bluuebunny/crossref_metadata_2025 huggingface dataset:
Lyrical Matters and Posthuman Poetics in Anne Carson’s Nox
Authors: Kosick Rebecca
Published: May 2021

Focused on Anne Carson’s Nox, this chapter address the relationships between lyric and matter, person and poem. It argues that Nox, an accordion-fold book in a box composed as an elegy to the poet’s brother Michael, constitutes a materialisation of the famous Roman lyric, Catullus 101. Rather than antagonising or excising the lyric, as prior approaches to material poetics had done, Nox turns 101’s described relations into material ones. The poem and its translations join with the textual remnants left behind by Carson’s brother – letters, photographs, recounted speech – to constitute a posthuman elegy, made from the matters of lyric and life. This chapter argues that contemporary material poetry, as Nox represents it, counters the assumption that practices akin to concrete poetry died after the mid-twentieth century, or were resurrected solely as a reaction to the digital age. As the examples in this book show, practices in material poetry continued steadily through the decades and went on to demonstrate elasticity and endurance. Nox, in particular, exhibits an ability to materially incorporate apparently antagonistic poetic types as the very matter of its poetics.
The Wounds of Rhetoric: Derrida on Condillac and Rousseau
Authors: Gaston Sean
Published: May 2021

The publication of Derrida's fragment Le Calcul des langues — Distyle offers an insight into Derrida's negotiation with empiricism and his rethinking of rhetoric in the early 1970s. Delineating Condillac's pervasive idealization of empiricism, Derrida gestures to a pain-becoming-pleasure and pleasure-becoming-pain that resists the fixed identity of the proper body. His emphasis on the pains and wounds of rhetoric registers both the limits of Condillac's philosophical project (rhetoric re-marks the excess of metaphor and the sensuous origins of language) and the possibility of another kind of empiricism, of the gaps that border on the word and the body. The article includes a reading of rhetoric and sex in Rousseau, as a gesture to Derrida's still unpublished seminar on rhetoric. It closes with an examination of the two-columned nature of Derrida's work, which ends mid-word (on the left) and mid-sentence (on the right).
The Ordinary Contested, Laruelle contra Deleuze and Guattari
Authors: Sackin-Poll Andrew
Published: May 2021

This article addresses the question of the relationship between corporeality and the ordinary in the works of François Laruelle. This is done through the formulation of the ‘ordinary body’ that draws from across Laruelle's work on the ordinary, corporeality and photography in order to outline Laruelle's radically immanent account of embodiment. The critical outline of Laruellean corporeality and the ordinary body is drawn out via a critical posing of Laruelle in contrast to Deleuze and Guattari. In doing so, the article indicates the singular difference between Laruelle, on one side, and Deleuze and Guattari, on the other, with respect to corporeal immanence and the usage of the everyday and ordinary. The article concludes with an argument that the relationship between the body and the ordinary in Laruelle's thought implies a novel non-philosophical or non-standard ‘poetics’ and usage of the ordinary.
An Effective Method for Parameter Estimation of Solar PV Cell Using Grey-Wolf Optimization Technique
Authors: Sharma Abhishek , Sharma Abhinav , Moshe Averbukh , Raj Nikhil , Pachauri Rupendra Kumar
Published: May 2021

In the field of renewable energy, the extraction of parameters for solar photovoltaic (PV) cells is a widely studied area of research. Parameter extraction of solar PV cell is a highly non-linear complex optimization problem. In this research work, the authors have explored grey wolf optimization (GWO) algorithm to estimate the optimized value of the unknown parameters of a PV cell. The simulation results have been compared with five different pre-existing optimization algorithms: gravitational search algorithm (GSA), a hybrid of particle swarm optimization and gravitational search algorithm (PSOGSA), sine cosine (SCA), chicken swarm optimization (CSO) and cultural algorithm (CA). Furthermore, a comparison with the algorithms existing in the literature is also carried out. The comparative results comprehensively demonstrate that GWO outperforms the existing optimization algorithms in terms of root mean square error (RMSE) and the rate of convergence. Furthermore, the statistical results validate and indicate that GWO algorithm is better than other algorithms in terms of average accuracy and robustness. An extensive comparison of electrical performance parameters: maximum current, voltage, power, and fill factor (FF) has been carried out for both PV model.
Propose a Polynomial Time Algorithm for Total Completion Time Objective
Authors: Ozturkoglu Yucel , Ozturkoglu Omer
Published: May 2021

In this study, we integrate deteriorate jobs with repair&maintenance activity on a single machine scheduling subject to total completion time. This work has more than one motivation. First, jobs are assigned to machines in an automated production line. Later, to schedule the maintenance activities, if needed, to prevent machinery from breaking down later. There are some important mathematical models to solve this combination. However, due to the complexity of the problem which is Np-hard, a polynomial algorithm should be needed for solving large problems. Therefore, this article introduces several polnomial algorithms to determine the order of things best. With using these algorithms, it will be possible to determine where to assign to the schedule, taking into account the number of maintenance activities required and their optimum total completion time.
Age Dependent Analysis of Colon Cancer Tumours Using Mathematical and Statistical Modelling
Authors: Machavaram Vidya Bhargavi , Veeramachaneni Sireesha
Published: May 2021

