bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitigation of the age-dependent decline in mitochondrial genome integrity
Authors: Tsai Pei-I , Korotkevich Ekaterina , O’Farrell Patrick H. 
Published: January 2022

AbstractUnknown processes promote accumulation of mitochondrial DNA mutations during aging. Accumulation of defective mitochondrial genomes is thought to promote progression of heteroplasmic mitochondrial diseases and degenerative changes with natural aging. We used a heteroplasmic Drosophila model to test 1) whether purifying selection acts to limit the abundance of deleterious mutations during development and aging, 2) whether quality control pathways contribute to purifying selection, 3) whether activation of quality control can mitigate accumulation of deleterious mutations, and 4) whether improved quality control improves healthspan. We show that purifying selection operates during development and growth, but is ineffective during aging. Genetic manipulations suggest that a quality control process known to enforce purifying selection during oogenesis also suppresses accumulation of a deleterious mutation during growth and development. Flies with nuclear genotypes that enhanced purifying selection sustained higher genome quality, retained more vigorous climbing activity and lost fewer dopaminergic neurons. Pharmacological enhancement of quality control produced similar benefits. Importantly, similar pharmacological treatment of aged mice reversed age-associated accumulation of a deleterious mtDNA mutation. Our findings reveal dynamic maintenance of mitochondrial genome fitness, and reduction in the effectiveness of purifying selection during life. Importantly, we describe interventions that mitigate and even reverse age-associated genome degeneration in flies and in mice. Furthermore, mitigation of genome degeneration improved wellbeing in a Drosophila model of heteroplasmic mitochondrial disease.Significance StatementIn contrast to the orderly segregation of nuclear DNA, mitochondrial genomes compete for replication and segregation. The abundance of mutants that emerge in a cell depends on their success in this competition. We show that quality control mechanisms put deleterious mutations at a disadvantage, but these mechanisms become ineffective during aging. The resulting rise in mutant genomes, which compromises vigor, can be suppressed using genetic backgrounds that enhance quality control. Feeding kinetin to adult Drosophila or mice also reduced the load of mutant mitochondrial genomes. This pharmacological reversal of the age associated deterioration of mtDNA quality suggests possible therapies to alleviate mitochondrial diseases and normal aging.
Longitudinal Assessment of SARS-CoV-2 Specific T Cell Cytokine-Producing Responses for 1 Year Reveals Persistence of Multi-Cytokine Proliferative Responses, with Greater Immunity Associated with Disease Severity
Authors: Lin Jonah , Law Ryan , Korosec Chapin S. , Zhou Christine , Koh Wan Hon , Ghaemi Mohammad Sajjad , Samaan Philip , Ooi Hsu Kiang , Yue FengYun , Gingras Anne-Claude , Estacio Antonio , Buchholz Megan , Cheatley Patti Lou , Pavinski Katerina , Mubareka Samira , McGeer Allison J. , Leis Jerome A. , Heffernan Jane M. , Ostrowski Mario 
Published: January 2022

AbstractCellular-mediated immunity is critical for long-term protection against most viral infections, including coronaviruses. We studied 23 SARS-CoV-2-infected survivors over a one year post symptom onset (PSO) interval by ex vivo cytokine ELISpot assay. All subjects demonstrated SARS-CoV-2-specific IFN-γ, IL-2, and Granzyme B (GzmB) T cell responses at presentation, with greater frequencies in severe disease. Cytokines, mainly produced by CD4+ T cells, targeted all structural proteins (Nucleocapsid, Membrane, Spike) except Envelope, with GzmB > IL-2 > IFN-γ. Mathematical modeling predicted that: 1) cytokine responses peaked at 6 days for IFN-γ, 36 days for IL-2, and 7 days for GzmB, 2) severe illness was associated with reduced IFN-γ and GzmB, but increased IL-2 production rates, 3) males displayed greater production of IFN-γ, whereas females produced more GzmB. Ex vivo responses declined over time with persistence of IL-2 in 86% and of IFN-γ and GzmB in 70% of subjects at a median of 336 days PSO. The average half-life of SARS-CoV-2-specific cytokine-producing cells was modelled to be 139 days (∼4.6 months). Potent T cell proliferative responses persisted throughout observation, were CD4 dominant, and were capable of producing all 3 cytokines. Several immunodominant CD4 and CD8 epitopes identified in this study were shared by seasonal coronaviruses or SARS-CoV-1 in the Nucleocapsid and Membrane regions. Both SARS-CoV-2-specific CD4+ and CD8+ T cell clones were able to kill target cells, though CD8 tended to be more potent.ImportanceOur findings highlight the relative importance of SARS-CoV-2-specific GzmB-producing T cell responses in SARS-CoV-2 control, shared CD4 and CD8 immunodominant epitopes in seasonal coronaviruses or SARS-CoV-1, and indicate robust persistence of T cell memory at least one year after infection. Our findings should inform future strategies to induce T cell vaccines against SARS-CoV-2 and other coronaviruses.
Monitoring SARS-CoV-2 genome evolution in a localized population
Authors: Gupta Asmita , Basu Reelina , Bashyam Murali Dharan 
Published: January 2022

