bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling motor-evoked potentials from neural field simulations of transcranial magnetic stimulation
Authors: Wilson Marcus T , Moezzi Bahar , Rogasch Nigel C
Published: November 2019

Objective

To develop a population-based biophysical model of motor-evoked potentials (MEPs) following transcranial magnetic stimulation (TMS).

Methods

We combined an existing MEP model with population-based cortical modeling. Layer 2/3 excitatory and inhibitory neural populations, modeled with neural-field theory, are stimulated with TMS and feed layer 5 corticospinal neurons, which also couple directly but weakly to the TMS pulse. The layer 5 output controls mean motoneuron responses, which generate a series of single motor-unit action potentials that are summed to estimate a MEP.

Results

A MEP waveform was generated comparable to those observed experimentally. The model captured TMS phenomena including a sigmoidal input-output curve, common paired pulse effects (short interval intracortical inhibition, intracortical facilitation, long interval intracortical inhibition) including responses to pharmacological interventions, and a cortical silent period. Changes in MEP amplitude following theta burst paradigms were observed including variability in outcome direction.

Conclusions

The model reproduces effects seen in common TMS paradigms.

Significance

The model allows population-based modeling of changes in cortical dynamics due to TMS protocols to be assessed in terms of changes in MEPs, thus allowing a clear comparison between population-based modeling predictions and typical experimental outcome measures.

Highlights

A model of motor-evoked potential formation gives a realistic electromyogram in response to TMS.

The model reproduces effects of SICI, ICF and LICI.

A link between existing neural field modeling and realistic outcome measures of TMS is provided.
Pharmacological complementation remedies an inborn error of lipid metabolism
Authors: Hartley Meredith D. , Shokat Mitra D. , DeBell Margaret J. , Banerji Tania , Kirkemo Lisa L. , Scanlan Thomas S.
Published: November 2019

X-linked adrenoleukodystrophy (X-ALD) is a rare, genetic disease in which increased very long chain fatty acids (VLCFAs) in the central nervous system (CNS) cause demyelination and axonal degeneration, leading to severe neurological deficits. Sobetirome, a potent thyroid hormone agonist, has been shown to lower VLCFA levels in the periphery and CNS. In this study, two pharmacological strategies for enhancing the effects of thyromimetics were tested in Abcd1 KO mice, a murine model that has the same inborn error in metabolism as X-ALD patients. First, a sobetirome prodrug (Sob-AM2) with increased CNS penetration lowered CNS VLCFAs more potently than sobetirome, and was better tolerated with lower peripheral exposure, but was unable to unable to break the efficacy threshold of CNS VLCFA lowering in Abcd1 KO mice. Second, co-administration of thyroid hormone with sobetirome enhanced VLCFA lowering in the periphery compared to sobetirome alone but did not produce greater lowering in the CNS. These data suggest that the extent of CNS VLCFA lowering in Abcd1 KO mice is limited by a mechanistic threshold related to slow turnover kinetics, potentially related to the lack of frank X-ALD disease in this model. However, Sob-AM2 has improved potency at correcting the lipid abnormality associated with X-ALD in the CNS with better tolerance than the parent drug sobetirome.
Automated cot-side tracking of functional brain age in preterm infants
Authors: Stevenson Nathan J. , Oberdorfer Lisa , Tataranno Maria-Luisa , Breakspear Michael , Colditz Paul B. , de Vries Linda S. , Benders Manon J. N. L. , Klebermass-Schrehof Katrin , Vanhatalo Sampsa , Roberts James A.
Published: November 2019

Objective

A major challenge in the care of preterm infants is the early identification of compromised neurological development. While several measures are routinely used to track anatomical growth, there is a striking lack of reliable and objective tools for tracking maturation of early brain function; a cornerstone of lifelong neurological health. We present a cot-side method for measuring the functional maturity of the newborn brain based on routinely-available neurological monitoring with electroencephalography (EEG).

Methods

We used a dataset of 177 EEG recordings from 65 preterm infants to train a multivariable prediction of functional brain age (FBA) from EEG. The FBA was validated on an independent set of 99 EEG recordings from 42 preterm infants. The difference between FBA and postmenstrual age (PMA) was evaluated as a predictor for neurodevelopmental outcome.

Results

The FBA correlated strongly with the PMA of an infant, with a median prediction error of less than 1 week. Moreover, individual babies follow well-defined individual trajectories. The accuracy of the FBA applied to the validation set was statistically equivalent to the training set accuracy. In a subgroup of infants with repeated EEG recordings, a persistently negative predicted age difference was associated with poor neurodevelopmental outcome.