Colon cancer is the third most commonly diagnosed cancer and the second leading cause of cancer death in men and women combined in the United States. In this work, we performed mathematical and statistical modelling of Tumour sizes as a function of age for four different races. Mathematically, based on the behaviour of the data for each race, we partitioned ages of subjects into several intervals. The mathematical function that characterizes the size of the Tumour as a function of age was determined for each age interval. Statistically, using quantile regression, we designed models that are more robust at specific quantiles using Tumour size and age as dependent and predictor variables.
CRISPR/Cas9 Gene-Editing in Cancer Immunotherapy: Promoting the Present Revolution in Cancer Therapy and Exploring More
Authors: Ou Xuejin , Ma Qizhi , Yin Wei , Ma Xuelei , He Zhiyao
Published: May 2021

In recent years, immunotherapy has showed fantastic promise in pioneering and accelerating the field of cancer therapy and embraces unprecedented breakthroughs in clinical practice. The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (CRISPR-Cas9) system, as a versatile gene-editing technology, lays a robust foundation to efficiently innovate cancer research and cancer therapy. Here, we summarize recent approaches based on CRISPR/Cas9 system for construction of chimeric antigen receptor T (CAR-T) cells and T cell receptor T (TCR-T) cells. Besides, we review the applications of CRISPR/Cas9 in inhibiting immune checkpoint signaling pathways and highlight the feasibility of CRISPR/Cas9 based engineering strategies to screen novel cancer immunotherapy targets. Conclusively, we discuss the perspectives, potential challenges and possible solutions in this vivid growing field.
Exploring Sonic Meaning and Embodiment in Human Cultural Transmission From a Pedagogical Perspective
Authors: Rinsema Rebecca , Edwards Jashen
Published: May 2021

The authors explore how sonic materials, specifically everyday sounds and songs, create and communicate personal, sociocultural, and ecological meanings. From the lulling passages of a pastoral movement streaming through a symphony hall to the rollicking screams at stadium concerts to the roaring rhetoric and social distortions of divisive political-speak, sound and music signal frequencies and frictions at play in the human experience. Literacies are cultivated, sounds embodied, and ways of sensing, knowing, and being in the world are sonically communicated and established. What happens when sounds encountered in one’s everyday experience are excavated, sampled, and remixed?. What new meanings may be derived? What old meanings might be challenged and reconstituted and reconstructed into new forms of knowing and being? What happens when songs or timeless tunes are analyzed and detangled from their ordinary meanings? How might listeners make the familiar strange and thus renew knowings? And what does any of this mean for the flux and firmness of human cultures in motion?
Inter-Cohort Validation of SuStaIn Model for Alzheimer’s Disease
Authors: Archetti Damiano , Young Alexandra L. , Oxtoby Neil P. , Ferreira Daniel , Mårtensson Gustav , Westman Eric , Alexander Daniel C. , Frisoni Giovanni B. , Redolfi Alberto ,   for Alzheimer’s Disease Neuroimaging Initiative and EuroPOND Consortium
Published: May 2021

Alzheimer’s disease (AD) is a neurodegenerative disorder which spans several years from preclinical manifestations to dementia. In recent years, interest in the application of machine learning (ML) algorithms to personalized medicine has grown considerably, and a major challenge that such models face is the transferability from the research settings to clinical practice. The objective of this work was to demonstrate the transferability of the Subtype and Stage Inference (SuStaIn) model from well-characterized research data set, employed as training set, to independent less-structured and heterogeneous test sets representative of the clinical setting. The training set was composed of MRI data of 1043 subjects from the Alzheimer’s disease Neuroimaging Initiative (ADNI), and the test set was composed of data from 767 subjects from OASIS, Pharma-Cog, and ViTA clinical datasets. Both sets included subjects covering the entire spectrum of AD, and for both sets volumes of relevant brain regions were derived from T1-3D MRI scans processed with Freesurfer v5.3 cross-sectional stream. In order to assess the predictive value of the model, subpopulations of subjects with stable mild cognitive impairment (MCI) and MCIs that progressed to AD dementia (pMCI) were identified in both sets. SuStaIn identified three disease subtypes, of which the most prevalent corresponded to the typical atrophy pattern of AD. The other SuStaIn subtypes exhibited similarities with the previously defined hippocampal sparing and limbic predominant atrophy patterns of AD. Subject subtyping proved to be consistent in time for all cohorts and the staging provided by the model was correlated with cognitive performance. Classification of subjects on the basis of a combination of SuStaIn subtype and stage, mini mental state examination and amyloid-β1-42 cerebrospinal fluid concentration was proven to predict conversion from MCI to AD dementia on par with other novel statistical algorithms, with ROC curves that were not statistically different for the training and test sets and with area under curve respectively equal to 0.77 and 0.76. This study proves the transferability of a SuStaIn model for AD from research data to less-structured clinical cohorts, and indicates transferability to the clinical setting.
The Advent of COVID-19; Periodontal Research Has Identified Therapeutic Targets for Severe Respiratory Disease; an Example of Parallel Biomedical Research Agendas
Authors: Cardoso Elaine O. C. , Fine Noah , Glogauer Michael , Johnson Francis , Goldberg Michael , Golub Lorne M. , Tenenbaum Howard C.
Published: May 2021

