bluuebunny/crossref_metadata_2025 huggingface dataset:
Pseudoreplication in genomics-scale datasets
Authors: Waples Robin S. , Waples Ryan K. , Ward Eric J.
Published: November 2020

In genomics-scale datasets, loci are closely packed within chromosomes and hence provide correlated information. Averaging across loci as if they were independent creates pseudoreplication, which reduces the effective degrees of freedom (df’) compared to the nominal degrees of freedom,df. This issue has been known for some time, but consequences have not been systematically quantified across the entire genome. Here we measured pseudoreplication (quantified by the ratiodf’/df) for a common metric of genetic differentiation (FST) and a common measure of linkage disequilibrium between pairs of loci (r2). Based on data simulated using models (SLiMandmsprime) that allow efficient forward-in-time and coalescent simulations while precisely controlling population pedigrees, we estimateddf’anddf’/dfby measuring the rate of decline in the variance of meanFSTand meanr2as more loci were used. For both indices,df’increases withNeand genome size, as expected. However, even for largeNeand large genomes,df’for meanr2plateaus after a few thousand loci, and a variance components analysis indicates that the limiting factor is uncertainty associated with sampling individuals rather than genes. Pseudoreplication is less extreme forFST, butdf’/df≤0.01 can occur in datasets using tens of thousands of loci. Commonly-used block-jackknife methods consistently overestimated var(FST), producing very conservative confidence intervals. Predictingdf’based on our modeling results as a function ofNe,L,S, and genome size provides a robust way to quantify precision associated with genomics-scale datasets.
Defining the ultrastructure of the hematopoietic stem cell niche by correlative light and electron microscopy
Authors: Agarwala Sobhika , Kim Keun-Young , Phan Sebastien , Ju Saeyeon , Kong Ye Eun , Castillon Guillaume A. , Bushong Eric A. , Ellisman Mark H. , Tamplin Owen J.
Published: November 2020

The blood system is supported by hematopoietic stem and progenitor cells (HSPCs) found in a specialized microenvironment called the niche. Many different niche cell types support HSPCs, however how they interact and their ultrastructure has been difficult to define. Here we show that single endogenous HSPCs can be tracked by light microscopy, then identified by serial block-face scanning electron microscopy (SBEM) at multiscale levels. Using the zebrafish larval kidney marrow (KM) niche as a model, we followed single fluorescently-labeled HSPCs by light sheet microscopy, then confirmed their exact location in a 3D SBEM dataset. Our approach allowed us to identify dopamine beta-hydroxylase (dbh) positive ganglia cells as a previously uncharacterized functional cell type in the HSPC niche. By integrating multiple imaging modalities, we could resolve the ultrastructure of single rare cells deep in live tissue and define all contacts between an HSPC and its surrounding niche cell types.
Bayesian modeling of skewed X inactivation in genetically diverse mice identifies a novelXceallele associated with copy number changes
Authors: Sun Kathie Y , Oreper Daniel , Schoenrock Sarah A , McMullan Rachel , Giusti-Rodríguez Paola , Zhabotynsky Vasyl , Miller Darla R , Tarantino Lisa M , Villena Fernando Pardo-Manuel de , Valdar William
Published: November 2020

Female mammals are functional mosaics of their parental X-linked gene expression due to X chromosome inactivation (XCI). This process inactivates one copy of the X chromosome in each cell during embryogenesis and that state is maintained clonally through mitosis. In mice, the choice of which parental X chromosome remains active is determined by the X chromosome controlling element (Xce), which has been mapped to a 176 kb candidate interval. A series of functionalXcealleles has been characterized or inferred for classical inbred strains based on biased, or skewed, inactivation of the parental X chromosomes in crosses between strains. To further explore the function-structure basis and location of theXce, we measured allele-specific expression of X-linked genes in a large population of F1 females generated from Collaborative Cross strains. Using published sequence data and applying a Bayesian “Pólya urn” model of XCI skew, we report two major findings. First, inter-individual variability in XCI suggests mouse epiblasts contain on average 20-30 cells contributing to brain. Second, NOD/ShiLtJ has a novel and unique functional allele,Xcef, that is the weakest in theXceallelic series. Despite phylogenetic analysis confirming that NOD/ShiLtJ carries a haplotype almost identical to the well-characterized C57BL/6J (Xceb), we observed unexpected patterns of XCI skewing in females carrying the NOD/ShiLtJ haplotype within theXce. Copy number variation is common at theXcelocus and we conclude that the observed allelic series is a product of independent and recurring duplications shared between weakXcealleles.
Contemplative mental training reduces hair glucocorticoid levels in a randomized clinical trial
Authors: Puhlmann Lara M.C. , Vrtička Pascal , Linz Roman , Stalder Tobias , Kirschbaum Clemens , Engert Veronika , Singer Tania
Published: November 2020

Objective

This study had the objective to investigate the effect of regular contemplative mental training on endocrine indices of long-term stress.