Interpretation

The FBA enables the tracking of functional neurodevelopment in preterm infants. This establishes proof of principle for growth charts for brain function, a new tool to assist clinical management and identify infants who will benefit most from early intervention.
Fungal communities (Mycobiome) as potential ecological indicators within confluence stretch of Ganges and Yamuna Rivers, India
Authors: Samson Rachel , Rajput Vinay , Shah Manan , Yadav Rakeshkumar , Sarode Priyanka , Dastager Syed G. , Dharne Mahesh S. , Khairnar Krishna
Published: November 2019

River confluences are a hub of biodiversity with limited information with respect to the structure and the functions of the microbial communities. The ‘River Ganges’ is the national river of India, having manifold significance such as social, mythological, historic, geographic and agro-economic. It forms a sacred confluence (known asTriveni Sangam) with River Yamuna at Prayagraj, India. Recent reports indicated the presence of fecal coliform bacteria, an indicator recognized for water contamination in Ganges River leading to pollution. However, Fungi are also gaining attention as potential biological indicators of the trophic status of some rivers globally, but remain under-explored in terms of diversity, ecology and functional aspects. We performed whole long read, metagenome sequencing (MinION) of the sediment samples collected in December 2017 from confluence zone of Ganges and Yamuna Rivers spanning the pre-confluence, confluence and post-confluence zones. Mycobiome reads revealed a plethora of fungal communities, extending from saprophytes, endoparasites and edible fungi, to human pathogens, plant pathogens and toxin producers. The fungal genera recognized as bio-indicators of river pollution (Aspergillus,Penicillium) and eutrophication (Kluveromyces,Lodderomyces, andNakaseomyces), were present in all samples. Functional gene analyses of myco-communities uncovered hits for neurodegenerative diseases and xenobiotic degradation potential, supporting bio-indicators of pollution. This study forms a foundational basis for understanding the impact of various anthropogenic activities on the mycobiome, as a bio-indicator of pollution across the confluence of Ganges and Yamuna Rivers and post-confluence of River Ganges, and could be useful in mitigating strategies for cleaning strategies of the Ganges River.
Long read sequencing of 3,622 Icelanders provides insight into the role of structural variants in human diseases and other traits
Authors: Beyter Doruk , Ingimundardottir Helga , Oddsson Asmundur , Eggertsson Hannes P. , Bjornsson Eythor , Jonsson Hakon , Atlason Bjarni A. , Kristmundsdottir Snaedis , Mehringer Svenja , Hardarson Marteinn T. , Gudjonsson Sigurjon A. , Magnusdottir Droplaug N. , Jonasdottir Aslaug , Jonasdottir Adalbjorg , Kristjansson Ragnar P. , Sverrisson Sverrir T. , Holley Guillaume , Palsson Gunnar , Stefansson Olafur A. , Eyjolfsson Gudmundur , Olafsson Isleifur , Sigurdardottir Olof , Torfason Bjarni , Masson Gisli , Helgason Agnar , Thorsteinsdottir Unnur , Holm Hilma , Gudbjartsson Daniel F. , Sulem Patrick , Magnusson Olafur T. , Halldorsson Bjarni V. , Stefansson Kari
Published: November 2019

Long-read sequencing (LRS) promises to improve characterization of structural variants (SVs), a major source of genetic diversity. We generated LRS data on 3,622 Icelanders using Oxford Nanopore Technologies, and identified a median of 22,636 SVs per individual (a median of 13,353 insertions and 9,474 deletions), spanning a median of 10 Mb per haploid genome. We discovered a set of 133,886 reliably genotyped SV alleles and imputed them into 166,281 individuals to explore their effects on diseases and other traits. We discovered an association with a rare (AF = 0.037%) deletion of the first exon ofPCSK9. Carriers of this deletion have 0.93 mmol/L (1.31 SD) lower LDL cholesterol levels than the population average (p-value = 7.0·10−20). We also discovered an association with a multi-allelic SV inside a large repeat region, contained within single long reads, in an exon ofACAN. Within this repeat region we found 11 alleles that differ in the number of a 57 bp-motif repeat, and observed a linear relationship (0.016 SD per motif inserted, p = 6.2·10−18) between the number of repeats carried and height. These results show that SVs can be accurately characterized at population scale using long read sequence data in a genome-wide non-targeted approach and demonstrate how SVs impact phenotypes.
Disentangling functional connectivity effects of age and expertise in long-term meditators
Authors: Guidotti Roberto , Gratta Cosimo Del , Perrucci Mauro Gianni , Romani Gian Luca , Raffone Antonino
Published: November 2019

The effects of intensive meditation practices on the functional and structural organization of the human brain have been addressed by a growing number of neuroscientific studies. However, the different modulations of meditation expertise and of ageing, in the underlying brain areas and networks, have not yet been fully elucidated. These effects should be distinguished in order to clarify how long-term meditation can modulate the connectivity between brain areas. To address this issue, we tested whether meditation expertise and age can be predicted from the multivariate pattern of functional Magnetic Resonance Imaging connectivity, in Theravada Buddhist monks with long-term practice in two different meditation forms: Focused Attention (FA) and Open Monitoring (OM).