The pathophysiology of SARS-CoV-2 infection is characterized by rapid virus replication and aggressive inflammatory responses that can lead to acute respiratory distress syndrome (ARDS) only a few days after the onset of symptoms. It is suspected that a dysfunctional immune response is the main cause of SARS-CoV-2 infection-induced lung destruction and mortality due to massive infiltration of hyperfunctional neutrophils in these organs. Similarly, neutrophils are recruited constantly to the oral cavity to combat microorganisms in the dental biofilm and hyperfunctional neutrophil phenotypes cause destruction of periodontal tissues when periodontitis develops. Both disease models arise because of elevated host defenses against invading organisms, while concurrently causing host damage/disease when the immune cells become hyperfunctional. This represents a clear nexus between periodontal and medical research. As researchers begin to understand the link between oral and systemic diseases and their potential synergistic impact on general health, we argue that translational research from studies in periodontology must be recognized as an important source of information that might lead to different therapeutic options which can be effective for the management of both oral and non-oral diseases. In this article we connect concepts from periodontal research on oral inflammation while exploring host modulation therapy used for periodontitis as a potential strategy for the prevention of ARDS a deadly outcome of COVID-19. We suggest that host modulation therapy, although developed initially for management of periodontitis, and which inhibits proteases, cytokines, and the oxidative stress that underlie ARDS, will provide an effective and safe treatment for COVID-19.
Temporal and Spatial Variations of Soil Moisture Over Xinjiang Based on Multiple GLDAS Datasets
Authors: Hu Zengyun , Chen Xi , Li Yaoming , Zhou Qiming , Yin Gang
Published: May 2021

Under the global warming, as the typical arid region of Central Asia, the Xinjiang Uygur Autonomous Region (Xinjiang) has been experienced the remarkable warming and increased precipitation based on large previous studies. The arid and semiarid ecosystem of Xinjiang is very sensitive and vulnerable to climate change and water resource variations. However, the sparse and highly unevenly distributed in-situ stations in this region provide limited data for understanding of the soil moisture variations. In this study, the spatial and temporal changes and variations of soil moisture were explored at annual and seasonal time scales during the period of 2000–2017. The soil moisture data are from the Global Land Data Assimilation System (GLDAS) models, including four GLDAS 1 models: CLM, Mosaic, VIC and Noah 2.7 and one GLDAS 2.1 model: Noah 3.3. Major results show that 1) Noah 3.3 and VIC have the significant positive trends of annual soil moisture with the values of 2.64°mm/a and 0.98°mm/a. The trend of CLM is significant negative. The other two models Mosaic and Noah 2.7 have the weak positive trends. The temporal variations of seasonal soil moisutre are similar the annual soil moisture for each of the model. 2) For the spatial characteristics of the soil mositure variations, CLM displays the negative trends over large part of Xinjiang. Mosaic and VIC have the similar spatial characteristics of the linear trends. Noah 3.3 has the significant positive trends over almost Xinjiang which is different with Noah 2.7. All the five models have the positive trends over KLM. Our results have a better understanding of the soil moisture variations across Xinjiang, and they also enhance the reconginzing of the complex hydrological circulation in the arid regions.
Effect of EPA on Neonatal Pig Sertoli Cells “In Vitro”: A Possible Treatment to Help Maintain Fertility in Pre-Pubertal Boys Undergoing Treatment With Gonado-Toxic Therapies
Authors: Arato Iva , Ceccarelli Veronica , Mancuso Francesca , Bellucci Catia , Lilli Cinzia , Ferolla Piero , Perruccio Katia , D’Arpino Alessandro , Aglietti Maria Chiara , Calafiore Riccardo , Cameron Don F. , Calvitti Mario , Baroni Tiziano , Vecchini Alba , Luca Giovanni
Published: May 2021

The incidence of cancer in pre-pubertal boys has significantly increased and, it has been recognized that the gonado-toxic effect of the cancer treatments may lead to infertility. Here, we have evaluated the effects on porcine neonatal Sertoli cells (SCs) of three commonly used chemotherapy drugs; cisplatin, 4-Hydroperoxycyclophosphamide and doxorubicin. All three drugs induced a statistical reduction of 5-hydroxymethylcytosine in comparison with the control group, performed by Immunofluorescence Analysis. The gene and protein expression levels of GDNF, were significantly down-regulated after treatment to all three chemotherapy drugs comparison with the control group. Specifically, differences in the mRNA levels of GDNF were: 0,8200 ± 0,0440, 0,6400 ± 0,0140, 0,4400 ± 0,0130 fold change at 0.33, 1.66, and 3.33μM cisplatin concentrations, respectively (**p < 0.01 at 0.33 and 1.66 μM vs SCs and ***p < 0.001 at 3.33μM vs SCs); 0,6000 ± 0,0340, 0,4200 ± 0,0130 fold change at 50 and 100 μM of 4-Hydroperoxycyclophosphamide concentrations, respectively (**p < 0.01 at both these concentrations vs SCs); 0,7000 ± 0,0340, 0,6200 ± 0,0240, 0,4000 ± 0,0230 fold change at 0.1, 0.2 and 1 µM doxorubicin concentrations, respectively (**p < 0.01 at 0.1 and 0.2 μM vs SCs and ***p < 0.001 at 1 μM vs SCs). Differences in the protein expression levels of GDNF were: 0,7400 ± 0,0340, 0,2000 ± 0,0240, 0,0400 ± 0,0230 A.U. at 0.33, 1.66, and 3.33μM cisplatin concentrations, respectively (**p < 0.01 at both these concentrations vs SCs); 0,7300 ± 0,0340, 0,4000 ± 0,0130 A.U. at 50 and 100 μM of 4- Hydroperoxycyclophosphamide concentrations, respectively (**p < 0.01 at both these concentrations vs SCs); 0,6200 ± 0,0340, 0,4000 ± 0,0240, 0,3800 ± 0,0230 A.U. at 0.l, 0.2 and 1 µM doxorubicin concentrations, respectively (**p < 0.01 at 0.1 and 0.2 μM vs SCs and ***p < 0.001 at 1 μM vs SCs). Furthermore, we have demonstrated the protective effect of eicosapentaenoic acid on SCs only at the highest concentration of cisplatin, resulting in an increase in both gene and protein expression levels of GDNF (1,3400 ± 0,0280 fold change; **p < 0.01 vs SCs); and of AMH and inhibin B that were significantly recovered with values comparable to the control group. Results from this study, offers the opportunity to develop future therapeutic strategies for male fertility management, especially in pre-pubertal boys.
Investigation of the Techno-Economical Feasibility of the Power-to-Methane Process Based on Molten Carbonate Electrolyzer
Authors: Monzer Dayan , Rivera-Tinoco Rodrigo , Bouallou Chakib
Published: May 2021

