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Article ; Online: Intervertebral disc-on-a-chip: a precision engineered toolbox for low back pain studies.

Tavakoli, Javad / Diwan, Ashish D / Tipper, Joanne L

2023 Volume 41, Issue 11, Page(s) 1339–1342

Abstract: Current in vitro intervertebral disc (IVD) models do not fully recapitulate the complex mechanobiology of native tissue, and so far there is no strategy to effectively evaluate IVD regeneration. The development of a modular microfluidic on-chip model is ... ...

Abstract	Current in vitro intervertebral disc (IVD) models do not fully recapitulate the complex mechanobiology of native tissue, and so far there is no strategy to effectively evaluate IVD regeneration. The development of a modular microfluidic on-chip model is expected to enhance the physiological relevance of experimental data leading to successful clinical outcomes.
Language	English
Publishing date	2023-05-13
Publishing country	England
Document type	Journal Article
ZDB-ID	47474-5
ISSN	1879-3096 ; 0167-7799
ISSN (online)	1879-3096
ISSN	0167-7799
DOI	10.1016/j.tibtech.2023.04.009
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Article ; Online: Advanced Strategies for the Regeneration of Lumbar Disc Annulus Fibrosus.

Tavakoli, Javad / Diwan, Ashish D / Tipper, Joanne L

International journal of molecular sciences

2020 Volume 21, Issue 14

Abstract: Damage to the annulus fibrosus (AF), the outer region of the intervertebral disc (IVD), results in an undesirable condition that may accelerate IVD degeneration causing low back pain. Despite intense research interest, attempts to regenerate the IVD have ...

Abstract	Damage to the annulus fibrosus (AF), the outer region of the intervertebral disc (IVD), results in an undesirable condition that may accelerate IVD degeneration causing low back pain. Despite intense research interest, attempts to regenerate the IVD have failed so far and no effective strategy has translated into a successful clinical outcome. Of particular significance, the failure of strategies to repair the AF has been a major drawback in the regeneration of IVD and nucleus replacement. It is unlikely to secure regenerative mediators (cells, genes, and biomolecules) and artificial nucleus materials after injection with an unsealed AF, as IVD is exposed to significant load and large deformation during daily activities. The AF defects strongly change the mechanical properties of the IVD and activate catabolic routes that are responsible for accelerating IVD degeneration. Therefore, there is a strong need to develop effective therapeutic strategies to prevent or reconstruct AF damage to support operational IVD regenerative strategies and nucleus replacement. By the way of this review, repair and regenerative strategies for AF reconstruction, their current status, challenges ahead, and future outlooks were discussed.
MeSH term(s)	Animals ; Annulus Fibrosus/physiology ; Annulus Fibrosus/physiopathology ; Humans ; Intervertebral Disc/physiopathology ; Intervertebral Disc Degeneration/physiopathology ; Lumbosacral Region/physiopathology ; Regeneration/physiology
Language	English
Publishing date	2020-07-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21144889
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Article ; Online: The ultrastructural organization of elastic fibers at the interface of the nucleus and annulus of the intervertebral disk.

Tavakoli, Javad / Diwan, Ashish D / Tipper, Joanne L

Acta biomaterialia

2020 Volume 114, Page(s) 323–332

Abstract: There has been no study to describe the ultrastructural organization of elastic fibers at the interface of the nucleus pulposus and annulus fibrosus of the intervertebral disk (IVD), a region called the transition zone (TZ). A previously developed ... ...