We found that functional connectivity patterns in both meditation forms can be used to predict expertise and age of long-term meditators. Our findings suggest that meditation expertise is associated with meditation-specific brain networks modulations, while age-related modifications are general and independent from the meditation type. Specifically, expertise modulated patterns during FA meditation include nodes and connections implicated in focusing, sustaining and monitoring attention, while the predictive patterns during OM meditation include nodes associated with cognitive and affective monitoring. Thus, the two forms of meditation may differentially contribute to counteract the effects of neurocognitive decline with ageing by neuroplasticity of brain networks.
Large male proboscis monkeys have larger noses but smaller canines
Authors: Matsuda Ikki , Stark Danica J. , Ramirez Saldivar Diana A. , Tuuga Augustine , Nathan Senthilvel K. S. S. , Goossens Benoit , van Schaik Carel P. , Koda Hiroki
Published: November 2019

The uniquely enlarged noses of male proboscis monkeys are prominent adornments, and a sexually selected male trait. A recent study showed significant correlations among nose, body, and testis sizes and clear associations between nose size and the number of females in a male’s harem. However, to date, the analyses of other common male traits, i.e., canines, are lacking. Whereas male nose size had a positive correlation with body size, we unexpectedly found a negative correlation between body and canine sizes. We explain this by an interaction between sexual and natural selection. Larger noses in males may interfere with the use of canines, thereby reducing their effectiveness as weapons. Additionally, longer canines are opposed by natural selection because the larger gape it imposes upon its bearer reduces foraging efficiency, particularly in folivores. This unique case of decoupling of body and canine size reveals that large canines carry an ecological cost.
Acclimation, priming and memory in the response ofArabidopsis thalianaseedlings to cold stress
Authors: Leuendorf Jan Erik , Frank Manuel , Schmülling Thomas
Published: November 2019

Because stress experiences are often recurrent plants have developed strategies to remember a first so-called priming stress to eventually respond more effectively to a second triggering stress. Here, we have studied the impact of discontinuous or sustained cold stress (4 °C) onin vitrogrownArabidopsis thalianaseedlings of different age and their ability to get primed and respond differently to a later triggering stress. Cold treatment of 7-d-old seedlings induced the expression of cold response genes but did not cause a significantly enhanced freezing resistance. The competence to increase the freezing resistance in response to cold was associated with the formation of true leaves. Discontinuous exposure to cold only during the night led to a stepwise modest increase in freezing tolerance provided that the intermittent phase at ambient temperature was less than 32 h. Seedlings exposed to sustained cold treatment developed a higher freezing tolerance which was further increased in response to a triggering stress during three days after the priming treatment had ended indicating cold memory. Interestingly, in all scenarios the primed state was lost as soon as the freezing tolerance had reached the level of naïve plants indicating that an effective memory was associated with an altered physiological state. Known mutants of the cold stress response (cbfs, erf105) and heat stress memory (fgt1) did not show an altered behaviour indicating that their roles do not extend to memory of cold stress.
Statistical inference of mechanistic models from qualitative data using an efficient optimal scaling approach
Authors: Schmiester Leonard , Weindl Daniel , Hasenauer Jan
Published: November 2019

Quantitative dynamical models facilitate the understanding of biological processes and the prediction of their dynamics. These models usually comprise unknown parameters, which have to be inferred from experimental data. For quantitative experimental data, there are several methods and software tools available. However, for qualitative data the available approaches are limited and computationally demanding.

Here, we consider the optimal scaling method which has been developed in statistics for categorical data and has been applied to dynamical systems. This approach turns qualitative variables into quantitative ones, accounting for constraints on their relation. We derive a reduced formulation for the optimization problem defining the optimal scaling. The reduced formulation possesses the same optimal points as the established formulation but requires less degrees of freedom. Parameter estimation for dynamical models of cellular pathways revealed that the reduced formulation improves the robustness and convergence of optimizers. This resulted in substantially reduced computation times.

We implemented the proposed approach in the open-source Python Parameter EStimation TOolbox (pyPESTO) to facilitate reuse and extension. The proposed approach enables efficient parameterization of quantitative dynamical models using qualitative data.
Early vocal production and functional flexibility in wild infant chimpanzees
Authors: Dezecache Guillaume , Zuberbühler Klaus , Davila-Ross Marina , Dahl Christoph D.
Published: November 2019

How did human language evolve from earlier forms of communication? One way to address this question is to compare prelinguistic human vocal behavior with nonhuman primate calls. Here, an important finding has been that, prior to speech, human infant vocal behavior exhibits functional flexibility, the capacity of producing protophones that are not tied to one specific function. Nonhuman primate vocal behavior, by contrast, is comparably inflexible, with different call types tied to specific functions. Our research challenges the generality of this claim, with new findings of flexible vocal behavior in infant chimpanzees. We used artificial intelligence consisting of automated feature extraction and supervised learning algorithms to analyze grunt and whimper vocalizations from free-ranging infants during their first year of life. We found that grunt production was highly flexible occurring in positive, neutral and negative circumstances, as already shown in human infants. We also found acoustic variants of grunts produced in different affective contexts, suggesting gradation within this vocal category. By contrast, the second most common call type of infant chimpanzees, the whimpers, was produced in only one affective context in line with standard models of nonhuman primate vocal behavior. We concluded that the most common chimpanzee vocalization, the grunt, qualifies as functionally flexible, suggesting that evolution of vocal functional flexibility occurred before the split between the Homo and Pan lineages.
Cryptic, solo acylhomoserine lactone synthase from predatory myxobacterium suggests beneficial contribution to prey quorum signaling
Authors: Albataineh Hanan , Duke Maya , Misra Sandeep K. , Sharp Joshua S. , Stevens D. Cole
Published: November 2019

