynamics, mathematically corresponding to a co-dimension-two bifurcation from a saddle-node on invariant cycle (SNIC) to a homoclinic orbit bifurcation (HOM). Our electrophysiological recordings in mouse cortical pyramidal neurons confirm the changes in action potential dynamics predicted by the models: (i) activity-dependent increases in intracellular sodium concentration directly reduce action potential amplitudes, an effect typically attributed solely to sodium channel inactivation; (ii) extracellular potassium accumulation switches action potential generation from tonic firing to intermittently interrupted output. Thus, individual neurons may respond very differently to the same input stimuli, depending on their recent patterns of activity and/or the current brain-state.Author summaryIonic concentrations in the brain are not constant. We show that during intense neuronal activity, they can change on the order of seconds and even switch neuronal spiking patterns under identical stimulation from a regular firing mode to an intermittently interrupted one. Triggered by an accumulation of extracellular potassium, such a transition is caused by a specific, qualitative change in of the neuronal voltage dynamics – a so-called bifurcation – which affects crucial features of action-potential generation and bears consequences for how information is encoded and how neurons behave together in the network. Also, changes in intracellular sodium can induce measurable effects, like a shrinkage of spike amplitude that occurs independently of the fast amplitude-effects attributed to sodium channel inactivation. Taken together, our results demonstrate that a neuron can respond very differently to the same stimulus, depending on its previous activity or the current brain state. This finding may be particularly relevant when other regulatory mechanisms of ionic homeostasis are challenged, for example, during pathological states of glial impairment or oxygen deprivation. Finally, Categorization of cortical neurons as intrinsically bursting or regular spiking may be biased by the ionic concentrations at the time of the observation, highlighting the non-static nature of neuronal dynamics.
p38-MAPK mediated rRNA processing and translation regulation enables PrE differentiation during mouse blastocyst maturation
Authors: Bora Pablo , Gahurova Lenka , Mašek Tomáš , Hauserova Andrea , Potěšil David , Jansova Denisa , Susor Andrej , Zdráhal Zbyněk , Ajduk Anna , Pospíšek Martin , Bruce Alexander W. 
Published: December 2020

AbstractBackgroundp38-MAPKs are stress-activated kinases necessary for placental development and nutrient and oxygen transfer during murine post-implantation development. In preimplantation development, p38-MAPK activity is required for blastocyst formation. Additionally, we have previously reported its role in regulating specification of inner cell mass (ICM) towards primitive endoderm (PrE), although a comprehensive mechanistic understanding is currently limited. Adopting live embryo imaging, proteomic and transcriptomic approaches, we report experimental data that directly address this deficit.ResultsChemical inhibition of p38-MAPK activity during blastocyst maturation causes impaired blastocyst cavity expansion, most evident between the third and tenth hours post inhibition onset. We identify an overlapping minimal early blastocyst maturation window of p38-MAPKi inhibition (p38-MAPKi) sensitivity, that is sufficient to impair PrE cell fate by the late blastocyst (E4.5) stage. Comparative proteomic analyses reveal substantial downregulation of ribosomal proteins, the mRNA transcripts of which are also significantly upregulated. Ontological analysis of the differentially expressed transcriptome during this developmental period reveals “translation” related gene transcripts as being most significantly, yet transiently, affected by p38-MAPKi. Moreover, combined assays consistently report concomitant reductions inde novotranslation that are associated with accumulation of unprocessed rRNA precursors. Using a phosphoproteomic approach, ± p38-MAPKi, we identifiedMybpp1a,an rRNA transcription and processing regulator gene, as a potential p38-MAPK effector. We report that siRNA mediated clonal knockdown ofMybpp1ais associated with significantly diminished PrE contribution. Lastly, we show that defective PrE specification caused by p38-MAPKi (but not MEK/ERK signalling inhibition) can be partially rescued by activating the archetypal mTOR mediated translation regulatory pathway.ConclusionsActivated p38-MAPK controls blastocyst maturation in an early and distinctly transient developmental window by regulating gene functionalities related to translation, that creates a permissive environment for appropriate specification of ICM cell fate.
Aberrant structural synaptic dynamics precede disorganization of temporal and spatial coding in the hippocampus upon repeated stress exposure
Authors: Chenani Alireza , Weston Ghabiba , Ulivi Alessandro F. , Castello-Waldow Tim P. , Chen Alon , Attardo Alessio 
Published: December 2020