Methods

An open-label efficacy trial comprising three distinct 3-month modules targeting attention and interoception, socio-affective or socio-cognitive abilities through dyadic exercises and secularised meditation practices was designed and carried out in 332 healthy meditation-naive adults. Participants underwent the training for up to 9 months or were assigned to a retest control cohort. Chronic stress indices were assayed at four timepoints, i.e., pre-training and following each module. The main outcome measures were cortisol and cortisone concentration in hair and self-reported chronic stress

Results

N=362 initial individuals were randomized, of whom n=30 dropped out before study initiation, n=4 before first sampling and n=2 were excluded. N=99 participants did not provide hair samples. Data from three separate training cohorts revealed consistent decreases in hair cortisol and cortisone levels over the training period. This effect increased with practice frequency, was independent of training content and not associated with change in self-reported chronic stress.

Conclusions

Our results point to the reduction of long-term cortisol exposure as a mechanism via which contemplative mental training may exert positive effects on practitioners’ health.

Trial registration

ClinicalTrials.gov identifier:NCT01833104
Brief Report: The Virucidal Efficacy of Oral Rinse Components Against SARS-CoV-2 In Vitro
Authors: Statkute Evelina , Rubina Anzelika , O’Donnell Valerie B , Thomas David W. , Stanton Richard J.
Published: November 2020

The ability of widely-available mouthwashes to inactivate SARS-CoV-2 in vitro was tested using a protocol capable of detecting a 5-log10 reduction in infectivity, under conditions mimicking the naso/oropharynx. During a 30 second exposure, two rinses containing cetylpyridinium-chloride and a third with ethanol/ethyl lauroyl arginate eliminated live virus to EN14476 standards (>4-log10 reduction), while others with ethanol/essential oils and povidone-iodine (PVP-I) eliminated virus by 2-3-log10. Chlorhexidine or ethanol alone displayed little or no ability to inactivate virus. Studies are warranted to determine whether these formulations can inactivate virus in the human oropharynxin vivo, and whether this might impact transmission risk.
In VitroActivity of Itraconazole Against SARS-CoV-2
Authors: Van Damme Ellen , De Meyer Sandra , Bojkova Denisa , Ciesek Sandra , Cinatl Jindrich , De Jonghe Steven , Jochmans Dirk , Leyssen Pieter , Buyck Christophe , Neyts Johan , Van Loock Marnix
Published: November 2020

Background

As long as there is no vaccine available, having access to inhibitors of SARS-CoV-2 will be of utmost importance. Antivirals against coronaviruses do not exist, hence global drug re-purposing efforts have been carried out to identify agents that may provide clinical benefit to patients with COVID-19. Itraconazole, an antifungal agent, has been reported to have potential activity against animal coronaviruses.

Methods

Using cell-based phenotypic assays, thein vitroantiviral activity of itraconazole and 17-OH itraconazole was assessed against clinical isolates from a German and Belgian patient infected with SARS-CoV-2.

Results

Itraconazole demonstrated antiviral activity in human Caco-2 cells (EC50= 2.3 μM; MTT assay). Similarly, its primary metabolite, 17-OH itraconazole, showed inhibition of SARS-CoV-2 activity (EC50= 3.6 μM). Remdesivir inhibited viral replication with an EC50= 0.4 μM. Itraconazole and 17-OH itraconazole resulted in a viral yield reductionin vitroof approximately 2-log10and approximately 1-log10, as measured in both Caco-2 cells and VeroE6-eGFP cells, respectively. The viral yield reduction brought about by remdesivir or GS-441524 (parent nucleoside of the antiviral prodrug remdesivir; positive control) was more pronounced, with an approximately 3 log10drop and >4 log10drop in Caco-2 cells and VeroE6-eGFP cells, respectively.

Discussion

Itraconazole and 17-OH itraconazole exertin vitrolow micromolar activity against SARS-CoV-2. Despite thein vitroantiviral activity, itraconazole did not result in a beneficial effect in hospitalized COVID-19 patients in a clinical study (EudraCT Number: 2020-001243-15).

Highlights

Itraconazole exertedin vitrolow micromolar activity against SARS-CoV-2 (EC50= 2.3 μM)

Remdesivir demonstrated potent antiviral activity, confirming validity of the assay

Itraconazole has since shown no efficacy in a clinical study in hospitalized COVID-19 patients
Conserved prolines in the coiled coil-OB domain linkers of proteasomal ATPases facilitate eukaryotic proteasome base assembly
Authors: Cheng Chin Leng , Wong Michael K , Li Yanjie , Hochstrasser Mark
Published: November 2020