Considered a key taxon in microbial communities, myxobacteria exist as coordinated swarms that utilize an excreted combination of lytic enzymes and specialized metabolites to facilitate predation of numerous microbial phyla. This capacity to produce biologically active metabolites and the associated abundance of natural product biosynthetic pathways contained within their genomes have motivated continued drug discovery efforts from myxobacteria. Of all the biosynthetic gene clusters associated with myxobacteria deposited in the antiSMASH database (∼1,000 total), only one putative acylhomoserine lactone synthase, agpI, was observed in genome data from the myxobacterium Archangium gephyra. Without an acylhomoserine lactone (AHL) receptor also apparent in the genome of A. gephyra, we sought to determine if AgpI was the first example of an orphaned AHL synthase. Herein we report the bioinformatic assessment of AgpI and discovery of a second myxobacterial AHL synthase from Vitiosangium sp. strain GDMCC 1.1324. During axenic cultivation conditions, no detectible AHL metabolites were observed in A. gephyra extracts. However, heterologous expression of each synthase in Escherichia coli provided detectible quantities of 3 AHL signals including 2 known AHLs, C8-AHL and C9-AHL. These results suggest that A. gephyra AHL production is dormant during axenic cultivation conditions and requires an unknown external cue for activation. The orphaned AHL synthase, AgpI, is the first to be reported from a predatory myxobacterium, and predator production of prey quorum signals provides unique insight into interspecies crosstalk within polymicrobial communities.

Importance

The presence of orphaned quorum signal receptors and associated recognition and response to exogenous acylhomoserine lactone quorum signals observed in microbial communities provides evidence for small molecule-mediated interspecies interactions. While the high occurrence of orphaned AHL receptors from bacteria that do not produce cognate AHL signals suggests the involvement of AHL signals as a shared chemical resource in polymicrobial communities, no orphaned AHL synthases have been determined to be functional in a species without an associated AHL receptor. An orphan signal synthase from a predatory myxobacterium provides an alternative perspective on the evolution and benefits of quorum signaling systems within these communities.
IQ-TREE 2: New models and efficient methods for phylogenetic inference in the genomic era
Authors: Minh Bui Quang , Schmidt Heiko , Chernomor Olga , Schrempf Dominik , Woodhams Michael , von Haeseler Arndt , Lanfear Robert
Published: November 2019

IQ-TREE (http://www.iqtree.org) is a user-friendly and widely used software package for phylogenetic inference using maximum likelihood. Since the release of version 1 in 2014, we have continuously expanded IQ-TREE to integrate a plethora of new models of sequence evolution and efficient computational approaches of phylogenetic inference to deal with genomic data. Here, we describe notable features of IQ-TREE version 2 and highlight the key advantages over other software.
Midgut aminopeptidase N expression profile in Castor semilooper during sublethal Cry toxin exposure
Authors: Chauhan Vinod K. , Dhania Narender K. , Lokya Vadthya , Bhuvanachandra Bhoopal , Padmasree Kollipara , Dutta-Gupta Aparna
Published: November 2019

Midgut of lepidopteran larvae is a multifunctional tissue, which performs roles in digestion, absorption, immunity; transmission of pathogens and interaction with ingested various molecules. The proteins localized at the inner apical brush border membrane are primarily digestive proteases but some of them like aminopeptidase N, alkaline phosphatase, cadherins, ABC transporter C2 etc. interact with Crystal (Cry) toxins produced by Bacillus thuringiensis (Bt). In the present study aminopeptidase N (APN) was characterized as Cry toxin interacting protein in larval midgut of castor semilooper, Achaea janata. Transcriptomic and proteomic analyses revealed the presence of multiple isoforms of APNs (APN1, 2, 4, 6 and 9) which have less than 40% sequence similarity but show the presence of characteristic “GAMENEG” and zinc-binding motifs. Feeding of sublethal dose of Cry toxin caused differential expression of various APN isoform. Further, 6th generation Cry toxin exposed larvae showed reduced expression of APN2. This report suggests that A. janata larvae exploit altered expression of APNs to overcome the deleterious effects of Cry toxicity, which might facilitate toxin tolerance in long run.
Role of microRNA-21 in hypertrophic cardiac remodeling
Authors: Watanabe Ken , Narumi Taro , Watanabe Tetsu , Otaki Yoichiro , Takahashi Tetsuya , Aono Tomonori , Goto Jun , Toshima Taku , Sugai Takayuki , Wanezaki Masahiro , Kutsuzawa Daisuke , Kato Shigehiko , Tamura Harutoshi , Nishiyama Satoshi , Takahashi Hiroki , Arimoto Takanori , Shishido Tetsuro , Watanabe Masafumi
Published: November 2019

