bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational study and design of effective siRNAs to silence structural proteins associated genes of Indian SARS-CoV-2 strains
Authors: Madanagopal Premnath , Muthukumar Harshini , Thiruvengadam Kothai 
Published: February 2022

AbstractSARS-CoV-2 is a highly transmissible and pathogenic coronavirus that first emerged in late 2019 and has since triggered a pandemic of acute respiratory disease named COVID-19 which poses a significant threat to all public health institutions in the absence of specific antiviral treatment. Since the outbreak began in March 2020, India has reported 4.77 lakh Coronavirus deaths, according to the World Health Organization (WHO). The innate RNA interference (RNAi) pathway, on the other hand, allows for the development of nucleic acid-based antiviral drugs in which complementary small interfering RNAs (siRNAs) mediate the post-transcriptional gene silencing (PTGS) of target mRNA. Therefore, in this current study, the potential of RNAi was harnessed to construct siRNA molecules that target the consensus regions of specific structural proteins associated genes of SARS-CoV-2, such as the envelope protein gene (E), membrane protein gene (M), nucleocapsid phosphoprotein gene (N), and surface glycoprotein gene (S) which are important for the viral pathogenesis. Conserved sequences of 811 SARS-CoV-2 strains from around India were collected to design 21 nucleotides long siRNA duplex based on various computational algorithms and parameters targeting E, M, N and S genes. The proposed siRNA molecules possessed sufficient nucleotide-based and other features for effective gene silencing and BLAST results revealed that siRNAs’ targets have no significant matches across the whole human genome and hence, siRNAs were found to have no off-target effects on the genome, ruling out the possibility of off-target silencing. Finally, out of 157 computationally identified siRNAs, only 4 effective siRNA molecules were selected for each target gene which is proposed to exert the best action based on GC content, free energy of folding, free energy of binding, melting temperature, heat capacity and molecular docking analysis with Human AGO2 protein. Our engineered siRNA candidates could be used as a genome-level therapeutic treatment against various sequenced SARS-CoV-2 strains in India. However, future applications will necessitate additional validations in vitro and in vivo animal models.
Neutrophils degranulate GAG-containing proteoglycofili, which block Shigella growth and degrade virulence factors
Authors: André Antonin C , Barroso Marina Valente , Skerniskyte Jurate , Siegwald Mélina , Paul Vanessa , Debande Lorine , Ridley Caroline , Svahn Isabelle , Rigaud Stéphane , Tinevez Jean-Yves , Vivès Romain R , Sansonetti Philippe J , Thornton David J , Marteyn Benoit S 
Published: February 2022

Summary paragraphNeutrophil degranulation plays a central role in their ability to kill pathogens but also to stimulate other immune cells1–3. Here we show that neutrophil degranulation, induced in hypoxia or upon Shigella infection in vitro and in vivo, leads to the release of polymers called neutrophil Proteoglycofili (PGF). PGF are mainly composed of granular proteins (myeloperoxidase, elastase, lactoferrin, cathelicidin, albumin) pre-stored in various types of granules, and chondroitin sulfate. PGF individual fibers have a diameter of 43.9 ± 20.3 nm and. They secreted by viable neutrophils and do not contain DNA, as opposed to NETs which contains also granular proteins, chondroitin sulfate in addition to chromatin, released upon neutrophil disintegration and cell death.We demonstrated that PGF block the growth of Shigella and other bacteria and degrade Shigella virulence factors. The degradation of the chondroitin sulfate polymers with testes hyaluronidases destabilizes PGF ultrastructure and abolishes its antimicrobial activity. Our results provide novel insights in the neutrophil degranulation process and open new doors for the investigation of PGF contribution to cytokines concentration gradient formation and adaptive immune cells activation. Further investigations are required to better appreciate the importance of this “sterile blaster” in infectious or inflammatory diseases.
Novel method for multiplexed full-length single-molecule sequencing of the human mitochondrial genome
Authors: Keraite Ieva , Becker Philipp , Canevazzi Davide , Frias-López Maria C. , Dabad Marc , Tonda-Hernandez Raúl , Paramonov Ida , Ingham Matthew John , Brun-Heath Isabelle , Leno Jordi , Abulí Anna , Garcia-Arumí Elena , Heath Simon , Gut Marta , Gut Ivo Glynne 
Published: February 2022