AbstractDespite seminal advances towards understanding its infection mechanism, SARS-CoV-2 continues to cause significant morbidity and mortality worldwide. Though mass immunization programs have been implemented in several countries, the viral transmission cycle has shown a continuous progression in the form of multiple waves. A constant change in the frequencies of dominant viral lineages, arising from the accumulation of nucleotide variations (NVs) through favourable selection, is understandably expected to be a major determinant of disease severity and possible vaccine escape. Indeed, worldwide efforts have been initiated to identify specific virus lineage(s) and/or NVs that may cause a severe clinical presentation or facilitate vaccination breakthrough. Since host genetics is expected to play a major role in shaping virus evolution, it is imperative to study role of genome-wide SARS-CoV-2 NVs across various populations. In the current study, we analysed the whole genome sequence of 3543 SARS-CoV-2 infected samples obtained from the state of Telangana, India (including 210 from our previous study), collected over an extended period from April, 2020 to October, 2021. We present a unique perspective on the evolution of prevalent virus lineages and NVs during this time period. We also highlight presence of specific NVs likely to be associated favourably with samples classified as vaccination breakthroughs. Finally, we report genome-wide intra-host variations (iSNVs) at novel genomic positions. The results presented here provide critical insights into virus evolution over an extended time period within a geographically restricted area and pave the way to rigorously investigate the role of specific NVs in vaccination breakthroughs.
Heterogeneity in Neuronal Dynamics is Learned by Gradient Descent for Temporal Processing Tasks
Authors: Winston Chloe N. , Mastrovito Dana , Shea-Brown Eric , Mihalas Stefan 
Published: January 2022

AbstractIndividual neurons in the brain have complex intrinsic dynamics that are highly diverse. We hypothesize that the complex dynamics produced by networks of complex and heterogeneous neurons may contribute to the brain’s ability to process and respond to temporally complex data. To study the role of complex and heterogeneous neuronal dynamics in network computation, we develop a rate-based neuronal model, the generalized-leaky-integrate-and-firing-rate (GLIFR) model, which is a rate-equivalent of the generalized-leaky-integrate-and-fire model. The GLIFR model has multiple dynamical mechanisms which add to the complexity of its activity while maintaining differentiability. We focus on the role of after-spike currents, currents induced or modulated by neuronal spikes, in producing rich temporal dynamics. We use machine learning techniques to learn both synaptic weights and parameters underlying intrinsic dynamics to solve temporal tasks. The GLIFR model allows us to use standard gradient descent techniques rather than surrogate gradient descent, which has been utilized in spiking neural networks. After establishing the ability to optimize parameters using gradient descent in single neurons, we ask how networks of GLIFR neurons learn and perform on temporally challenging tasks, such as sinusoidal pattern generation and sequential MNIST. We find that these networks learn a diversity of parameters, which gives rise to diversity in neuronal dynamics. We also observe that training networks on the sequential MNIST task leads to formation of cell classes based on the clustering of neuronal parameters. GLIFR networks have mixed performance when compared to vanilla recurrent neural networks but appear to be more robust to random silencing. When we explore these performance gains further, we find that both the ability to learn heterogeneity and the presence of after-spike currents contribute. Our work both demonstrates the computational robustness of neuronal complexity and diversity in networks and demonstrates a feasible method of training such models using exact gradients.
PP1 phosphatases control PAR-2 localization and polarity establishment in C. elegans embryos
Authors: Calvi Ida , Schwager Françoise , Gotta Monica 
Published: January 2022