Hypertension is a major public health problem among with aging population worldwide. It causes cardiac remodeling, including hypertrophy and interstitial fibrosis, which leads to development of hypertensive heart disease (HHD). Although microRNA-21 (miR-21) is associated with fibrogenesis in multiple organs, its impact on hypertrophic cardiac remodeling in hypertension is not known. Circulating miR-21 level was higher in patients with HHD than that in the control subjects. It also positively correlated with serum myocardial fibrotic markers. MiR-21 expression levels were significantly upregulated in the mice hearts after angiotensin II (Ang II) infusion or transverse aortic constriction (TAC) compared with control mice. Expression level of programmed cell death 4 (PDCD4), a main target of miR-21, was significantly decreased in Ang II infused mice and TAC mice compared with control mice. Expression levels of transcriptional activator protein 1 (AP-1) and transforming growth factor-β1 (TGF-β1), which were downstream targets of PDCD4, were increased in Ang II infused mice and TAC mice compared with control mice. In vitro, mirVana-miR-21-specific inhibitor attenuated Ang II-induced PDCD4 downregulation and contributed to subsequent deactivation of AP-1/TGF-β1 signaling pathway in neonatal rat cardiomyocytes. Thus, suppression of miR-21 prevents hypertrophic cardiac remodeling by regulating PDCD4, AP-1, and TGF-β1 signaling pathway.
Estrogen receptor β exerts tumor suppressive effects in prostate cancer through repression of androgen receptor activity
Authors: Chaurasiya Surendra , Widmann Scott , Botero Cindy , Lin Chin-Yo , Strom Anders M. , Gustafsson Jan-Åke
Published: November 2019

Estrogen receptor β (ERβ) was first identified in the rodent prostate and is abundantly expressed in human and rodent prostate epithelium, stroma, immune cells and endothelium of the blood vessels. In the prostates of mice with inactivated ERβ, mutant phenotypes include epithelial hyperplasia and increased expression of androgen receptor (AR)-regulated genes, most of which are also upregulated in prostate cancer (PCa). ERβ is expressed in both basal and luminal cells in the prostate while AR is expressed in luminal but not in the basal cell layer which harbors the prostate stem cells. To investigate the mechanisms of action of ERβ and its potential cross-talk with AR, we used RNA-seq to study the effects of estradiol or the synthetic ligand, LY3201, in AR-positive LNCaP PCa cells which had been engineered to express ERβ. Transcriptomic analysis indicated relatively few changes in gene expression with ERβ overexpression, but robust responses following ligand treatments. There is significant overlap of responsive genes between the two ligands, as well as ligand-specific alterations. Gene set analysis of down-regulated genes identified an enrichment of androgen-responsive genes, such as FKBP5, CAMKK2, and TBC1D4. Consistently, AR transcript, protein levels, and transcriptional activity were down-regulated following ERβ activation. In agreement with this, we find that the phosphorylation of the CAMKK2 target, AMPK, was repressed by ligand-activated ERβ. Down-regulation of TBC1D4, a major regulator of glucose uptake in prostate, indicates that ERβ is changing glucose metabolism in the prostate. These findings suggest that ERβ-mediated signaling pathways are involved in the negative regulation of AR expression and activity, thus supporting a tumor suppressive role for ERβ in PCa.
alignparse: A Python package for parsing complex features from high-throughput long-read sequencing
Authors: Crawford Katharine H.D. , Bloom Jesse D.
Published: November 2019

Summary & Purpose

Advances in sequencing technology have made it possible to generate large numbers of long, high-accuracy sequencing reads. For instance, the new PacBio Sequel platform can generate hundreds of thousands of high-quality circular consensus sequences in a single run (Rhoads and F. 2015; Hebert et al. 2018). Good programs exist for aligning these reads for genome assembly (Chaisson and Tesler 2012; Li 2018). However, these long reads can also be used for other purposes, such as sequencing PCR amplicons that contain various features of interest. For instance, PacBio circular consensus sequences have been used to identify the mutations in influenza viruses in single cells (Russell et al. 2019), or to link barcodes to gene mutants in deep mutational scanning (Matreyek et al. 2018). For such applications, the alignment of the sequences to the targets may be fairly trivial, but it is not trivial to then parse specific features of interest (such as mutations, unique molecular identifiers, cell barcodes, and flanking sequences) from these alignments.

Here we describe alignparse, a Python package for parsing complex sets of features from long sequences that map to known targets. Specifically, it allows the user to provide complex target sequences in Genbank format that contain an arbitrary number of user-defined sub-sequence features. It then aligns the sequencing reads to these targets and filters alignments based on whether the user-specified features are present with the desired identities (which can be set to different thresholds for different features). Finally, it parses out the sequences, mutations, and/or accuracy of these features as specified by the user. The flexibility of this package therefore fulfills the need for a tool to extract and analyze complex sets of features in large numbers of long sequencing reads.
A short commentary on indents and edges of β-sheets
Authors: Khare Harshavardhan , Ramakumar Suryanarayanarao
Published: November 2019