AbstractMethods to reconstruct the mitochondrial DNA (mtDNA) sequence using short-read sequencing come with an inherent bias due to amplification and mapping. They can fail to determine the phase of variants, to capture multiple deletions and to cover the mitochondrial genome evenly. Long-read whole genome sequencing is prohibitively expensive for mtDNA heteroplasmy detection and often does not recapitulate the full mtDNA length.Here we describe a method to target, multiplex and sequence full-length, native single-molecule the human mitochondrial genome utilizing the RNA-guided DNA endonuclease Cas9. Combining Cas9 induced breaks as barcodes with long-read sequencing, we implemented a protocol in an optimal setting for both high or low integrity genomic DNA to target the circular mitochondrial genome with extremely high coverage. Our analytical pipeline efficiently detects single nucleotide heteroplasmy, physically determines phase and can accurately disentangle complex deletion patterns. This workflow is a unique tool for studying mtDNA variation in health and disease, and will accelerate mitochondrial research.
Impact of cell culture on the transcriptomic programs of primary and iPSC-derived human alveolar type 2 cells
Authors: Alysandratos Konstantinos-Dionysios , de Alba Rivas Carolina Garcia , Yao Changfu , Pessina Patrizia , Villacorta-Martin Carlos , Huang Jessie , Hix Olivia T. , Minakin Kasey , Konda Bindu , Stripp Barry R. , Kim Carla F. , Kotton Darrell N. 
Published: February 2022

SummaryThe alveolar epithelial type 2 cell (AEC2) is the facultative progenitor of lung alveoli tasked to maintain distal lung homeostasis. AEC2 dysfunction has been implicated in the pathogenesis of a number of pulmonary diseases, including idiopathic pulmonary fibrosis (IPF), highlighting the importance of human in vitro models of the alveolar epithelium. However, AEC2-like cells captured in cell culture have yet to be directly compared to their in vivo counterparts at single cell resolution. Here, we apply single cell RNA sequencing to perform head-to-head comparisons between the global transcriptomes of freshly isolated primary (1°) adult human AEC2s, their isogenic cultured progeny, and human iPSC-derived AEC2s (iAEC2s) cultured in identical conditions. We find each population occupies a distinct transcriptomic space with both types of cultured AEC2s (1° and iAEC2s) exhibiting similarities to and differences from freshly purified 1° cells. Across each cell type, we find an inverse relationship between proliferative states and AEC2 maturation states, with uncultured 1° AEC2s being most quiescent and mature, their cultured progeny being more proliferative/less mature, and cultured iAEC2s being most proliferative/least mature. iAEC2s also express significantly lower levels of major histocompatibility complex (MHC) genes compared to 1° cells, suggesting immunological immaturity. Cultures of either type of human AEC2 (1° or iAEC2) do not generate detectable type 1 alveolar cells in these defined conditions; however, iAEC2s after co-culture with fibroblasts can give rise to a subset of cells expressing “transitional cell markers” recently described in fibrotic lung tissue of patients with pulmonary fibrosis or in mouse models of pulmonary fibrosis. Hence, we provide direct comparisons of the transcriptomic programs of 1° and engineered AEC2s, two in vitro model systems that can be harnessed for studies of human lung health and disease.
N-phosphonacetyl-L-aspartate enhances type I interferon anti-viral responses through activation of non-canonical NOD2 signaling
Authors: Ponti András K. , Zangara Megan T. , O’Connor Christine M. , Johnson Erin E. , McDonald Christine 
Published: February 2022