The proteasome is a large protease complex that degrades both misfolded and regulatory proteins. In eukaryotes, the 26S proteasome contains six different AAA+ ATPase subunits, Rpt1-Rpt6, which form a hexameric ring as part of the base subcomplex that drives unfolding and translocation of substrates into the proteasome core. Archaeal proteasomes contain only a single type of ATPase subunit, the proteasome-activating nucleotidase (PAN), which forms a trimer-of-dimers and is homologous to the eukaryotic Rpt subunits. A key PAN proline residue (P91) formscisandtranspeptide bonds in successive subunits around the ring, allowing efficient dimerization through upstream coiled coils. The importance of the equivalent Rpt prolines in eukaryotic proteasome assembly was unknown. We show an equivalent proline is strictly conserved in Rpt3 (inS. cerevisiae, P93) and Rpt5 (P76), well conserved in Rpt2 (P103), and loosely conserved in Rpt1 (P96) in deeply divergent eukaryotes, but in no case is its mutation strongly deleterious to yeast growth. However, therpt2-P103A,rpt3-P93A, andrpt5-P76Amutations all cause synthetic defects with specific base assembly chaperone deletions. The Rpt5-P76A mutation decreases the levels of the protein and induces a mild proteasome assembly defect. The yeastrpt2-P103A rpt5-P76Adouble mutant has strong growth defects attributable to defects in proteasome base formation. Several Rpt subunits in this mutant form aggregates that are cleared, at least in part, by the Hsp42-mediated protein quality control (PQC) machinery. We propose that the conserved Rpt linker prolines promote efficient 26S proteasome base assembly by facilitating specific ATPase heterodimerization.
Keeping weight off: Mindfulness-Based Stress Reduction alters amygdala functional connectivity during weight loss maintenance in a randomized control trial
Authors: Chumachenko Serhiy Y. , Cali Ryan , Rosal Milagros C. , Allison Jeroan , Person Sharina , Ziedonis Douglas , Nephew Benjamin C. , Moore Constance M. , Zhang Nanyin , King Jean A. , Fulwiler Carl
Published: November 2020

Obesity is associated with significant comorbidities and financial costs. While behavioral interventions produce clinically meaningful weight loss, weight loss maintenance is challenging. The objective was to improve understanding of the neural and psychological mechanisms modified by mindfulness that may predict clinical outcomes.

Individuals who intentionally recently lost weight were randomized to Mindfulness-Based Stress Reduction (MBSR) or a control healthy living course. Anthropometric and psychological factors were measured at baseline, 8 weeks and 6 months. Functional connectivity (FC) analysis was performed at baseline and 8 weeks to examine FC changes between regions of interest selected a priori, and independent components identified by independent component analysis. The association of pre-post FC changes with 6-month weight and psychometric outcomes was then analyzed.

Significant group x time interaction was found for FC between the amygdala and ventromedial prefrontal cortex, such that FC increased in the MBSR group and decreased in controls. Non-significant changes in weight were observed at 6 months, where the mindfulness group maintained their weight while the controls showed a weight increase of 3.4% in BMI. Change in FC at 8-weeks between ventromedial prefrontal cortex and several ROIs was associated with change in depression symptoms but not weight at 6 months. This pilot study provides preliminary evidence of neural mechanisms that may be involved in MBSR’s impact on weight loss maintenance that may be useful for designing future clinical trials and mechanistic studies.
Immune memory in mild COVID-19 patients and unexposed donors from India reveals persistent T cell responses after SARS-CoV-2 infection
Authors: Ansari Asgar , Arya Rakesh , Sachan Shilpa , Jha Someshwar Nath , Kalia Anurag , Lall Anupam , Sette Alessandro , Grifoni Alba , Weiskopf Daniela , Coshic Poonam , Sharma Ashok , Gupta Nimesh
Published: November 2020

Understanding the causes of the diverse outcome of COVID-19 pandemic in different geographical locations is important for the worldwide vaccine implementation and pandemic control responses. We analyzed 42 unexposed healthy donors and 28 mild COVID-19 subjects up to 5 months from the recovery for SARS-CoV-2 specific immunological memory. Using HLA class II predicted peptide megapools, we identified SARS-CoV-2 cross-reactive CD4+ T cells in around 66% of the unexposed individuals. Moreover, we found detectable immune memory in mild COVID-19 patients several months after recovery in the crucial arms of protective adaptive immunity; CD4+ T cells and B cells, with a minimal contribution from CD8+ T cells. Interestingly, the persistent immune memory in COVID-19 patients is predominantly targeted towards the Spike glycoprotein of the SARS-CoV-2. This study provides the evidence of both high magnitude pre-existing and persistent immune memory in Indian population. By providing the knowledge on cellular immune responses to SARS-CoV-2, our work has implication for the development and implementation of vaccines against COVID-19.
Perphenazine-macrocycle conjugates rapidly sequester the Aβ42 monomer and inhibit amyloid formation
Authors: Ball Sarah R. , Adamson Julius S. P , Sullivan Michael A. , Zimmermann Manuela R. , Lo Victor , Sanz-Hernandez Maximo , Jiang Frank , Kwan Ann H. , Werry Eryn L. , Knowles Tuomas P. J. , Kassiou Michael , Meisl Georg , Todd Matthew H. , Rutledge Peter J. , Sunde Margaret
Published: November 2020

Alzheimer’s disease is imposing a growing social and economic burden worldwide and effective therapies are required. Strategies aimed at the removal of fibrillar plaques formed by the amyloid-β peptide have not proved therapeutic and the focus has shifted to approaches that target the cytotoxic oligomeric amyloid-β species that are populated before fibrils are deposited. We have designed and synthesized perphenazine-cyclam conjugates that specifically and rapidly bind to the monomeric form of Aβ42, reducing the production of both cytotoxic oligomers and amyloid fibrils. We have applied detailed kinetic analysis and NMR spectroscopy to show that the perphenazine-cyclam conjugates divert the Aβ42 monomer into amorphous aggregates that are not toxic to differentiated SH-SY5Y cellsin vitro. Unlike most other amyloid inhibitors studied to date, these conjugates inhibit oligomer and fibril assembly even in the presence of pre-formed fibrillar seeds, demonstrating that they act through a monomer sequestration mechanism. These modular, three-dimensional conjugates therefore effectively prevent monomer-dependent secondary nucleation, the autocatalytic process that generates the majority of toxic oligomers.
A novel Fis1 inhibiting peptide reverses diabetic endothelial dysfunction in human resistance arteries
Authors: Nolden Kelsey A. , Kakarla Mamatha , Egner John M. , Wang Jingli , Harwig Megan C. , Puppala Venkata K. , Hofeld Benjamin C. , Arnold Leggy A. , Trykall David Z. , Peterson Francis C. , Roberts Michelle L. , Jenson David M. , Hill R. Blake , Widlansky Michael E.
Published: November 2020