ABSTRACTStress exposure strongly contributes to the pathophysiology of psychiatric diseases such as depression, schizophrenia, anxiety, and post-traumatic stress disorder. It also affects both function and structure of hippocampal CA1, leading to episodic memory impairment. Here, we used deep-brain optical imaging to elucidate the effects of stress on CA1 pyramidal neuron structural connectivity and activity.We tracked dynamics of dendritic spines during repeated stress and found decrease in spinogenesis followed by decrease in spine stability. In contrast to repeated stress, acute stress led to stabilization of the spines born in temporal proximity to the stressful event. To investigate the link between structural plasticity and activity patterns upon repeated stress, we studied the activity of thousands of CA1 pyramidal neurons in freely-moving. We found an increase in activity and loss of temporal organization followed by a disruption in temporal and spatial coding. Our data suggest that stress-induced sustained increase in activity leads to loss of structural connectivity and subsequent temporal and spatial coding impairments.
pH Effect on the Dynamics of SARS-CoV-2 Main Protease (Mpro)
Authors: Sharma Shilpa , Deep Shashank 
Published: December 2020

AbstractThe SARS-CoV-2 main protease (Mpro) is a crucial enzyme responsible for the maturation of novel coronavirus, thus it serves as an excellent target for drug discovery. SARS-CoV-2 is found to have similarity with SARS-CoV, which showed conformational changes upon varying pH. There is no study till date on how pH change affect the conformtional flexibilty of SARS-CoV-2 Mpro, therefore, we attempt to find the effect of pH variation through constant pH molecular dynamics simulation studies. Protein is found to be most stable at neutral pH and as pH turns basic protein structure becomes most destabilized. Acidic pH also tends to change the structural properties of Mpro. Our study provides evidence that the flexibility of Mprois pH dependent like SARS-CoV Mpro.
Virophages and retrotransposons colonize the genomes of a heterotrophic flagellate
Authors: Hackl Thomas , Duponchel Sarah , Barenhoff Karina , Weinmann Alexa , Fischer Matthias G. 
Published: December 2020

AbstractVirophages can parasitize giant DNA viruses and may provide adaptive anti-giant-virus defense in unicellular eukaryotes. Under laboratory conditions, the virophage mavirus integrates into the nuclear genome of the marine flagellateCafeteria burkhardaeand reactivates upon superinfection with the giant virus CroV. In natural systems, however, the prevalence and diversity of host-virophage associations has not been systematically explored. Here, we report dozens of integrated virophages in four globally sampledC. burkhardaestrains that constitute up to 2% of their host genomes. Theseendogenousmavirus-likeelements (EMALEs) separated into eight types based on GC-content, nucleotide similarity, and coding potential and carried diverse promoter motifs implicating interactions with different giant viruses. Between host strains, some EMALE insertion loci were conserved indicating ancient integration events, whereas the majority of insertion sites were unique to a given host strain suggesting that EMALEs are active and mobile. Furthermore, we uncovered a unique association between EMALEs and a group of tyrosine recombinase retrotransposons, revealing yet another layer of parasitism in this nested microbial system. Our findings show that virophages are widespread and dynamic in wildCafeteriapopulations, supporting their potential role in antiviral defense in protists.
An analysis of factors that influence the decision to export: perspective of Brazilian companies
Authors: Mataveli Mara , Ayala Juan Carlos , Gil Alfonso J. 
Published: December 2020