AbstractType I interferon production and the expression of interferon-stimulated genes (ISGs) are key components of an innate immune response to many microbial pathogens. Dysregulation of this response can result in uncontrolled infection, inflammation, and autoimmune disease. Understanding the molecular mechanisms shaping the strength of type I interferon signaling may provide critical insights into infection control strategies and autoimmune disease therapies. Nucleotide-binding oligomerization domain 2 (NOD2) is an intracellular pattern recognition receptor that acts as both a bacterial sensor protein and a mediator of antiviral responses. Antibacterial functions of NOD2 are enhanced by treatment with the small molecule inhibitor of pyrimidine biosynthesis N-phosphonacetyl-L-aspartate (PALA), though how this might function in the host antiviral response remains unknown. Therefore, we tested the ability of PALA to enhance NOD2-dependent antiviral responses. Alone, PALA treatment of macrophages was not sufficient to induce interferon β (IFNβ) production or ISG expression. Instead, PALA synergized with IFNβ stimulation to enhance expression and activation of interferon-stimulated gene factor 3 (ISGF3) and induce the upregulation of a subset of ISGs in co-treated cells. Furthermore, PALA treatment of epithelial cells resulted in impaired viral replication of the herpesvirus, human cytomegalovirus. Induction of the PALA-enhanced antiviral response required activation of non-canonical NOD2 signaling mediated by mitochondrial antiviral-signaling protein (MAVS) and interferon response factor 1 (IRF1), rather than the classical receptor-interacting serine/threonine protein kinase 2 (RIP2) pathway or other IRFs previously reported to mediate NOD2 antiviral responses. These findings highlight pyrimidine metabolism enzymes as controllers of antimicrobial responses and suggest novel mechanisms for the modulation of type I interferon responses and antiviral activity.Significance StatementUnderstanding the molecular mechanisms shaping the strength of type I interferon signaling may provide critical insights to improve infection control strategies and autoimmune disease therapies. This work demonstrates that the pyrimidine synthesis inhibitor N-phosphonacetyl-L-aspartate synergizes with type I interferon to enhance antiviral responses through activation of a non-canonical NOD2 signaling pathway. These findings highlight pyrimidine metabolism enzymes as controllers of antimicrobial responses and suggest novel mechanisms for the modulation of type I interferon responses.
Capacity and tradeoffs in neural encoding of concurrent speech during Selective and Distributed Attention
Authors: Kaufman Maya , Golumbic Elana Zion 
Published: February 2022

AbstractSpeech comprehension is severely compromised when several people talk at once, due to limited perceptual and cognitive resources. Under some circumstances listeners can employ top-down attention to prioritize the processing of task-relevant speech. However, whether the system can effectively represent more than one speech input remains highly debated.Here we studied how task-relevance affects the neural representation of concurrent speakers under two extreme conditions: when only one speaker was task-relevant (Selective Attention), vs. when two speakers were equally relevant (Distributed Attention). Neural activity was measured using magnetoencephalography (MEG) and we analysed the speech-tracking responses to both speakers. Crucially, we explored different hypotheses as to how the brain may have represented the two speech streams, without making a-priori assumptions regarding participants’ internal allocation of attention.Results indicate that neural tracking of concurrent speech did not fully mirror their instructed task-relevance. When Distributed Attention was required, we observed a tradeoff between the two speakers despite their equal task-relevance, akin to the top-down modulation observed during Selective Attention. This points to the system’s inherent limitation to fully process two speech streams, and highlights the complex nature of attention, particularly for continuous speech.
Pairing-dependent plasticity in a dissected fly brain is input-specific and requires synaptic CaMKII enrichment and nighttime sleep
Authors: Adel Mohamed , Chen Nannan , Zhang Yunpeng , Reed Martha L. , Quasney Christina , Griffith Leslie C. 
Published: February 2022