Mitochondrial dysfunction is one of several factors that drive development of vascular endothelial dysfunction in type 2 diabetes (T2DM). In endothelial cells from T2DM patients, mitochondrial networks are highly fragmentated with increased expression of mitochondrial fission protein 1 (Fis1). However, whether manipulation of Fis1 expression and activity in endothelial vessels from T2DM patients alters endothelial function remains unknown. Here, molecular suppression of Fis1 reversed impaired endothelium-dependent vasodilation of vessels from T2DM patients, as well as healthy human vessels exposed to high (33 mM) or low (2.5 mM) glucose, while preserving NO bioavailability and improving endothelial cell layer integrity. Conversely, overexpression of Fis1 in healthy vessels impaired vasodilation and increased mitochondrial superoxide, suggesting a causative role. Application of a novel and specific Fis1 inhibitor, pep213, improved endothelium-dependent vasodilation of vessels from T2DM patients, as well as healthy vessels exposed to high glucose or Fis1 overexpression, by improving NO bioavailability and decreasing excess mitochondrial ROS generation. The specificity of pep213 was determined through multiple biophysical techniques and a 1.85 Å crystal structure of pep213 in complex with Fis1. These data support that excessive mitochondrial fragmentation drives endothelial vessel dysfunction and supports a potential novel therapeutic route for treating diabetic microvascular disease through pharmacological inhibition of Fis1.
Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells
Authors: Pae Juhee , Ersching Jonatan , Castro Tiago B. R. , Schips Marta , Mesin Luka , Allon Samuel J. , Ordovas-Montanes Jose , Mlynarczyk Coraline , Melnick Ari , Efeyan Alejo , Shalek Alex K. , Meyer-Hermann Michael , Victora Gabriel D.
Published: November 2020

During affinity maturation, germinal center (GC) B cells alternate between proliferation and so-matic hypermutation in the dark zone (DZ) and affinity-dependent selection in the light zone (LZ). This anatomical segregation imposes that the vigorous proliferation that allows clonal expansion of positively-selected GC B cells takes place ostensibly in the absence of the signals that triggered selection in the LZ, as if by “inertia.” We find that such inertial cycles specifically require the cell cycle regulator cyclin D3. Cyclin D3 dose-dependently controls the extent to which B cells proliferate in the DZ and is essential for effective clonal expansion of GC B cells in response to strong T follicular helper (Tfh) cell help. Introduction into theCcnd3gene of a Burkitt lymphoma-associated gain-of-function mutation (T283A) leads to larger GCs with increased DZ proliferation and, in older mice, to clonal B cell lymphoproliferation, suggesting that the DZ inertial cell cycle program can be coopted by B cells undergoing malignant transformation.
Microbiomes attached to fresh perennial ryegrass- are temporally resilient and adapt to changing ecological niches
Authors: Huws Sharon A. , Edwards Joan. E. , Lin Wanchang , Rubino Francesco , Alston Mark , Swarbreck David , Caim Shabhonam , Stevens Pauline Rees , Pachebat Justin , Won Mi-Young , Oyama Linda B. , Creevey Christopher J. , Kingston-Smith Alison H.
Published: November 2020

Gut microbiomes, such as the rumen, greatly influence host nutrition due to their feed energy-harvesting capacity. We investigated temporal ecological interactions facilitating energy-harvesting at the fresh perennial ryegrass (PRG)-biofilm interface in the rumen using anin saccoapproach and prokaryotic metatranscriptomic profiling. Network analysis identified two distinct sub-microbiomes primarily representing primary (≤4h) and secondary (≥4h) colonisation phases and the most transcriptionally active bacterial families (i.eFibrobacteriaceae, SelemondaceaeandMethanobacteriaceae) did not interact with either sub-microbiome, indicating non-cooperative behaviour. Conversely,Prevotellaceaehad most transcriptional activity within the primary sub-microbiome (focussed on protein metabolism) andLachnospiraceaewithin the secondary sub-microbiome (focussed on carbohydrate degradation). Putative keystone taxa, with low transcriptional activity, were identified within both sub-microbiomes, highlighting the important synergistic role of minor bacterial families, however, we hypothesise that they may be ‘cheating’ in order to capitalise on the energy-harvesting capacity of other microbes. In terms of chemical cues underlying transition from primary to secondary colonisation phases, we suggest that AI-2 based quorum sensing plays a role, based on LuxS gene expression data, coupled with changes in PRG chemistry. In summary, this study provides the first major insight into the complex temporal ecological interactions occurring at the plant-biofilm interface within the rumen.
Immunoproteasome deficiency leads to sustained pancreatic injury and delayed recovery from experimental pancreatitis
Authors: De Freitas Chama Laura L. , Ebstein Frédéric , Wiesrecker Birthe , Wagh Preshit R. , Weiss Frank U. , Junker Heike , Studencka-Turski Maja , Lerch Markus M. , Krüger Elke , Sendler Matthias
Published: November 2020

Background & Aims

Uncovering potential new targets involved in pancreas recovery may permit the development of new therapies and improvement of pancreatitis treatment. One disease mechanism comprises the endoplasmic reticulum stress response and a key regulator to prevent proteotoxic stress in an inflammatory context is the immunoproteasome, an induced form of the constitutive proteasome. Our aim was therefore to investigate the role of the immunoproteasome in acute pancreatitis.