High-temperature steam/CO2 electrolysis process has been the scope of study for the last decades. This study confers a feasible and environmental approach to convert low-carbon electrical energy into chemical energy, stored in the form of synthetic gas (H2 and CO) to be further processed in line with the final use target. It focuses on the Power-to-Methane technology using a high-temperature molten carbonates electrolyzer (MCEC). A large-scale process composed of the built-in MCEC model and the Balance of Plant (BOP) equipment is proposed and simulated with AspenPLUS software, taking into consideration the possible heat integration in the system for saving energy consumption. The proposed full-based process system shows an overall efficiency of 72%. The employment of this carbon neutral process relies on its economic competitiveness. For this reason, an economic assessment is conducted to investigate the economic feasibility of the proposed process. Indeed, the current methane production cost resulting from this process is not as competitive as market prices induced by other technologies. However, a parametric study demonstrating the impact factors on the methane selling price reveals that amelioration in the lifespan of the electrolyzer, accompanied by a reduction in its cost, can be an attractive solution, given the current market technology. This overall analysis sheds light on the role of the proposed process as an environmental-friendly and cost feasible solution for synthetic methane production.
Growth, Chemistry, and Genetic Profiles of Whitebark Pine Forests Affected by Climate-Driven Mountain Pine Beetle Outbreaks
Authors: Six Diana L. , Trowbridge Amy , Howe Michael , Perkins Dana , Berglund Erika , Brown Peter , Hicke Jeffrey A. , Balasubramanian Ganesh
Published: May 2021

Climate change-driven Dendroctonus ponderosae outbreaks in semi-naïve Pinus albicaulis may result in rapid natural selection for trees with genotypes and phenotypes associated with survival. In this study, we investigated whether survivors were genetically and chemically different from a living cohort of trees that escaped predation due to smaller size and estimated genetic diversity. We also examined how growth rate and climate sensitivity varied between beetle-killed and surviving trees. Dendroctonus ponderosae predominantly kills large diameter trees; therefore, we predicted that large surviving trees would have distinctive genetic profiles and, due to bottlenecking and drift, survivors would have lower genetic diversity than the abundant smaller mature trees that escaped predation. We found survivors were indeed genetically divergent from the smaller trees but, contrary to expectations, the smaller trees had lower diversity. This suggests that while beetles may select for trees with particular genotypes, other factors are also driving population genetic sub-structuring. Individual tree terpene profiles were diverse and varied by population but showed no clear relationship to survivorship. Two groups of trees with divergent sensitivities to climate were observed in each population, but neither was a clear indicator of survivorship or susceptibility to beetle attack. Growth rate was the best predictor of survivorship with survivors growing significantly slower than beetle-killed trees over their lifetimes although growth rates converged in years just prior to increased beetle activity. Overall, our results suggest that P. albicaulis forests show considerable divergence among populations and within-population genetic sub-structuring, and that they may contain complex mosaics of adaptive potentials to a variety of stressors including D. ponderosae. To protect the ability of this tree to adapt to increasing pressure from beetles, blister rust, and climate change, a top priority should be the maintenance of standing genetic diversity and adaptive shifts in allele frequencies.
The Impact of SARS-COVID-19 Outbreak on European Cities Urban Mobility
Authors: Vitello Piergiorgio , Fiandrino Claudio , Capponi Andrea , Klopp Pol , Connors Richard D. , Viti Francesco
Published: May 2021

The global outbreak of the SARS-COVID-19 pandemic has changed our lives, driving an unprecedented transformation of our habits. In response, the authorities have enforced several measures, including social distancing and travel restrictions that lead to thetemporaryclosure of activities centered around schools, companies, local businesses to those pertaining to the recreation category. As such, with a mobility reduction, the life of our cities during the outbreak changed significantly. In this paper, we aim at drawing attention to this problem and perform an analysis for multiple cities through crowdsensed information available from datasets such as Apple Maps, to shed light on the changes undergone during both the outbreak and the recovery. Specifically, we exploit data characterizing many mobility modes like driving, walking, and transit. With the use of Gaussian Processes and clustering techniques, we uncover patterns of similarity between the major European cities. Further, we perform a prediction analysis that permits forecasting the trend of the recovery process and exposes the deviation of each city from the trend of the cluster. Our results unveil that clusters are not typically formed by cities with geographical ties, but rather on the spread of the infection, lockdown measures, and citizens’ reactions.
Guideline-Adherent Clinical Validation of a Comprehensive 170-Gene DNA/RNA Panel for Determination of Small Variants, Copy Number Variations, Splice Variants, and Fusions on a Next-Generation Sequencing Platform in the CLIA Setting
Authors: Boyle Theresa A. , Mondal Ashis K. , Saeed-Vafa Daryoush , Ananth Sudha , Ahluwalia Pankaj , Kothapalli Ravi , Chaubey Alka , Roberts Evans , Qin Dahui , Magliocco Anthony M. , Rojiani Amyn M. , Kolhe Ravindra
Published: May 2021