AbstractCell polarity relies on the asymmetric distribution of the conserved PAR proteins, which is regulated by phosphorylation/dephosphorylation reactions. While the kinases involved have been well studied, the role of phosphatases remains poorly understood. In C. elegans zygotes, phosphorylation of the posterior PAR-2 protein by the atypical protein kinase PKC-3 inhibits PAR-2 cortical localization. Polarity establishment depends on loading of PAR-2 at the posterior cortex. We show that the PP1 phosphatases GSP-1 and GSP-2 are required for polarity establishment in embryos. We find that co-depletion of GSP-1 and GSP-2 abrogates the cortical localization of PAR-2 and that GSP-1 and GSP-2 interact with PAR-2 via a PP1 docking motif in PAR-2. Mutating this motif in vivo, to prevent binding of PAR-2 to PP1, abolishes cortical localization of PAR-2, while optimizing this motif extends PAR-2 cortical localization. Our data suggest a model in which GSP-1/-2 counteract PKC-3 phosphorylation of PAR-2 allowing its cortical localization at the posterior and polarization of the one-cell embryo.SUMMARYCalvi et al. identify PP1 protein phosphatases as regulators of cell polarity in C. elegans embryos. Their results show that two redundant phosphatases, GSP-1 and GSP-2, interact with the polarity protein PAR-2 and control its localization and polarity establishment.
Genomic library of Bordetella
Authors: Bridel Sébastien , Bouchez Valérie , Brancotte Bryan , Hauck Sofia , Armatys Nathalie , Landier Annie , Mühle Estelle , Guillot Sophie , Toubiana Julie , Maiden Martin C.J. , Jolley Keith A. , Brisse Sylvain 
Published: January 2022

AbstractBackgroundThe re-emergence of whooping cough and geographic disparities in vaccine escape or antimicrobial resistance dynamics, underline the importance of a unified definition of Bordetella pertussis strains. Understanding of the evolutionary adaptations of Bordetella pathogens to humans and animals requires comparative studies with environmental bordetellae.MethodsWe have set-up a unified library of Bordetella genomes by merging previously existing Oxford and Pasteur databases, importing genomes from public repositories, and developing harmonized genotyping schemes. We developed a genus-wide cgMLST genotyping scheme and incorporated a previous B. pertussis cgMLST scheme. Specific schemes were developed to define antigenic, virulence and macrolide resistance profiles. Genomic sequencing of 83 French B. bronchiseptica isolates and of B. tumulicola, B. muralis and B. tumbae type strains was performed.ResultsThe public library currently includes 2,581 Bordetella isolates and their provenance data, and 2,084 genomes. The “classical Bordetella” (B. bronchiseptica, B. parapertussis and B. pertussis), which form a single genomic species (B. bronchiseptica genomic species, BbGS), were overrepresented (n=2,382). The phylogenetic analysis of Bordetella genomes associated the three novel species B. tumulicola, B. muralis and B. tumbae in a clade with B. petrii and revealed 18 yet undescribed species. A sister lineage of the classical bordetellae, provisionally named Bbs lineage II, was uncovered and may represent a novel species (average nucleotide identity with BbGS strains: ∼95%). It comprised strain HT200 from India, two strains of ‘genogroup 6’ from the USA and six clinical isolates from France; this lineage lacked ptxP and its fim2 gene was divergent. Within B. pertussis, vaccine antigen sequence types marked important phylogenetic subdivisions, and macrolide resistance markers (23S_rRNA allele 13 and fhaB3) confirmed the current restriction of this phenotype in China with few exceptions.ConclusionsThe genomic platform provides an expandable resource for unified genotyping of Bordetella strains and will facilitate collective evolutionary and epidemiological understanding of the re-emergence of whooping cough and other Bordetella infections.Data summaryBordetella genomes list and accession numbers: Supplementary Table S4Bordetella genus phylogeny dataset (92 isolates):https://bigsdb.pasteur.fr/cgi-bin/bigsdb/bigsdb.pl?db=pubmlst_bordetella_isolates&page=query&project_list=23&submit=1B. bronchiseptica phylogeny dataset (213 isolates):https://bigsdb.pasteur.fr/cgi-bin/bigsdb/bigsdb.pl?db=pubmlst_bordetella_isolates&page=query&project_list=24&submit=1B. pertussis phylogeny (124 isolates):https://bigsdb.pasteur.fr/cgi-bin/bigsdb/bigsdb.pl?db=pubmlst_bordetella_isolates&page=query&project_list=25&submit=1iTOL interactive trees: https://itol.embl.de/shared/1l7Fw0AvKOoCF
Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming
Authors: Chondronasiou Dafni , Gill Diljeet , Mosteiro Lluc , Urdinguio Rocio G. , Berenguer Antonio , Aguilera Monica , Durand Sylvere , Aprahamian Fanny , Nirmalathasan Nitharsshini , Abad Maria , Martin-Herranz Daniel E. , Otto-Attolini Camille Stephan , Prats Neus , Kroemer Guido , Fraga Mario F. , Reik Wolf , Serrano Manuel 
Published: January 2022