AbstractIn Drosophila, in vivo functional imaging studies revealed that associative memory formation is coupled to a cascade of neural plasticity events in distinct compartments of the mushroom body (MB). In-depth investigation of the circuit dynamics, however, will require an ex vivo model that faithfully mirrors these events to allow direct manipulations of circuit elements that are inaccessible in the intact fly. The current ex vivo models have been able to reproduce the fundamental plasticity of aversive short-term memory, a potentiation of the MB intrinsic neurons (Kenyon cells; KCs) responses after artificial learning ex vivo. However, this potentiation showed different localization and encoding properties from those reported in vivo and failed to generate the previously reported suppression plasticity in the mushroom body output neurons (MBONs). Here, we develop an ex vivo model using the female Drosophila brain that recapitulates behaviorally evoked plasticity in the KCs and MBONs. We demonstrate that this plasticity accurately localizes to the MB α’3 compartment and is encoded by a coincidence between KCs activation and dopaminergic input. The formed plasticity is input-specific, requiring pairing of the conditioned stimulus (CS) and unconditioned stimulus (US) pathways; hence we name it pairing-dependent plasticity (PDP). PDP formation requires an intact CaMKII gene and is blocked by previous-night sleep deprivation but is rescued by rebound sleep. In conclusion, we show that our ex vivo preparation recapitulates behavioral and imaging results from intact animals and can provide new insights into mechanisms of memory formation at the level of molecules, circuits, and brain state.Significance StatementThe mammalian ex vivo LTP model enabled in-depth investigation of the hippocampal memory circuit. We develop a parallel model to study the Drosophila mushroom body (MB) memory circuit. Pairing activation of the conditioned stimulus and unconditioned stimulus pathways in dissected brains induces a potentiation pairing-dependent plasticity (PDP) in the axons of α’β’ Kenyon cells and a suppression PDP in the dendrites of their postsynaptic MB output neurons, localized in the MB α’3 compartment. This PDP is input-specific and requires the 3’ untranslated region of CaMKII. Interestingly, ex vivo PDP carries information about the animal’s experience before dissection; brains from sleep deprived animals fail to form PDP while those from animals who recovered 2 hours of their lost sleep form PDP.
Combustion analysis of biodiesel-powered propeller engine for least environmental concerns in aviation industry
Authors: V. Balaji , S. Kaliappan , D.M. Madhuvanesan , D.S. Ezhumalai , S. Boopathi , Pravin P. Patil , Mani Saiprakash 
Published: February 2022

Purpose
The purpose of the study is to examine the influence of the corn biofuel on the Jet engine. Each tests were carried out in a small gas turbine setup. The performance characteristics of thrust, thrust-specific fuel consumption, exhaust gas temperature and emission characteristics of Carbon monoxide(CO), Carbon dioxide (CO2), Oxygen (O2), Unburned hydrocarbons (UHC) and Nitrogen of oxides (NO) emissions were measured and compared with Jet-A fuel to find the suitability of the biofuel used.

Design/methodology/approach
Upgrading and using biofuels in aviation sector have been emerging as a fruitful method to diminish the CO emission into the atmosphere. This research paper explores the possibility of using nanoparticles-enriched bio-oil as a fuel for jet engines. The biofuel taken is corn oil and the added nanoparticles are Al2O3.

Findings
The biofuel blends used are B0 (100% Jet-A fuel), B10 (10 % corn oil biofuel + 90% Jet-A fuel), B20 (20% corn oil biofuel + 80% Jet-A fuel) and B30 (30% corn oil biofuel + 70% Jet-A fuel). All fuel blends were mixed with the moderate dosage level of 30 ppm. All tests were conducted at different rpm as 50,000, 60,000, 70,000 and 80,000 rpm.

Originality/value
The results proved that within the lower limit, use of biofuel increased the performance characteristics and reduced the emission characteristics except the emission of NO. The moderate-level biofuel with Jet-A fuel showed the equally better performance to the neat Jet-A fuel.
Exploring the relationship between plot size and fertilizer use efficiency: evidence from large-scale farming in China
Authors: Li Fang , Feng Shuyi , Lu Hualiang , Qu Futian , D'Haese Marijke 
Published: February 2022