β-sheets in proteins are formed by extended polypeptide chains, called β-strands. While there is a general consensus on two types of β-strands, viz. ‘edge strands’ (or ‘edges’) and ‘inner strands’ (or ‘central strands’), the possibility of distinguishing between different regions of inner strands remains less explored. In this paper, we address the portions of inner strands of β-sheets that stick out on either or both sides. We call these portions the ‘indent strands’ or ‘indents’ because they give the typical indented appearance to β-sheets. Similar to the edge strands, the indent strands also have β-bridge partner residues on one side while the other side is still open for backbone hydrogen bonds. Despite this similarity, the indent strands differ from the edge strands in terms of various properties such as β-bulges and amino acid composition due to their localization within β-sheets and therefore within folded proteins to certain extent. The localization of indents and edges within folded proteins seems to govern the strategies deployed to deter unhindered β-sheet propagation through β-strand stacking interactions. Our findings suggest that, edges and indents differ in their strategies to avoid further β-strand stacking. Short length itself is a good strategy to avoid stacking and a majority of indents are two residue or shorter in length. Edge strands on the other hand are overall longer. While long edges are known to use various negative design strategies like β-bulges, prolines, strategically placed charges, inward-pointing charged side chains and loop coverage to avoid further β-strand stacking, long indents seem to favor mechanisms such as enrichment in flexible residues with high solvation potential and depletion in hydrophobic residues in response to their less solvent exposed nature. Such subtle differences between indents and edges could be leveraged for designing novel β-sheet architectures.
Is learning anytime, anywhere a good strategy for success? Identifying successful spatial-temporal patterns of on-the-job and full-time students
Authors: Du Xu , Yang Juan , Shelton Brett , Hung Jui-Long
Published: November 2019

Purpose

Online learning is well-known by its flexibility of learning anytime and anywhere. However, how behavioral patterns tied to learning anytime and anywhere influence learning outcomes are still unknown.

Design/methodology/approach

This study proposed concepts of time and location entropy to depict students’ spatial-temporal patterns. A total of 5,221 students with 1,797,677 logs, including 485 on-the-job students and 4,736 full-time students, were analyzed to depict their spatial-temporal learning patterns, including the relationships between identified patterns and students’ learning performance.

Findings

Analysis results indicate on-the-job students took more advantage of anytime, anywhere than full-time students. Students with a higher tendency for learning anytime and a lower level of learning anywhere were more likely to have better outcomes. Gender did not show consistent findings on students’ spatial-temporal patterns, but partial findings could be supported by evidence in neural science or by cultural and geographical differences.

Research limitations/implications

A more accurate approach for categorizing position and location might be considered. Some findings need more studies for further validation. Finally, future research can consider connections between other well-known performance predictors (such as financial situation, motivation, personality and major) and the type of learning patterns.

Practical implications

The findings gained from this study can help improve the understandings of students’ learning behavioral patterns and design as well as implement better online education programs.

Originality/value

This study proposed concepts of time and location entropy to identify successful spatial-temporal patterns of on-the-job and full-time students.
Examining similarities and differences of citation patterns between monographs and papers: a case in biology and computer science
Authors: Wang Yuzhuo , Zhang Chengzhi
Published: November 2019

Purpose

Citation content in academic papers and academic monographs promotes the knowledge flow among different publications. However, existing citation content analysis (CCA) focuses on academic papers and monographs have not received much research attention. We want to know if monographs are appropriate objects of CCA and whether existing methods of analyzing citation in papers are suitable for citation in monographs. Therefore, this paper aims to learn more about features of cited references and citation content in monographs and compare the characteristic of citation pattern between monographs and papers.

Design/methodology/approach

The authors manually annotate the references and syntactic citation content in academic monographs published by Morgan & Claypool and automatically extracted the references and citation content from academic papers published by Public Library of Science. Five features in two types citation pattern, namely, pattern of cited reference (including year, source and mention frequency of reference) and pattern of citation content (including location, length of citation content) are used to examine similarities and differences between monographs and papers.

Findings

The results indicate that between monographs and papers, differences are shown in location, length of citation content and year, source of reference, whereas frequency of mention of reference is similar.

Originality/value

Previous studies have explored the patter of citation content in academic papers. However, none of the existing literature, as far as the authors know, has considered the citation content in academic monographs and the similarities or differences among academic documents when studying the citation pattern.
Fraud triangle in public procurement: evidence from Indonesia
Authors: Rustiarini Ni Wayan , Sutrisno Sutrisno , Nurkholis Nurkholis , Andayani Wuryan
Published: November 2019

Purpose

This study aims to examine the effects of fraud triangle (pressure, opportunity and rationalization) on individual fraudulent behavior in Indonesian public procurement. Empirical research in this area is relatively sparse.

Design/methodology/approach

Data were collected using laboratory experiments.

Findings

The results revealed that fraudulent behavior is higher when an individual has high pressure and high opportunity. These factors play an important role in determining individual rationalization. Most of participants used “displacing responsibility” to rationalize their actions. This study also demonstrated that negative affect mediates the relationship between fraudulent behavior and rationalization.

Research limitations/implications

First, fraudulent behavior research cannot be separated from social desirability bias. Second, the experiments only involved individual decision-making, not in groups. Finally, this study did not examine the effectiveness of rationalization in reducing negative affect.

Practical implications

Over the years, the government has only focused on the identification of pressure and reduction of opportunities, but ignored individual psychological reasons. Considering that procurement fraud is always increasing, the government must more focus on individual reasons to design an effective prevention and detection system.

Social implications

There are various conflicts of interest in public procurement budgeting. These conflicts can distort resource allocation and causes budget leakage. As a result, the government is incapacitated to achieve social and economic goals of the community.