ABSTRACTThe expression of the pluripotency factors OCT4, SOX2, KLF4 and MYC (OSKM) can convert somatic differentiated cells into pluripotent stem cells in a process known as reprogramming. Notably, cycles of brief OSKM expression do not change cell identity but can reverse markers of aging in cells and extend longevity in progeroid mice. However, little is known about the mechanisms involved. Here, we have studied changes in the DNA methylome, transcriptome and metabolome in naturally aged mice subject to a single period of transient OSKM expression. We found that this is sufficient to reverse DNA methylation changes that occur upon aging in the pancreas, liver, spleen and blood. Similarly, we observed reversion of transcriptional changes, especially regarding biological processes known to change during aging. Finally, some serum metabolites altered with aging were also restored to young levels upon transient reprogramming. These observations indicate that a single period of OSKM expression can drive epigenetic, transcriptomic and metabolomic changes towards a younger configuration in multiple tissues and in the serum.
Active Predictive Coding Networks: A Neural Solution to the Problem of Learning Reference Frames and Part-Whole Hierarchies
Authors: Gklezakos Dimitrios C. , Rao Rajesh P. N. 
Published: January 2022

AbstractWe introduce Active Predictive Coding Networks (APCNs), a new class of neural networks that solve a major problem posed by Hinton and others in the fields of artificial intelligence and brain modeling: how can neural networks learn intrinsic reference frames for objects and parse visual scenes into part-whole hierarchies by dynamically allocating nodes in a parse tree? APCNs address this problem by using a novel combination of ideas: (1) hypernetworks are used for dynamically generating recurrent neural networks that predict parts and their locations within intrinsic reference frames conditioned on higher object-level embedding vectors, and (2) reinforcement learning is used in conjunction with backpropagation for end-to-end learning of model parameters. The APCN architecture lends itself naturally to multi-level hierarchical learning and is closely related to predictive coding models of cortical function. Using the MNIST, Fashion-MNIST and Omniglot datasets, we demonstrate that APCNs can (a) learn to parse images into part-whole hierarchies, (b) learn compositional representations, and (c) transfer their knowledge to unseen classes of objects. With their ability to dynamically generate parse trees with part locations for objects, APCNs offer a new framework for explainable AI that leverages advances in deep learning while retaining interpretability and compositionality.
Evaluating the impact of constraints on project success: empirical study of highway projects
Authors: Deep Shumank , Bhoola Vanita , Vidhani Jyoti , Hampannaver Pradeep Rajanna 
Published: January 2022

PurposeHighway projects in India have a history of cost overruns and delay in project delivery, thus incurring huge losses to public funds. The study aimed to measure the extent of influence of various constraints on the overall success of highway projects (e.g. National highway project, state highway projects and major district roads). Based on the literature, various factors were grouped under three categories (a) Project Constraints, (b) Project Governance Constraints and (c) Stakeholder Induced Constraints.Design/methodology/approachA quantitative approach was adopted. A questionnaire-based survey was conducted with 435 respondents from the field of highway projects with a minimum experience of 1 year as Project Manager. The data was analyzed by partial least squares structural equation modeling technique.FindingsIt was identified that the impact of project constraints (ES = 0.313) on project success is more than that of project governance constraints (ES = 0.231) and stakeholder induced constraints. Additionally, it was found that project governance constraints have a strong impact on project constraints (ES = 0.535) and stakeholder induced constraints (ES = 0.403).Originality/valueThe study presented in this paper is first of its kind to measure and articulate the impact of project governance constraint, project constraint and stakeholder induced constraints on project success.
“We have to take care of them”: front office workers and the secret sexual encounters of guests in high-end hotels
Authors: Gaspani Fabio 
Published: January 2022