We describe the clinical validation of a targeted DNA and RNA-based next-generation sequencing (NGS) assay at two clinical molecular diagnostic laboratories. This assay employs simultaneous DNA and RNA analysis of all coding exons to detect small variants (single-nucleotide variants, insertions, and deletions) in 148 genes, amplifications in 59 genes, and fusions and splice variants in 55 genes. During independent validations at two sites, 234 individual specimens were tested, including clinical formalin-fixed, paraffin-embedded (FFPE) tumor specimens, reference material, and cell lines. Samples were prepared using the Illumina TruSight Tumor 170 (TST170) kit, sequenced with Illumina sequencers, and the data were analyzed using the TST170 App. At both sites, TST170 had ≥98% success for ≥250× depth for ≥95% of covered positions. Variant calling was accurate and reproducible at allele frequencies ≥5%. Limit of detection studies determined that inputs of ≥50 ng of DNA (with ≥3.3 ng/μl) and ≥50 ng RNA (minimum of 7 copies/ng) were optimal for high analytical sensitivity. The TST170 assay results were highly concordant with prior results using different methods across all variant categories. Optimization of nucleic acid extraction and DNA shearing, and quality control following library preparation is recommended to maximize assay success rates. In summary, we describe the validation of comprehensive and simultaneous DNA and RNA-based NGS testing using TST170 at two clinical sites.
From Disease Description and Gene Discovery to Functional Cell Pathway: A Decade-Long Journey for TMCO1
Authors: Batchelor-Regan Helen , Xin Baozhong , Zhou Aimin , Wang Heng
Published: May 2021

A decade has passed since transmembrane coiled-coil domains 1 (TMCO1) defect syndrome was identified in 11 undiagnosed patients within the Old Order Amish of Northeastern Ohio—a disorder characterized by a distinctive craniofacial dysmorphism, skeletal anomalies and global developmental delay. Twenty seven patients, from diverse ethnic groups, have been reported with pathogenic TMCO1 variants now recognized to cause cerebrofaciothoracic dysplasia (CFTD). The implication of previously uncharacterized TMCO1 within disease has instigated a 10-year journey to understand the function of TMCO1 protein in Ca2+ homeostasis. TMCO1 is an ER Ca2+ leak channel which facilitates Ca2+ leak upon ER “overload” through the novel Ca2+ load activated Ca2+ mechanism. This mini-review brings together the clinical and scientific advances made since the discovery of TMCO1 deficiency in disease, including broadened phenotype, understanding of pathophysiology, and implications to patient management of TMCO1 defect syndrome.
Genome-Wide Detection of Copy Number Variations and Their Association With Distinct Phenotypes in the World’s Sheep
Authors: Salehian-Dehkordi Hosein , Xu Ya-Xi , Xu Song-Song , Li Xin , Luo Ling-Yun , Liu Ya-Jing , Wang Dong-Feng , Cao Yin-Hong , Shen Min , Gao Lei , Chen Ze-Hui , Glessner Joseph T. , Lenstra Johannes A. , Esmailizadeh Ali , Li Meng-Hua , Lv Feng-Hua
Published: May 2021

Copy number variations (CNVs) are a major source of structural variation in mammalian genomes. Here, we characterized the genome-wide CNV in 2059 sheep from 67 populations all over the world using the Ovine Infinium HD (600K) SNP BeadChip. We tested their associations with distinct phenotypic traits by conducting multiple independent genome-wide tests. In total, we detected 7547 unique CNVs and 18,152 CNV events in 1217 non-redundant CNV regions (CNVRs), covering 245 Mb (∼10%) of the whole sheep genome. We identified seven CNVRs with frequencies correlating to geographical origins and 107 CNVRs overlapping 53 known quantitative trait loci (QTLs). Gene ontology and pathway enrichment analyses of CNV-overlapping genes revealed their common involvement in energy metabolism, endocrine regulation, nervous system development, cell proliferation, immune, and reproduction. For the phenotypic traits, we detected significantly associated (adjusted P < 0.05) CNVRs harboring functional candidate genes, such as SBNO2 for polycerate; PPP1R11 and GABBR1 for tail weight; AKT1 for supernumerary nipple; CSRP1, WNT7B, HMX1, and FGFR3 for ear size; and NOS3 and FILIP1 in Wadi sheep; SNRPD3, KHDRBS2, and SDCCAG3 in Hu sheep; NOS3, BMP1, and SLC19A1 in Icelandic; CDK2 in Finnsheep; MICA in Romanov; and REEP4 in Texel sheep for litter size. These CNVs and associated genes are important markers for molecular breeding of sheep and other livestock species.
Mitf Involved in Innate Immunity by Activating Tyrosinase-Mediated Melanin Synthesis in Pteria penguin
Authors: Yu Feifei , Lu Yishan , Zhong Zhiming , Qu Bingliang , Wang Meifang , Yu Xiangyong , Chen Jiayu
Published: May 2021