Methods

Acute pancreatitis was induced in wild type and LMP7−/−mice and several biochemical parameters for disease severity were addressed, including protease activities and histology of pancreatic damage. Real-time PCR was used to measure pro-inflammation and unfolded protein response. Serum IL-6 was detected by cytometric bead assay. Western blotting was used to quantify the ratio of ubiquitin-protein conjugates as well as unfolded protein response activation. Immunofluorescence identified leukocytes infiltration as well as ubiquitin-protein conjugates in the pancreas.

Results

In this study, we demonstrate that the β5i/LMP7-subunit deletion correlates with persistent pancreatic damage. Interestingly, immunoproteasome-deficient mice unveil increased activity of pancreatic enzymes as well as higher secretion of Interleukin-6 and transcript expression of the Interleukin IL-1β, IFN-β cytokines and the CXCL-10 chemokine. Thereafter, acinar cell death was increased, which appears to be due to the greater accumulation of ubiquitin-protein conjugates and prolonged unfolded protein response.

Conclusions

Our findings suggest that the immunoproteasome plays a protective role in acute pancreatitis via its role in the clearance of damaged proteins and the balance of ER-stress responses in pancreatic acini as well as in macrophages cytokine production.
Revealing interspecies transmission barriers of avian influenza A viruses
Authors: Naguib Mahmoud M. , Eriksson Per , Jax Elinor , Nilsson Jonas , Sihlbom Carina , Lindskog Cecilia , Bröjer Caroline , Olsson Britt-Marie , Wille Michelle , Waldenström Jonas , Larson Göran , Kraus Robert H. S. , Lundkvist Åke , Olsen Björn , Järhult Josef D. , Ellström Patrik
Published: November 2020

Influenza A virus (IAV) pandemics result from interspecies transmission events within the avian reservoir and further to mammals including humans. Investigating molecular virus–host interactions dictating this process and the adaptations to the new hosts that follow is vital to understand zoonotic IAV spread. Receptor incompatibility has been suggested to limit zoonotic IAV transmission from the wild bird reservoir. Other barriers to interspecies transmission, particularly within the avian system, largely remain elusive. Through assessment of infection dynamics of mallard origin IAV in two different avian hosts, coupled with studies of receptor expression and host response we aimed to reveal the host-pathogen interactions in a cross-species transmission event. We found that shedding patterns and innate immune responses were highly dependent on viral genotypes, host species and inoculation routes, but less dependent on receptor expression. Further, in contrary to the prevailing dogma we demonstrate that birds can produce a wide range of different sialylated structures also found in mammals, e.g. extendedN-andO-linked Neu5Acα2,6 terminated glycans. Overall, receptor incompatibility is not the sole transmission barrier for IAV between birds and to humans, but other host-pathogen factors deserve dedicated studies to achieve proper pandemic preparedness.
Dynamical Systems Approach to Evolution-Development Congruence: Revisiting Haeckel’s Recapitulation Theory
Authors: Kohsokabe Takahiro , Kaneko Kunihiko
Published: November 2020

It is acknowledged that embryonic development has tendency to proceed from common toward specific. Ernst Haeckel raised the question of why that tendency prevailed through evolution, and the question remains unsolved. Here, we revisit Haeckel’s recapitulation theory, i.e., the parallelism between evolution and development through numerical evolution and dynamical systems theory. By using intracellular gene-expression dynamics with cell-to-cell interaction over spatially aligned cells to represent the developmental process, gene regulation networks (GRN) that govern these dynamics evolve under the selection pressure to achieve a prescribed spatial gene expression pattern. For most numerical evolutionary experiments, the evolutionary pattern changes over generations, as well as the developmental pattern changes governed by the evolved GRN exhibit remarkable similarity. Both pattern changes consisted of several epochs where stripes are formed in a short time, whereas for other temporal regimes, pattern hardly changes. In evolution, these quasi-stationary generations are needed to achieve relevant mutations, whereas in development, they are due to some gene expressions that vary slowly and control the pattern change. These successive epochal changes in development and evolution are represented as common bifurcations in dynamical systems theory, regulating working network structure from feedforward subnetwork to those containing feedback loops. The congruence is the correspondence between successive acquisition of subnetworks through evolution and changes in working subnetworks in development. Consistency of the theory with the segmentation gene-expression dynamics is discussed. Novel outlook on recapitulation and heterochrony are provided, testable experimentally by the transcriptome and network analysis.
Identifying chromosomal subpopulations based on their recombination histories advances the study of the genetic basis of phenotypic traits
Authors: Ruiz-Arenas Carlos , Cáceres Alejandro , López Marcos , Pelegrí-Sisó Dolors , González Josefa , González Juan R.
Published: November 2020