Originality/value

There is limited research about fraud in public procurement budgeting, especially in developing countries. In addition, the fraud triangle research, which focuses on rationalization is still limited.
China’s poverty alleviation over the last 40 years: successes and challenges
Authors: Liu Mingyue , Feng Xiaolong , Wang Sangui , Qiu Huanguang
Published: November 2019

Over the past 40 years, China has made significant progress towards its poverty alleviation goals. The rural population under the current poverty line has decreased by 739.9 million. China has contributed to more than 70 per cent of world poverty reduction. To better promote the new anti‐poverty strategy and to serve as a reference for poverty alleviation in other developing countries, this paper summarises the main experiences of China’s poverty alleviation over the past 40 years and then discusses the challenges associated with implementing the targeted poverty alleviation policy in the new era. China’s experience with poverty alleviation includes development‐oriented poverty alleviation, improving self‐development capabilities of the poor population, encouraging multiple subjects to participate in poverty alleviation and focusing on innovation and ways to improve poverty alleviation. Although China’s poverty alleviation initiatives have achieved significant successes, there are still several challenges that should be of concern in the coming years, such as the diminishing marginal effect of financial inputs on poverty alleviation, the resulting negative incentives for the poor to improve their internal motivations and the insufficient participation of markets and social forces in poverty alleviation. Given these challenges, this paper provides suggestions for anti‐poverty policies beyond 2020.
Overruling uncertainty about preventative medications: the social organisation of healthcare professionals’ knowledge and practices
Authors: Cupit Caroline , Rankin Janet , Armstrong Natalie , Martin Graham P.
Published: November 2019

In this article, we draw on an institutional ethnographic (IE) study of cardiovascular disease prevention in general practice, exploring the work of healthcare professionals who introduce a discussion of risk and preventative medications into consultations with patients. Our aim is to explicate, using IE's theoretical ontology and analytical tools, how troubling patient experiences in this clinical context are coordinated institutionally. We focus our attention on the social organisation of healthcare professionals’ knowledge and front‐line practices, highlighting the textual processes through which they overrule patients’ concerns and uncertainties about taking preventative medication, such that some patients feel unable to openly discuss their health needs in preventative consultations. We show how healthcare professionals activate knowledge of ‘evidence‐based risk reduction’ to frame patients’ queries as ‘barriers’ to be overcome. Our analysis points not to deficiencies of healthcare professionals who lack the expertise or inclination to adequately ‘share decisions’ with patients, but to the ways in which their work is institutionally orientated towards performance measures which will demonstrate to local and national policymakers that they are tackling the ‘burden of (cardiovascular) disease’.
Reproductive Implications and Management of Congenital Uterine Anomalies
Authors: Akhtar MA , Saravelos SH , Li TC , Jayaprakasan K ,   the Royal College of Obstetricians and Gynaecologists
Published: November 2019

Plain language summary

Congenital uterine anomalies (CUAs) are malformations of the womb that develop during fetal life. When a baby girl is in her mother’s womb, her womb develops as two separate halves from two tubular structures called ‘müllerian ducts’, which fuse together before she is born. Abnormalities that occur during the baby’s development can be variable from complete absence of a womb through to more subtle anomalies, which are classified into specific categories. While conventional ultrasound is good in screening for CUAs, 3D ultrasound is used to confirm a diagnosis. If a complex womb abnormality is suspected, MRI scanning may also be used, with a combination of laparoscopy in which a camera is inserted into the cavity of the abdomen, and hysteroscopy, when the camera is placed in the womb cavity. As there can be a link between CUAs and abnormalities of the kidney and bladder, scans of these organs are also usually requested.

Although CUAs are present at birth, adult women typically do not have any symptoms, although some may experience painful periods. Most cases of CUA do not cause a woman to have difficulty in becoming pregnant and the outcome of pregnancy is good. However, these womb anomalies are often discovered during investigations for infertility or miscarriage. Moreover, depending upon the type and severity of CUA, there may be increased risk of first and second trimester miscarriages, preterm birth, poor growth of the baby in the mother’s womb (fetal growth restriction), pre‐eclampsia and difficult positioning of the baby for birth (fetal malpresentation). Surgical treatment is only recommended to a woman who has had recurrent miscarriages and has a septate uterus, i.e., the womb cavity is divided by a partition. In this case, surgery may improve her chances for a successful pregnancy, although the risks of surgery, especially scarring of the womb should be considered. However, further evidence from randomised controlled trials are required to provide conclusive evidence‐based recommendations for surgical treatment for septate uterus. Surgical treatment for other types of CUAs is not usually recommended as the risks outweigh potential benefits, and evidence for any benefits is lacking. Women with CUAs may be at an increased risk of preterm birth even after surgical treatment for a septate uterus. These women, if suspected to be at an increased risk of preterm birth based on the severity of CUA, should be followed up using an appropriate protocol for preterm birth as outlined in UK Preterm Birth Clinical Network Guidance.1>
A Comparative Study of the Effects of Ultrafiltration Membranes and Storage on Phytochemical and Color Properties of Mulberry Juice
Authors: Li Fuhua , Yan Huiming , Li Weizhou , Zhao Jichun , Ming Jian
Published: November 2019