The microphthalmia-associated transcription factor (MITF) is an important transcription factor that plays a key role in melanogenesis, cell proliferation, survival and immune defense in vertebrate. However, its function and function mechanism in bivalve are still rarely known. In this research, first, a Mitf gene was characterized from Pteria penguin (P. penguin). The PpMitf contained an open reading frame of 1,350 bp, encoding a peptide of 449 deduced amino acids with a highly conserved basic helix-loop-helix-leucine zipper (bHLH-LZ) domain. The PpMITF shared 55.7% identity with amino acid sequence of Crassostrea gigas (C. gigas). Tissue distribution analysis revealed that PpMitf was highly expressed in mantle and hemocytes, which were important tissues for color formation and innate immunity. Second, the functions of PpMitf in melanin synthesis and innate immunity were identified. The PpMitf silencing significantly decreased the tyrosinase activity and melanin content, indicating PpMitf involved in melanin synthesis of P. penguin. Meanwhile, the PpMitf silencing clearly down-regulated the expression of PpBcl2 (B cell lymphoma/leukemia-2 gene) and antibacterial activity of hemolymph supernatant, indicating that PpMitf involved in innate immunity of P. penguin. Third, the function mechanism of PpMitf in immunity was analyzed. The promoter sequence analysis of tyrosinase (Tyr) revealed two highly conserved E-box elements, which were specifically recognized by HLH-LZ of MITF. The luciferase activities analysis showed that Mitf could activate the E-box in Tyr promoter through highly conserved bHLH-LZ domain, and demonstrated that PpMitf involved in melanin synthesis and innate immunity by regulating tyrosinase expression. Finally, melanin from P. penguin, the final production of Mitf-Tyr-melanin pathway, was confirmed to have direct antibacterial activity. The results collectively demonstrated that PpMitf played a key role in innate immunity through activating tyrosinase-mediated melanin synthesis in P. penguin.
Procalcitonin and Interleukin-10 May Assist in Early Prediction of Bacteraemia in Children With Cancer and Febrile Neutropenia
Authors: Doerflinger Marcel , Haeusler Gabrielle M. , Li-Wai-Suen Connie S. N. , Clark Julia E. , Slavin Monica , Babl Franz E. , Allaway Zoe , Mechinaud Francoise , Smyth Gordon K. , De Abreu Lourenco Richard , Phillips Bob , Pellegrini Marc , Thursky Karin A.
Published: May 2021

Objectives

Febrile neutropenia (FN) causes treatment disruption and unplanned hospitalization in children with cancer. Serum biomarkers are infrequently used to stratify these patients into high or low risk for serious infection. This study investigated plasma abundance of cytokines in children with FN and their ability to predict bacteraemia.

Methods

Thirty-three plasma cytokines, C-reactive protein (CRP) and procalcitonin (PCT) were measured using ELISA assays in samples taken at FN presentation (n = 79) and within 8–24 h (Day 2; n = 31). Optimal thresholds for prediction of bacteraemia were identified and the predictive ability of biomarkers in addition to routinely available clinical variables was assessed.

Results

The median age of included FN episodes was 6.0 years and eight (10%) had a bacteraemia. On presentation, elevated PCT, IL-10 and Mip1-beta were significantly associated with bacteraemia, while CRP, IL-6 and IL-8 were not. The combination of PCT (≥0.425 ng/ml) and IL-10 (≥4.37 pg/ml) had a sensitivity of 100% (95% CI 68.8–100%) and specificity of 89% (95% CI 80.0–95.0%) for prediction of bacteraemia, correctly identifying all eight bacteraemia episodes and classifying 16 FN episodes as high-risk. There was limited additive benefit of incorporating clinical variables to this model. On Day 2, there was an 11-fold increase in PCT in episodes with a bacteraemia which was significantly higher than that observed in the non-bacteraemia episodes.

Conclusion

Elevated PCT and IL-10 accurately identified all bacteraemia episodes in our FN cohort and may enhance the early risk stratification process in this population. Prospective validation and implementation is required to determine the impact on health service utilisation.
Tumor Necrosis Factor Inhibitors Exacerbate Whipple’s Disease by Reprogramming Macrophage and Inducing Apoptosis
Authors: Boumaza Asma , Mezouar Soraya , Bardou Matthieu , Raoult Didier , Mège Jean-Louis , Desnues Benoit
Published: May 2021

Tropheryma whippleiis the agent of Whipple’s disease, a rare systemic disease characterized by macrophage infiltration of the intestinal mucosa. The disease first manifests as arthralgia and/or arthropathy that usually precede the diagnosis by years, and which may push clinicians to prescribe Tumor necrosis factor inhibitors (TNFI) to treat unexplained arthralgia. However, such therapies have been associated with exacerbation of subclinical undiagnosed Whipple’s disease. The objective of this study was to delineate the biological basis of disease exacerbation. We found that etanercept, adalimumab or certolizumab treatment of monocyte-derived macrophages from healthy subjects significantly increased bacterial replicationin vitrowithout affecting uptake. Interestingly, this effect was associated with macrophage repolarization and increased rate of apoptosis. Further analysis revealed that in patients for whom Whipple’s disease diagnosis was made while under TNFI therapy, apoptosis was increased in duodenal tissue specimens as compared with control Whipple’s disease patients who never received TNFI prior diagnosis. In addition, IFN-γ expression was increased in duodenal biopsy specimen and circulating levels of IFN-γ were higher in patients for whom Whipple’s disease diagnosis was made while under TNFI therapy. Taken together, our findings establish that TNFI aggravate/exacerbate latent or subclinical undiagnosed Whipple’s disease by promoting a strong inflammatory response and apoptosis and confirm that patients may be screened forT. whippleiprior to introduction of TNFI therapy.
LECT2 Protects Nile Tilapia (Oreochromis niloticus) Against Streptococcus agalatiae Infection
Authors: Li Qi , Zhang Zhiqiang , Fan Weiqi , Huang Yongxiong , Niu Jinzhong , Luo Guoling , Liu Xinchao , Huang Yu , Jian Jichang
Published: May 2021

Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine that especially plays an important role in innate immune. However, the roles of LECT2 in the immune response of the economically important fish Nile tilapia (Oreochromis niloticus) against bacterial infection remains unclear. In this study, a lect2 gene from Nile tilapia (On-lect2) was identified, and its roles in the fish’s immune response against bacterial infection were determined and characterised. On-lect2 contains an open reading frame of 456 bp that encodes a peptide of 151 amino acids, as well as the conservative peptidase M23 domain. On-LECT2 is 62%–84% identical to other fish species and about 50% identical to mammals. The highest transcriptional level of On-lect2 was detected in the liver, whereas the lowest levels were detected in the other tissues. Moreover, the On-LECT2 protein is located mainly in the brain and head kidney. The transcriptional levels of On-lect2 substantially increased in the head kidney, brain, liver and spleen after Streptococcus agalactiae infection. Knockdown On-lect2 led to higher mortality due to liver necrosis or haemorrhage and splenomegaly. In vitro analysis indicated that the recombinant protein of On-LECT2 improved phagocytic activity of head kidney-derived macrophages. In vivo challenge experiments revealed several functions of On-LECT2 in the immune response of Nile tilapia against bacterial infection, including promotion of inflammation, reduction of tissue damages and improvement of survival rate.
Sponges With Microbial Symbionts Transform Dissolved Organic Matter and Take Up Organohalides
Authors: Olinger Lauren K. , Strangman Wendy K. , McMurray Steven E. , Pawlik Joseph R.
Published: May 2021

Seawater dissolved organic matter (DOM) is a large reservoir of carbon composed of a complex and poorly characterized mixture of molecules. Sponges have long been known to consume dissolved organic carbon (DOC) from this mixture, but the role of microbial sponge symbionts in this process is complex, and the molecules involved remain largely unknown. In order to better understand how sponge processing changes seawater DOM, we used untargeted metabolomics to characterize DOM in samples of incurrent and excurrent seawater taken from sponges on the fore-reef off Carrie Bow Cay, Belize, over 2 years. We collected samples from three sponge species each with either high or low microbial abundance (HMA, LMA) to explore the relationship between symbiont abundance and DOM alterations. Analyses revealed that sponges took up metabolites and changed the composition of seawater DOM, but only for the three HMA species, and none of the LMA species, implicating microbial symbionts in this uptake. Using a new mass spectra classification tool, we found that putative compositions of features depleted in the excurrent samples of HMA sponges were similar in both years and were dominated by organic acids and derivatives (74%) and organic nitrogen compounds (19%). Interestingly, HMA sponges also took up halogenated compounds (containing chlorine or bromine), providing evidence of a previously unknown mechanism of halide cycling. The metabolites taken up by HMA sponges may be used as a food source or as building blocks of chemical defenses, selective advantages that may have guided the evolution of microbial symbioses in sponges.
A State-of-the-Art Review of Marine Ecosystem Services in the Rías Baixas Natura 2000 Network (Galicia, NW Spain)
Authors: Tubío Ana , Pita Pablo , Barañano Carlota , Villasante Sebastián
Published: May 2021

Humans are deeply connected to the oceans, who provide us vital ecosystem services (ES) (climate regulation, control of natural threats, wealth of its biodiversity, etc.), but the oceans are the first to suffer from human activity (climate change, destruction of ecosystems, overexploitation of marine resources, pollution, endangered species, etc.). Marine biodiversity is a fundamental natural capital in the generation of marine ecosystem services (MES), fundamental elements for the maintenance of human wellbeing. The objective of this article is to empirically demonstrate the role of marine ES in natural protected areas in Nature 2000 Rías Baixas (N2RB) (Galicia, NW Spain) in order to (1) to improve the knowledge on natural capital and ES associated to conserved coastal areas, (2) to analyze the contribution of these conserved coastal areas to the provision of sustainable business opportunities, and (3) to analyze if green-oriented policies can revert the current unsustainable exploitation model by providing real opportunities for business development. By creating an inventory, we gathered detailed information collected up to October 2020 of scientific literature, research projects, press releases, information on business initiatives and public policies regulations on ES and conservation of marine biodiversity in the N2RB (Cíes Islands and Island of Ons, including the Ons–O Grove Complex). Better protection of marine natural capital needs coordinated efforts among all sectors of government, business, and international institutions. It is a priority to generate a greater degree of social and business commitment that promotes the conservation of marine biodiversity, through the design of social and business participation strategies in the planning and use of ES in the N2RB areas.
Isolation and Analysis of Donor Chromosomal Genes Whose Deficiency Is Responsible for Accelerating Bacterial and Trans-Kingdom Conjugations by IncP1 T4SS Machinery
Authors: Zoolkefli Fatin Iffah Rasyiqah Mohamad , Moriguchi Kazuki , Cho Yunjae , Kiyokawa Kazuya , Yamamoto Shinji , Suzuki Katsunori
Published: May 2021