Recombination is a main source of genetic variability. However, the potential role of the variation generated by recombination in phenotypic traits, including diseases, remains unexplored because there is currently no method to infer chromosomal subpopulations based on recombination pattern differences. We developed recombClust, a method that uses SNP-phased data to detect differences in historic recombination in a chromosome population. We validated our method by performing simulations and by using real data to accurately predict the alleles of well-known recombination modifiers, including common inversions in Drosophila melanogaster and human, and the chromosomes under selective pressure at the lactase locus in humans. We then applied recombClust to the complex human 1q21.1 region, where nonallelic homologous recombination produces deleterious phenotypes. We discovered and validated the presence of two different recombination histories in these regions that significantly associated with the differential expression of ANKRD35 in whole blood and that were in high linkage with variants previously associated with hypertension. By detecting differences in historic recombination, our method opens a way to assess the influence of recombination variation in phenotypic traits.
Mohan Dixit
Authors: Gupta Vishal , Premapuri Priyanka
Published: November 2020

Mohan Dixit, Head, Sales and Marketing, India Operations, EuroMotoCorp Pvt. Ltd., an automobile manufacturing multinational company headquartered in Munich, Germany. This case outlines the harried nature of his life: professional problems (decrease in the market share, not being able to say ‘no’, unable to delegate, pressed for time, member of too many committees) and personal issues (weight gain, not able to spend time for his personal interests) and family problems (work-life balance issue). The case can be taught through different angles, including individual behaviour, transaction analysis, time and stress management, career management and general management. Apart from this, the case discusses the emotional instability of Dixit and the automatic cycle of behavior of Dixit in various situations and events. The case also discusses the ‘ego-self’ and the ‘natural—self’ of a person and how the two should be balanced for a good quality of life. The case thus delves deep into the psychology of a person and discusses how his/her thoughts or inner talk should be managed for a content and successful personal and professional life.
Nucor Rochelle India Limited (NRIL)
Authors: Vohra Neharika , Narain Arohini , Bhatnagar Deepti
Published: November 2020

The case describes how a leader simultaneously addresses various aspects of business and people management to achieve a turnaround. The actions taken by the leader to get rid of the non-functional practices, nurture the existing practices, and create new strategies and processes to accomplish business growth are described. The leader reshapes the organisational culture in partnership with the human resource department. The case can be used to show the different leadership styles (transactional and transformational) and tactics for managing change-partnering with HR to revamp people practices, cherry-pick and develop the right talent, etc.
Mr. Mehta's Dilemma: A Case of Performance Appraisal Politics
Authors: Chandwani Rajesh , Varkkey Biju
Published: November 2020

The case describes the dilemma of Mr Mehta, Regional Head HR of AXZ, a large IT company in India. Mr Mehta had received an appeal from an employee Mr Rajesh Kumar who alleged that he was wrongly appraised by his manager Mr Yogesh Desai. Both Desai and Kumar have presented their perspectives to Mr Mehta. While Mr Mehta understands Mr Desai's challenges in performance appraisal process, he also is concerned about Rajesh, who is a talented employee with rare skill sets. Apart from the case specific issues related to the two employees, Mr Mehta is also concerned about the problems arising from the current performance appraisal system, especially after AXZ acquired UTVC, which had a very different performance appraisal system. The case also provides an opportunity to discuss the challenges associated with bell curve implementation and discrimination in performance appraisal processes in organizations.
Dr. Narendran's Dilemma
Authors: Chand Vijaya Sherry
Published: November 2020

Dr. Narendran, Director, Indian Medicine (Siddha) College, has been requested by the Head of the College's Pharmacology Department to ensure intellectual protection for, and commercialisation of, a formulation that he had developed for coronary atherosclerosis. Such a request has been made for the first time in the College, and the Director has to decide how it fits into the educational and research mandate of the College. He also has with him a brief market study of the formulation's potential.
Directorate of Education, Delhi
Authors: Sharma Rajeev , Dixit M. R. , Verma Sanjay
Published: November 2020

The case describes changes brought about in academic and administrative aspects of the Directorate of Education, Delhi, after Ms. Rina Ray, a new secretary of education, took over. When she joined office, the overall enrolment in government schools, numbering more than 900, had been declining and less than 50% of children were passing in class X board examination. Within a period of four years, enrolment in government schools and pass percentage of children increased, and children and teachers gained recognition in sports and co-curricular activities. This was made possible by several mechanisms to facilitate and monitor performance of administrative and academic staff, by adopting information technology at all levels to facilitate administration, and improve teaching learning.
An improved model for performances calculation in spoke-type permanent-magnet machines considering magnetization orientation and finite soft-magnetic material permeability
Authors: Jabbari Ali , Dubas Frédéric
Published: November 2020

Purpose

In semi-analytical modeling of spoke-type permanent-magnet (PM) machines (STPMM), the saturation effect is usually neglected (i.e. iron parts are considered to be infinitely permeable) and the PM magnetization is assumed tangential (i.e. magnetization pattern is considered to be tangential-parallel). This paper aims to present an improved two-dimensional (2D) subdomain technique for STPMM with the PM magnetization orientation in quasi-Cartesian coordinates by using hyperbolic functions considering non-homogeneous Neumann boundary conditions (BCs) in non-periodic regions and by applying the interfaces conditions (ICs) in both directions (i.e. t- and θ edges ICs).