Abstract	There has been no study to describe the ultrastructural organization of elastic fibers at the interface of the nucleus pulposus and annulus fibrosus of the intervertebral disk (IVD), a region called the transition zone (TZ). A previously developed digestion technique was optimized to eliminate cells and non-elastin ECM components except for the elastic fibers from the anterolateral (AL) and posterolateral (PL) regions of the TZ in ovine IVDs. Not previously reported, the current study identified a complex elastic fiber network across the TZ for both AL and PL regions. In the AL region, this network consisted of major thick elastic fibers (≈ 1 µm) that were interconnected with delicate (< 200 nm) elastic fibers. While the same ultrastructural organization was observed in the PL region, interestingly the size of the elastic fibers was smaller (< 100 nm) compared to those that were located in the AL region. Quantitative analysis of the elastic fibers revealed significant differences in the size (p < 0.001) and the orientation of elastic fibers (p = 0.001) between the AL and PL regions, with a higher orientation and larger size of elastic fibers observed in the AL region. The gradual elimination of cells and non-elastin extracellular matrix components identified that elastic fibers in the TZ region in combination with the extracellular matrix created a honeycomb structure that was more compact at the AF interface compared to that located close to the NP. Three different symmetrically organized angles of rotation (0⁰ and ±90⁰) were detected for the honeycomb structure at both interfaces, and the structure was significantly orientated at the TZ-AF compared to the TZ-NP interface (p = 0.003).
MeSH term(s)	Animals ; Annulus Fibrosus ; Elastic Tissue ; Extracellular Matrix ; Intervertebral Disc ; Nucleus Pulposus ; Sheep
Language	English
Publishing date	2020-07-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2020.07.021
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Article ; Online: Elastic fibers: The missing key to improve engineering concepts for reconstruction of the Nucleus Pulposus in the intervertebral disc.

Tavakoli, Javad / Diwan, Ashish D / Tipper, Joanne L

Acta biomaterialia

2020 Volume 113, Page(s) 407–416

Abstract: The increasing prevalence of low back pain has imposed a heavy economic burden on global healthcare systems. Intense research activities have been performed for the regeneration of the Nucleus Pulposus (NP) of the IVD; however, tissue-engineered ... ...

Abstract	The increasing prevalence of low back pain has imposed a heavy economic burden on global healthcare systems. Intense research activities have been performed for the regeneration of the Nucleus Pulposus (NP) of the IVD; however, tissue-engineered scaffolds have failed to capture the multi-scale structural hierarchy of the native tissue. The current study revealed for the first time, that elastic fibers form a network across the NP consisting of straight and thick parallel fibers that were interconnected by wavy fine fibers and strands. Both straight fibers and twisted strands were regularly merged or branched to form a fine elastic network across the NP. As a key structural feature, ultrathin (53 ± 7 nm), thin (215 ± 20 nm), and thick (890 ± 12 nm) elastic fibers were observed in the NP. While our quantitative analysis for measurement of the thickness of elastic fibers revealed no significant differences (p < 0.633), the preferential orientation of fibers was found to be significantly different (p < 0.001) across the NP. The distribution of orientation for the elastic fibers in the NP represented one major organized angle of orientation except for the central NP. We found that the distribution of elastic fibers in the central NP was different from those located in the peripheral regions representing two symmetrically organized major peaks (±45⁰). No significant differences in the maximum fiber count at the major angles of orientation (±45⁰) were observed for both peripheral (p = 0.427) and central NP (p = 0.788). Based on these new findings a structural model for the elastic fibers in the NP was proposed. The geometrical presentation, along with the distribution of elastic fibers orientation, resulting from the present study identifies the ultrastructural organization of elastic fibers in the NP important towards understanding their mechanical role which is still under investigation. Given the results of this new geometrical analysis, more-accurate multiscale finite element models can now be developed, which will provide new insights into the mechanobiology of the IVD. In addition, the results of this study can potentially be used for the fabrication of bio-inspired tissue-engineered scaffolds and IVD models to truly capture the multi-scale structural hierarchy of IVDs. STATEMENT OF SIGNIFICANCE: Visualization of elastic fibers in the nucleus of the intervertebral disk under high magnification was not reported before. The present research utilized extracellular matrix partial digestion to address significant gaps in understanding of nucleus microstructure that can potentially be used for the fabrication of bio-inspired tissue-engineered scaffolds and disk models to truly capture the multi-scale structural hierarchy of discs.
MeSH term(s)	Elastic Tissue ; Extracellular Matrix ; Humans ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Nucleus Pulposus ; Tissue Scaffolds
Language	English
Publishing date	2020-06-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2020.06.008
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Article: Influenza A virus modulation of

D'Mello, Adonis / Lane, Jessica R / Tipper, Jennifer L / Martínez, Eriel / Roussey, Holly N / Harrod, Kevin S / Orihuela, Carlos J / Tettelin, Hervé

bioRxiv : the preprint server for biology

2023

Abstract: Background: Streptococcus pneumoniae: Methods: We investigated the pneumococcal (serotype 19F, strain EF3030) and host transcriptomes with and without influenza A virus (A/California/07 2009 pH1N1) infection at this transition. This was done using ... ...