PurposeThis paper investigates the relationship between plot size and fertilizer use efficiency (FE) in Chinese large-scale farming and searches for the underlying mechanisms that explain this relationship.Design/methodology/approachBased on a household- and plot-level data set of large-scale production units (LSPUs) from Jiangsu and Jiangxi Provinces, the technical and fertilizer use efficiency of large-scale rice production is estimated by applying a translog stochastic frontier production function. The authors impose a monotonicity condition on the translog frontier using a three-step procedure to get theoretically consistent efficiency estimates. A beta regression model is then used to explore the association between plot size and LSPUs' efficiency in fertilizer application.FindingsThe average FE for the sampled plots is around 30%, which shows a large potential for LSPUs to reduce fertilizer use. A U-shaped relationship is observed between plot size and FE. The authors relate this non-linear pattern to the substitution of labour with capital-intensive technology and the efficiency differences in terms of farming performance between family and hired workers.Originality/valueFirst, according to the authors’ knowledge, this paper is a first attempt to study the size–efficiency relationship focussing on fertilization practices of large-scale farming. The second contribution lies in the large-scale ranges of the plot-level data set. Third, efforts are made to reveal the mechanisms determining the plot size–FE relationship. Fourth, the authors provide guiding evidence for policymaking, as they show that the size of individual plots deserves equal attention in land consolidation decisions. Methodologically, this paper improves existing estimates of single-factor technical efficiency issued from a restricted production frontier model.
Role of information and communication technologies in Build Back Better to post disaster recovery practices: insights from Bangladesh
Authors: Shuvo Sakib Rahman Siddique , Islam Md. Nurul , Islam Sheikh Tawhidul 
Published: February 2022

Purpose
This study aims to examine the role of information and communication technology (ICT)-based communication technologies to create a sustainable recovery strategy through Build Back Better practice in the existing policy framework of Bangladesh. Its purpose is to analyse the problems associated with the current recovery process of the country and how the ICT-based communication technology can improve the situation. Nevertheless, the aim also extends towards the limitation of the technology and the infrastructures and possible adjustments in this regard.

Design/methodology/approach
To achieve the aim, the study conducted an extensive literature review of numerous grey literature, policy papers and scientific/academic articles in an exploratory approach.

Findings
The result shows that the disaster recovery process of Bangladesh is slow, and there are some mismanagements (the lengthy risk assessment using ancient data generation processes, lack of accessibility and report-based data product) which was a cause behind the massive destruction done by recent cyclones. The ICT-based methods (proper database, many to many communications, GIS) can make this response faster, transparent and easy to access.

Research limitations/implications
The research results may lack generalizability due to the research approach of the study. Thus, researchers are encouraged to test the proposed propositions further.

Practical implications
The study includes some possible adjustments to the argument for the existing policy infrastructure and scope of communication technology to bridge the theory and practice.

Social implications
The study also includes some suggestions to engage society in disaster recovery processes.

Originality/value
This paper urges to study the implication of technology in terms of disaster recovery on a broad scale.
Retaliation for whistleblowing: some case studies on the experience of re-employment/redeployment
Authors: Lewis David 
Published: February 2022

Purpose
Courts and tribunals seem to have little knowledge about what factors make re-employment practicable. This paper aims to demonstrate that the re-employment/redeployment of whistleblowers may well be “successful” in a wide range of circumstances.

Design/methodology/approach
Interviewees were identified via a direct call to organisations involved in advising or representing whistleblowers. Covid restrictions at the time (March–April 2021) prevented case study interviews being conducted in person, so Zoom interviews were carried out.

Findings
The “success” of re-employment/ redeployment was associated with the following factors: the individual returned to the same job with a different boss or at a different location; the concern raised was dealt with; there had been judicial involvement by way of mediation and/or adjudication; that lawyers were used as representatives; that most returnees were not financially worse off; that the individual had the support of family, friends and colleagues and were willing to get the press or other media involved.

Research limitations/implications
As the findings are based on 11 interviews arising from snowball sampling, it goes without saying that they cannot be considered representative, and more extensive research is needed to check their validity. It should also be noted that the positive views expressed about re-employment/redeployment may reflect the fact that those who had more negative experiences of returning to work were less likely to volunteer to be interviewed. The author believes that this research demonstrates that a phenomenological approach can provide important insights into the highly complex nature of both retaliation for whistleblowing and any re-employment/ redeployment that ensures.

Practical implications
That factors could be identified, which might be associated with “successful” re-employment/ redeployment, has implications for both legal and human resource practitioners and perhaps for a wider society that believes those who suffer a wrong should have a say in the remedy that they are afforded.

Originality/value
To the author’s knowledge, almost no research has been carried out into the experiences of whistleblowers who have been reemployed/redeployed following retaliation for raising concerns.