PurposeThe objective of this work is to examine the factors that influence the decision of Brazilian companies to export.Design/methodology/approachA questionnaire was used to collect data from a statistically significant sample of 318 Brazilian exporting firms. Three types of study were carried out; an exploratory study that simplified the information through a principal component analysis, a descriptive study of the factors that influence the decision to export by Brazilian companies and a study of variance that allowed comparison of groups of firms.FindingsAfter an analysis of the literature, 11 factors were proposed that influence the decision to export. Two unique factors resulted from the principal components analysis: “resource optimisation” and “performance and development”. The “performance and development” factor was more valued than the “resource optimisation” factor. From the analysis of variance, significant differences were only found in the variable “firm size”.Originality/valueThis paper contributes to the literature by presenting further knowledge of export factors in developing countries, the management of companies and instruments for decision making in the area of internationalisation.
Faysal Asset Management mutual funds performance evaluation
Authors: Kumar Vikesh , Bhayo Mujeeb-U-Rehman , Kumar Sundeep , Kumar Rakesh , Dakhan Sarfraz Ahmed 
Published: December 2020

Learning outcomes
The learning outcomes are as follows: to teach the concept of mutual fund as whole, how mutual fund works and who are the investors; discuss how any asset management company can work and what is their investment process; discuss how mutual funds are affected by changes in economic outlook/macro-economic variables; discuss the alternative risk-adjusted measures of performance evaluation, such as the Sharpe ratio, Treynor, Jensen’s alpha and measure of risk-adjusted performance; and discuss which index to use as a benchmark and how to improve funds’ performance.

Case overview/synopsis
In April 2019, Khaldoon Bin latif, Chief Executive Officer (CEO) of Faysal Asset Management, reflected on the changes that had occurred during his two and a half years at Faysal. He was quite pleased with the recent performance of Faysal Funds and the company’s relationship-oriented approach to money management for individuals with high net worth. Yet, he wanted to ensure that both the investment-process and performance-evaluation measures that he had implemented at Faysal would continue to provide superior returns. Latif also wanted Faysal to outperform the relevant indices, not only on an absolute basis, but also on a risk-adjusted basis. He pondered which indices and models Faysal should use in the future based on their performance.

Complexity academic level
Undergraduate/graduate

Supplementary materials
Teaching Notes are available for educators only.

Subject code
CSS 1: Accounting and Finance.
Economic policy uncertainty and house prices in Germany: evidence from GSADF and wavelet coherence techniques
Authors: Kirikkaleli Dervis , Gokmenoglu Korhan , Hesami Siamand 
Published: December 2020

PurposeThis study aims to answer the following questions which have not been investigated in the literature to the best knowledge: Is there any bubble in the German housing sector between 2005–2009 and 2012–2017? and Is there any linkage between economic policy uncertainty and the housing sector price index?Design/methodology/approachThis study aims to shed some light on the German’s housing sector by investigating the housing sector bubble and the causal link between the housing sector index and economic policy uncertainty in Germany, using GSADF, Granger causality, Toda Yamamoto causality and wavelet coherence tests.FindingsThe findings reveal that there are some bubbles in the housing sector in Germany for the periods investigated, there is a positive correlation between economic policy uncertainty and housing sector price index at different frequencies and different periods and between 2008 and 2009 and between 2011 and 2013, economic policy uncertainty leads housing sector price index. The consistency of the findings from wavelet coherence is confirmed by the outcomes of Granger causality and Toda Yamamoto causality tests.Originality/valueTo the best knowledge, this is the first study that empirically investigates the relationship between the housing sector and EPU using a novel wavelet econometric method. In addition, this paper extends the research focused on the associations between the housing sector and EPU, by checking the bubbles in the market in different time horizons by using the longest available data span. Furthermore, the consistency of the findings from wavelet causality is confirmed by the outcomes of Granger causality and Toda Yamamoto causality tests. Finally, compared to the previous literature on the relationship between housing and EPU, the study uses a hedonic index for housing for the first time in the case of Germany.