Abstract	Background: Streptococcus pneumoniae Methods: We investigated the pneumococcal (serotype 19F, strain EF3030) and host transcriptomes with and without influenza A virus (A/California/07 2009 pH1N1) infection at this transition. This was done using primary, differentiated Human Bronchial Epithelial Cells (nHBEC) in a transwell monolayer model at an Air-Liquid Interface (ALI), with multispecies deep RNA-seq. Results: Distinct pneumococcal gene expression profiles were observed in the presence and absence of influenza. Influenza coinfection allowed for significantly greater pneumococcal growth and triggered the differential expression of bacterial genes corresponding to multiple metabolic pathways; in totality suggesting a fundamentally altered bacterial metabolic state and greater nutrient availability when coinfecting with influenza. Surprisingly, nHBEC transcriptomes were only modestly perturbed by infection with EF3030 alone in comparison to that resulting from Influenza A infection or coinfection, which had drastic alterations in thousands of genes. Influenza infected host transcriptomes suggest significant loss of ciliary function in host nHBEC cells. Conclusions: Influenza A virus infection of nHBEC promotes pneumococcal infection. One reason for this is an altered metabolic state by the bacterium, presumably due to host components made available as result of viral infection. Influenza infection had a far greater impact on the host response than did bacterial infection alone, and this included down regulation of genes involved in expressing cilia. We conclude that influenza infection promotes a pneumococcal metabolic shift allowing for transition from colonization to disseminated disease.
Language	English
Publishing date	2023-01-30
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.29.526157
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Article: A bibliometric review of peripartum cardiomyopathy compared to other cardiomyopathies using artificial intelligence and machine learning.

Grosser, M / Lin, H / Wu, M / Zhang, Y / Tipper, S / Venter, D / Lu, J / Dos Remedios, C G

Biophysical reviews

2022 Volume 14, Issue 1, Page(s) 381–401

Abstract: As developments in artificial intelligence and machine learning become more widespread in healthcare, their potential to transform clinical outcomes also increases. Peripartum cardiomyopathy is a rare and poorly-characterised condition that presents as ... ...

Abstract	As developments in artificial intelligence and machine learning become more widespread in healthcare, their potential to transform clinical outcomes also increases. Peripartum cardiomyopathy is a rare and poorly-characterised condition that presents as heart failure in the last trimester prior to delivery or within 5-6 months postpartum. The lack of a definitive understanding of the molecular causes and clinical progress of this condition suggests that bibliometrics will be well-suited to creating new insights into this serious clinical problem. We examine similarities and differences between peripartum and its closely related familial dilated cardiomyopathy and idiopathic dilated cardiomyopathy. Using PubMed as the source of bibliometric data, we apply artificial intelligence-supported natural language processing to compare extracted data and genes association with these cardiomyopathies. Gene data were enhanced with additional metadata from third-party datasets and then analysed for their impact and specificity for peripartum cardiomyopathy. Artificial intelligence identified 14 genes that distinguished peripartum from both dilated and familial dilated cardiomyopathy. They are as follows:
Language	English
Publishing date	2022-02-09
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2486483-3
ISSN	1867-2469 ; 1867-2450
ISSN (online)	1867-2469
ISSN	1867-2450
DOI	10.1007/s12551-022-00933-x
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Article ; Online: Profiling COVID-19 Genetic Research: A Data-Driven Study Utilizing Intelligent Bibliometrics.

Wu, Mengjia / Zhang, Yi / Grosser, Mark / Tipper, Steven / Venter, Deon / Lin, Hua / Lu, Jie

Frontiers in research metrics and analytics

2021 Volume 6, Page(s) 683212

Abstract: The COVID-19 pandemic constitutes an ongoing worldwide threat to human society and has caused massive impacts on global public health, the economy and the political landscape. The key to gaining control of the disease lies in understanding the genetics ... ...