PurposeIn line with the escapist dimension of hospitality settings, the article investigates how the front office staff of high-end hotels deal with clients' secret sexual encounters.Design/methodology/approachThe article draws on data collected through a participant observation study conducted in two high-end hotels in Milan (Italy), during which the author held the role of front-line receptionist.FindingsThe research illustrates the ways in which workers frame events and conduct operations to guarantee the appropriate conditions for guests' extra-marital adventures and paid sexual encounters. In revealing the role of shared knowledge as well as non-formalised procedures in meeting guests' needs, the article shows how employees seek to protect their own work and the hotel's image.Originality/valueThe article sheds light on the very features of high-end service work by illustrating how workers satisfy clients' secret needs and unexpressed demands.
Determinants of house prices in Malaysia
Authors: Alpha Kabine Camara 
Published: January 2022

Purpose
This paper aims to empirically examine the relationship between macroeconomic factors and housing prices in Malaysia from 1991 to 2016.

Design/methodology/approach
This study was based on annual macroeconomic data from 1991 to 2016. For the model that was constructed, house prices were treated as the dependent variable and other variables, namely, the interest rate, the gross domestic product (GDP) and the consumer price index (CPI) as explanatory or regression variables. All these data come from the annual publication of the World Bank’s statistical report. In the meantime, data on house prices have been obtained through the publication of the National Property Information Centre in the form of an index. In the study, the bounds testing approach for cointegration was used because the Engel Granger cointegration tests can be used only if all the series are stationary at first difference. And it is against this background the author could not use it because our variables are a combination of series integrated of orders I (0) and I (1).

Findings
The results of this study revealed a positive equilibrium relationship in the long run between interest rate, CPI and housing prices and negative for the GDP. In addition, in the short run, housing prices were shown to have a positive relationship with GDP and CPI, but no relationship with the interest rate, based on the assumption that “all other things being equal”.

Research limitations/implications
The data on economic factors (GDP, RI and CPI) used in this study are secondary and not from the Malaysian Department of Statistics and Economic Studies. Furthermore, the result of this research only reflects the Malaysian reality, and therefore, cannot be generalised to the entire housing market worldwide.

Practical implications
The result of this study can be used for housing valuation by Malaysian property market players, investors and especially policymakers.

Social implications
This study’s findings can help Malaysian policymakers to limit the high price fluctuation in the housing industry and help Malaysian citizens to buy their own homes at a reasonable price.

Originality/value
The contributions of this study are structured around two points. The first is the contribution to the body of knowledge, where the results of the study will contribute to the growing number of literature in the housing sector. Moreover, the second contribution of this document is the strength of its recommendation to policymakers. This is because it analyses only the main macroeconomic determinants (IR, GDP and CPI) that are essential to better influence the housing sector as quickly as possible, as opposed to those that use many variables that could lead to possible specification errors.
Psychological mechanism linking green human resource management to green behavior
Authors: Ye Jing , Zhang Xufan , Zhou Lulu , Wang Decai , Tian Feng 
Published: January 2022

PurposeThe purpose of this paper is to explore the psychological mechanism linking green human resource management (GHRM) to the in-role and extra-role green behavior of new employees.Design/methodology/approachBased on the AMO framework, the authors used three-wave survey data from 399 newcomers and 103 superiors in China. This study uses the bootstrapping approach with Mplus 7.0.FindingsThe analysis shows the direct effect of GHRM on the in-role and extra-role green behavior of new employees as well as the mediating effects between perceived insider status and perceived external prestige.Originality/valueThis study expands research on GHRM to the in-role and extra-role green behavior of new employees. This paper also enhances the understanding of green behaviors inside and outside the roles of new employees and provides scientific implications for the green development of organizations.