Design/methodology/approach

The polar coordinate system is transformed into a quasi-Cartesian coordinate system. The rotor and stator regions are divided into primary subdomains, and a partial differential equation (PDE) is assigned to each subdomain. In the PM region, the magnetization orientation is considered in the equations. By applying BCs, the general solution of the equations is determined, and by applying the ICs, the corresponding coefficients are determined.

Findings

Using the proposed coordinate system, the general solution of PDEs and their coefficients can mathematically be simplified. The magnetic field and non-intrinsic unbalanced magnetic forces (UMF) calculations have been performed for three different values of iron core relative permeability (200, 800 and ∞), as well as different magnetization orientation values (135 and 80 degrees). The semi-analytical model based on the subdomain technique is compared with those obtained by the 2D finite-element analysis (FEA). Results disclose that the PM magnetization angle can affect directly the performance characteristics of the STPMM.

Originality/value

A new model for prediction of electromagnetic performances in the STPMM takes into account magnetization direction, and soft magnetic material relative permeability in a pseudo-Cartesian coordinate system by using subdomain technique is presented.
Job crafting, workplace civility and work outcomes: the mediating role of work engagement
Authors: Gupta Anuj , Singh Pankaj
Published: November 2020

Purpose

The antecedents and consequences of work engagement have been extensively discussed and analyzed in the previous literature; however, identifying cost-effective measures that can sustain work engagement to boost work outcomes has received sparse attention in the Indian information technology (IT) context. This study aims to provide new insights concerning the associations of job crafting and workplace civility with work engagement and its corresponding outcomes, such as change perception, general life satisfaction and intention to quit.

Design/methodology/approach

Hypotheses were tested using structural equation modeling on data obtained from 369 software developers in India using questionnaire surveys.

Findings

Results confirmed that work engagement partially mediated the association of job crafting and workplace civility with the perception of change and general life satisfaction. The negative associations of job crafting and workplace civility with the intention to quit were also partially mediated by work engagement. The findings can be used to inform human resources strategies to boost work engagement and subsequent work outcomes.

Research limitations/implications

The results of this empirical work will offer insights to managers who are looking for cost-effective interventions and behaviors aimed at increasing work engagement and, consequently, achieving effective work outcomes.

Originality/value

This study contributes by empirically testing the application of novel employee-driven practices in improving work engagement and work outcomes, particularly in the context of IT companies in India.
Stacked value streams of hybrid energy storage systems in prosumer microgrids
Authors: Gbadegesin Azizat Olusola , Sun Yanxia , Nwulu Nnamdi I.
Published: November 2020

Purpose

Storage systems are deemed to be unable to provide revenue commensurate with the resources invested in them, thus discouraging their incorporation within power networks. In prosumer microgrids, storage systems can provide revenue from reduced grid consumption, energy arbitraging or when serving as back-up power. This study aims to examine stacking these revenue streams with the aim of making storage systems financially viable for inclusion in prosumer microgrids.

Design/methodology/approach

With the aim of reducing self-consumption and maximising revenue, the prosumer microgrid incorporating hybrid energy storage systems (HESS) and solar PV power is solved using the CPLEX solver of the Advanced Interactive Multidimensional Modeling Software (AIMMS). The financial analysis of the results is carried out to provide the payback periods of different system configurations of the prosumer microgrid.

Findings

The findings reveal that the payback period of the three HESS when minimising grid expenses during self-consumption alone and when compared with stacked revenue streams shows an improvement from 4.8–11.2 years to 2.4–6.6 years. With stacked HESS revenues, the supercapacitor-lithium ion battery HESS gave the shortest payback period of 2.31 years when solar PV power is at 75% penetration level.

Originality/value

Existing literature has considered revenue streams of storage systems at the electrical power transmission and distribution levels, but not for prosumer microgrids in particular. This study has captured these benefits and verified the profitability of stacking revenue from HESS to prosumer microgrids, using a case study.
Understanding organizational change management: the role of micro and macro influences
Authors: Harden Erika , Ford Lucy R. , Pattie Marshall , Lanier Patricia
Published: November 2020

Purpose

In response to external conditions, organizations yearn to gain a competitive edge during unremitting change. Recognizing the importance of managing change, researchers have aggressively investigated organizational change at the macro level. This research, however, argues that an employee's ability to cope with change is a function of both micro (individual) and macro (contextual) factors.

Design/methodology/approach

The survey data were collected at an organization that was undergoing a significant internal change. Correlational and structural equation modeling techniques were used for data analysis.

Findings

The results suggest that individual differences (intolerance for ambiguity) and contextual factors (LMX, TMX receipts and TMX contributions) are important factors for understanding the ability to manage organizational change effectively. Additionally, it is argued that contextual factors not only have direct effects on coping with change but indirect effects through perceptions of work group effectiveness. Our results indicate that both micro and macro factors are important for understanding the ability to cope with and manage change.