Conjugal transfer is a major driving force of genetic exchange in eubacteria, and the system in IncP1-type broad-host-range plasmids transfers DNA even to eukaryotes and archaea in a process known as trans-kingdom conjugation (TKC). Although conjugation factors encoded on plasmids have been extensively analyzed, those on the donor chromosome have not. To identify the potential conjugation factor(s), a genome-wide survey on a comprehensive collection of Escherichia coli gene knockout mutants (Keio collection) as donors to Saccharomyces cerevisiae recipients was performed using a conjugal transfer system mediated by the type IV secretion system (T4SS) of the IncP1α plasmid. Out of 3,884 mutants, three mutants (ΔfrmR, ΔsufA, and ΔiscA) were isolated, which showed an increase by one order of magnitude in both E. coli–E. coli and E. coli–yeast conjugations without an increase in the mRNA accumulation level for the conjugation related genes examined. The double-knockout mutants for these genes (ΔfrmRΔsufA and ΔiscAΔfrmR) did not show synergistic effects on the conjugation efficiency, suggesting that these factors affect a common step in the conjugation machinery. The three mutants demonstrated increased conjugation efficiency in IncP1β-type but not in IncN- and IncW-type broad-host-range plasmid transfers, and the homologous gene knockout mutants against the three genes in Agrobacterium tumefaciens also showed increased TKC efficiency. These results suggest the existence of a specific regulatory system in IncP1 plasmids that enables the control of conjugation efficiency in different hosts, which could be utilized for the development of donor strains as gene introduction tools into bacteria, eukaryotes, and archaea.
Effects of Hsp90 Inhibitor Ganetespib on Inhibition of Azole-Resistant Candida albicans
Authors: Yuan Rui , Tu Jie , Sheng Chunquan , Chen Xi , Liu Na
Published: May 2021

Candida albicans is the most common fungal pathogen. Recently, drug resistance of C. albicans is increasingly severe. Hsp90 is a promising antifungal target to overcome this problem. To evaluate the effects of Hsp90 inhibitor ganetespib on the inhibition of azole-resistant C. albicans, the microdilution checkerboard method was used to measure the in vitro synergistic efficacy of ganetespib. The XTT/menadione reduction assay, microscopic observation, and Rh6G efflux assay were established to investigate the effects of ganetespib on azole-resistant C. albicans biofilm formation, filamentation, and efflux pump. Real-time RT-PCR analysis was employed to clarify the mechanism of antagonizing drug resistance. The in vivo antifungal efficacy of ganetespib was determined by the infectious model of azole-resistant C. albicans. Ganetespib showed an excellent synergistic antifungal activity in vitro and significantly inhibited the fungal biofilm formation, whereas it had no inhibitory effect on fungal hypha formation. Expression of azole-targeting enzyme gene ERG11 and efflux pump genes CDR1, CDR2, and MDR1 was significantly down-regulated when ganetespib was used in combination with FLC. In a mouse model infected with FLC-resistant C. albicans, the combination of ganetespib and FLC effectively reversed the FLC resistance and significantly decreased the kidney fungal load of mouse.
Carbon-Source Dependent Interplay of Copper and Manganese Ions Modulates the Morphology and Itaconic Acid Production in Aspergillus terreus
Authors: Sándor Erzsébet , Kolláth István S. , Fekete Erzsébet , Bíró Vivien , Flipphi Michel , Kovács Béla , Kubicek Christian P. , Karaffa Levente
Published: May 2021

The effects of the interplay of copper(II) and manganese(II) ions on growth, morphology and itaconic acid formation was investigated in a high-producing strain of Aspergillus terreus (NRRL1960), using carbon sources metabolized either mainly via glycolysis (D-glucose, D-fructose) or primarily via the pentose phosphate shunt (D-xylose, L-arabinose). Limiting Mn2+ concentration in the culture broth is indispensable to obtain high itaconic acid yields, while in the presence of higher Mn2+ concentrations yield decreases and biomass formation is favored. However, this low yield in the presence of high Mn2+ ion concentrations can be mitigated by increasing the Cu2+ concentration in the medium when D-glucose or D-fructose is the growth substrate, whereas this effect was at best modest during growth on D-xylose or L-arabinose. A. terreus displays a high tolerance to Cu2+ which decreased when Mn2+ availability became increasingly limiting. Under such conditions biomass formation on D-glucose or D-fructose could be sustained at concentrations up to 250 mg L–1 Cu2+, while on D-xylose- or L-arabinose biomass formation was completely inhibited at 100 mg L–1. High (>75%) specific molar itaconic acid yields always coincided with an “overflow-associated” morphology, characterized by small compact pellets (<250 μm diameter) and short chains of “yeast-like” cells that exhibit increased diameters relative to the elongated cells in growing filamentous hyphae. At low concentrations (≤1 mg L–1) of Cu2+ ions, manganese deficiency did not prevent filamentous growth. Mycelial- and cellular morphology progressively transformed into the typical overflow-associated one when external Cu2+ concentrations increased, irrespective of the available Mn2+. Our results indicate that copper ions are relevant for overflow metabolism and should be considered when optimizing itaconic acid fermentation in A. terreus.
Navigating Hereditary Hearing Loss: Pathology of the Inner Ear
Authors: Nicolson Teresa
Published: May 2021

Inherited forms of deafness account for a sizable portion of hearing loss among children and adult populations. Many patients with sensorineural deficits have pathological manifestations in the peripheral auditory system, the inner ear. Within the hearing organ, the cochlea, most of the genetic forms of hearing loss involve defects in sensory detection and to some extent, signaling to the brain via the auditory cranial nerve. This review focuses on peripheral forms of hereditary hearing loss and how these impairments can be studied in diverse animal models or patient-derived cells with the ultimate goal of using the knowledge gained to understand the underlying biology and treat hearing loss.