We investigated the influence of both the clarification by ultrafiltration membranes with 100 or 18 kDa molar weight cut‐off (MWCO) and subsequent storage on phenolic properties and color of mulberry juice (MJ). Results showed that clarification by the ultrafiltration membrane with 100 kDa MWCO elevated levels of total polyphenols (↑11.4%), total monomeric anthocyanins (↑87.7%), phenolic acids and flavonoids (↑10‐64%), thus leading to enhanced antioxidant activity (↑twofolds) and α‐glucosidase inhibitory rate (↑23.3%), as well as redness (↑37.9%), which were sharply decreased in the clarified MJ by the ultrafiltration membrane with 18 kDa MWCO. MJ pretreated by the membrane with 100 kDa MWCO exhibited better storage stability than the other two juices. Hence, the ultrafiltration membrane with 100 kDa MWCO has great potential in juice clarification for purpose of enrichment of phenolic compounds, and enhancement of bioactive activities and storage stability.

Practical Application

Mulberry juice has many health benefits related to phenolic compounds. Clarification is necessary to obtain a bright, clear juice and improves juice taste, thus making a favorable first impression on consumer. Ultrafiltration membrane with 100 kDa MWCO is recommended in mulberry juice processing, since it helps to enrich phenolic compounds, and enhance bioactive activities and sensory quality of mulberry juice.
Influence of Packaging Oxygen Transmission Rate on Physical Characteristics of Frozen Cooked Rice Under Various Freezing Conditions
Authors: Cho Chi Heung , Lee Hyun‐Gyu , Jeong Suyeon , Yoo SeungRan
Published: November 2019

The influence of packaging oxygen transmission rate (OTR; 0, 3,000, 5,000, 7,000, and 20,000 [mL/m2]/day) on cooked rice quality factors, including freezing rate and time, moisture content, color parameters, texture characteristics, and morphology, were evaluated. Cooked rice was frozen at −20 and −80 °C using packaging with different OTRs for 14 days. Freezing rates in packaging with lower OTRs (0, 3,000, and 5,000 [mL/m2]/day) were higher than those in packaging with higher OTRs. The moisture content of cooked rice was the highest in OTR 5,000 packaging under all experimental conditions. Lightness (L*) and total color difference (ΔE) values were the highest in OTR 20,000 packaging, whereas ΔE values were the lowest in OTR 5,000 packaging. Hardness and cohesiveness of frozen cooked rice gradually increased from OTR 0 to 5,000 but decreased from OTR 5,000 to 20,000. Morphology was distinct in all conditions and at all OTRs. Thus, we confirmed that the OTR of packaging influences the physical characteristics of frozen cooked rice. Therefore, packaging OTR should be considered when seeking to improve the quality of frozen cooked rice.

Practical Application

Packaging oxygen transmission rate (OTR) influenced quality characteristics of frozen cooked rice under various freezing conditions. Cooked rice frozen in packaging with lower OTRs (0, 3,000, and 5,000 [mL/m2]/day) showed higher freezing rates, higher moisture content, shorter freezing times, smaller ice crystal formation, homogeneous pore distribution, and lower total color differences (ΔE) than did cooked rice frozen in packaging with higher OTRs (7,000 and 20,000 [mL/m2]/day). Packaging OTR influences frozen cooked rice quality characteristics, and should therefore be carefully considered when designing rice products.
Cocaine and chronic stress exposure produce an additive increase in neuronal activity in the basolateral amygdala
Authors: Munshi Soumyabrata , Rosenkranz J. Amiel , Caccamise Aaron , Wolf Marina E. , Corbett Claire M. , Loweth Jessica A.
Published: November 2019

Cocaine addiction is a chronic, relapsing disorder. Stress and cues related to cocaine are two common relapse triggers. We have recently shown that exposure to repeated restraint stress during early withdrawal accelerates the time‐dependent intensification or “incubation” of cue‐induced cocaine craving that occurs during the first month of withdrawal, although craving ultimately plateaus at the same level observed in controls. These data indicate that chronic stress exposure during early withdrawal may result in increased vulnerability to cue‐induced relapse during this period. Previous studies have shown that chronic stress exposure in drug‐naïve rats increases neuronal activity in the basolateral amygdala (BLA), a region critical for behavioral responses to stress. Given that glutamatergic projections from the BLA to the nucleus accumbens are critical for the incubation of cue‐induced cocaine craving, we hypothesized that cocaine withdrawal and chronic stress exposure produce separate increases that additively increase BLA neuronal activity. To assess this, we conducted in vivo extracellular single‐unit recordings from the BLA of anesthetized adult male rats following cocaine or saline self‐administration (6 h/day for 10 days) and repeated restraint stress or control conditions on withdrawal days (WD) 6‐14. Recordings were conducted from WD15 to WD20. Interestingly, cocaine exposure alone increased the spontaneous firing rate in the BLA to levels observed following chronic stress exposure in drug‐naïve rats. Chronic stress exposure during cocaine withdrawal further increased firing rate. These studies may identify a potential mechanism by which both cocaine and chronic stress exposure drive cue‐induced relapse vulnerability during abstinence.