Research limitations/implications

The research leaves open some interesting questions around the role of contextual factors in coping with change, in addition to the interaction with individual differences.

Practical implications

Most sources discuss change as focused at the organizational level. Managers will be well served to understand that the degree to which employees cope effectively with change will be partly determined by the interaction of individual differences and the organizational and team level context.

Originality/value

This research extends our understanding of the relationship between social exchange relationships and how individuals cope with change in organizations and the mechanism by which that occurs.
The radical ambitions of counter‐radicalization
Authors: Martin Thomas
Published: November 2020

The “Trojan Horse” scandal laid bare an anxiety at the heart of the British security establishment; an anxiety that brings together questions of identity, values, and security within the demand to manage radicalization. It is an anxiety that, I will argue, reveals a novel conceptualization of threat that has driven the UK’s security and communities policies within the “war on terror.” This conceptualization emerges within Prevent, the UK’s counter‐radicalization strategy. Yet, I argue, the extensive literature on Prevent has failed to adequately articulate this underlying, core logic. To date, the Prevent literature has effectively demonstrated the ways in which Muslim communities in the United Kingdom have been policed through British counter‐radicalization policy. Yet, this analysis struggles to explain the expansion of Prevent into a wider range of “extremist” spaces. In this article, I contend that it is more useful to situate Prevent as a particular conception of power; a logic and an analysis of threat that demands new forms of government intervention. To do so, this article provides a genealogical reading of Prevent, locating it as a radical extension of state security ambitions to intervene early, making explicit a vision of security in which life as a process of becoming is produced as an object of management. The paper draws out the ramifications of this analysis to think through fundamental shifts in the principles and practices of contemporary security aspirations.
Redistribution and progressivity of the Italian personal income tax, 40 years later
Authors: Baldini Massimo
Published: November 2020

The structure of the Italian personal income tax has undergone several important changes since its introduction in 1974, following a path similar to those in other advanced economies. These modifications have affected its redistributive impact in ways that a priori are not easily identifiable, since they have often moved in divergent directions. The aim of this paper is to study how the redistributive effect (i.e. the ability of the tax to reduce inequality in post‐tax incomes) and progressivity (i.e. the rate at which tax incidence increases with income) of the tax have changed, comparing its structure at the end of the 1970s with its current version. Contrary to what might be expected from the reduction in top marginal tax rates, after 40 years the Italian personal income tax is more redistributive and slightly more globally progressive. A simple decomposition enables one to appreciate the importance that policy choices, inflation and the evolution of income distribution have had in shaping its effects over time. The lack of automatic adjustment mechanisms to inflation has produced a strong monetary fiscal drag effect, dampening the progressivity of the tax and increasing its burden. Policy changes, however, managed to make the tax more redistributive, and not less progressive. Compared with 40 years ago, the incidence of the tax has decreased on lower incomes, while increasing on middle and high incomes.
Relationship of living historical memories and news source with national identity: A latent class analysis
Authors: Li Manyu , Lin Hanzhang , Maer Maria Natalia Damayanti
Published: November 2020

Previous research has suggested that national identity is associated with one’s memory of the nation’s past (i.e., historical events) and current information received from mass media. This study tied these two areas of research to examine if narratives of historical memory, the valence of those memories, and preferred media use/news sources (traditional vs. digital) would be associated with national identity, trust in government, and system justification. Data were obtained through the Digital Influence II Survey–Hong Kong region. Participants were asked to recall three historical events that had the greatest impact on their country and to report the valence of their evaluation of those events. Using latent class analysis, a two‐class structure (superordinate group focus vs. subgroup focus memory) was identified from participants’ historical narratives. For participants in the superordinate group focus, valence on the historical memories was positively associated with trust in government, system justification, and national identity. The use of traditional media (over digital media) predicted higher trust in government and system justification, but not national identity. Implications regarding recent protests in Hong Kong, tightening media control, and social movements on social media are discussed.
Interviews with patients aged 6–17 years provide valuable insights for physicians who need to deliver an epilepsy diagnosis
Authors: Jeschke Sarah , Woltermann Sarah , Neininger Martina Patrizia , Pauschek Josefine , Kiess Wieland , Bertsche Thilo , Bertsche Astrid
Published: November 2020

Aim

Meeting children's needs when communicating an epilepsy diagnosis can have a large impact on their treatment. We investigated children's experiences and wishes concerning their first conversation about epilepsy.

Methods

This prospective study was performed in the neuropaediatric departments of two German university hospitals from 2 October 2018 to 12 April 2019. The semi‐structured interview contained open questions, and multiple answers were allowed.

Results

We interviewed 101 patients (57 male) aged 6–17 (median 11) years and asked them to put themselves in the place of a physician delivering an epilepsy diagnosis. They said they would be careful and friendly and consider the children's feelings (29%), give them detailed information about their condition (29%) and reduce their fears and offer hope (26%). They would tell them the importance of always taking their medication and explain why (25%), make sure that the conversation took place in a comfortable setting (21%), explain any safety precautions (19%), keep the conversation straightforward and provide examples (16%).

Conclusion

Children with epilepsy provided concrete recommendations for physicians delivering an epilepsy diagnosis, with regard to the ideal setting, important topics and optimal communication. The recommendations could help physicians meet children's needs.