Abstract	The COVID-19 pandemic constitutes an ongoing worldwide threat to human society and has caused massive impacts on global public health, the economy and the political landscape. The key to gaining control of the disease lies in understanding the genetics of SARS-CoV-2 and the disease spectrum that follows infection. This study leverages traditional and intelligent bibliometric methods to conduct a multi-dimensional analysis on 5,632 COVID-19 genetic research papers, revealing that 1) the key players include research institutions from the United States, China, Britain and Canada; 2) research topics predominantly focus on virus infection mechanisms, virus testing, gene expression related to the immune reactions and patient clinical manifestation; 3) studies originated from the comparison of SARS-CoV-2 to previous human coronaviruses, following which research directions diverge into the analysis of virus molecular structure and genetics, the human immune response, vaccine development and gene expression related to immune responses; and 4) genes that are frequently highlighted include
Language	English
Publishing date	2021-05-24
Publishing country	Switzerland
Document type	Journal Article
ISSN	2504-0537
ISSN (online)	2504-0537
DOI	10.3389/frma.2021.683212
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Article ; Online: Elastic Fibers in the Intervertebral Disc: From Form to Function and toward Regeneration.

Cyril, Divya / Giugni, Amelia / Bangar, Saie Sunil / Mirzaeipoueinak, Melika / Shrivastav, Dipika / Sharabi, Mirit / Tipper, Joanne L / Tavakoli, Javad

International journal of molecular sciences

2022 Volume 23, Issue 16

Abstract: Despite extensive efforts over the past 40 years, there is still a significant gap in knowledge of the characteristics of elastic fibers in the intervertebral disc (IVD). More studies are required to clarify the potential contribution of elastic fibers ... ...

Abstract	Despite extensive efforts over the past 40 years, there is still a significant gap in knowledge of the characteristics of elastic fibers in the intervertebral disc (IVD). More studies are required to clarify the potential contribution of elastic fibers to the IVD (healthy and diseased) function and recommend critical areas for future investigations. On the other hand, current IVD in-vitro models are not true reflections of the complex biological IVD tissue and the role of elastic fibers has often been ignored in developing relevant tissue-engineered scaffolds and realistic computational models. This has affected the progress of IVD studies (tissue engineering solutions, biomechanics, fundamental biology) and translation into clinical practice. Motivated by the current gap, the current review paper presents a comprehensive study (from the early 1980s to 2022) that explores the current understanding of structural (multi-scale hierarchy), biological (development and aging, elastin content, and cell-fiber interaction), and biomechanical properties of the IVD elastic fibers, and provides new insights into future investigations in this domain.
MeSH term(s)	Elastic Tissue ; Humans ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Tissue Engineering ; Tissue Scaffolds/chemistry
Language	English
Publishing date	2022-08-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23168931
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Article ; Online: Influenza A-induced cystic fibrosis transmembrane conductance regulator dysfunction increases susceptibility to Streptococcus pneumoniae.

Earnhardt, Erin Y / Tipper, Jennifer L / D'Mello, Adonis / Jian, Ming-Yuan / Conway, Elijah S / Mobley, James A / Orihuela, Carlos J / Tettelin, Hervé / Harrod, Kevin S

JCI insight

2023 Volume 8, Issue 14

Abstract: Influenza A virus (IAV) infection is commonly complicated by secondary bacterial infections that lead to increased morbidity and mortality. Our recent work demonstrates that IAV disrupts airway homeostasis, leading to airway pathophysiology resembling ... ...

Abstract	Influenza A virus (IAV) infection is commonly complicated by secondary bacterial infections that lead to increased morbidity and mortality. Our recent work demonstrates that IAV disrupts airway homeostasis, leading to airway pathophysiology resembling cystic fibrosis disease through diminished cystic fibrosis transmembrane conductance regulator (CFTR) function. Here, we use human airway organotypic cultures to investigate how IAV alters the airway microenvironment to increase susceptibility to secondary infection with Streptococcus pneumoniae (Spn). We observed that IAV-induced CFTR dysfunction and airway surface liquid acidification is central to increasing susceptibility to Spn. Additionally, we observed that IAV induced profound transcriptional changes in the airway epithelium and proteomic changes in the airway surface liquid in both CFTR-dependent and -independent manners. These changes correspond to multiple diminished host defense pathways and altered airway epithelial function. Collectively, these findings highlight both the importance of CFTR function during infectious challenge and demonstrate a central role for the lung epithelium in secondary bacterial infections following IAV.
MeSH term(s)	Humans ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Streptococcus pneumoniae ; Influenza, Human/complications ; Influenza, Human/metabolism ; Proteomics ; Lung/metabolism
Chemical Substances	Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6)
Language	English
Publishing date	2023-07-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.170022
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Article ; Online: Triple oxygen isotope insight into terrestrial pyrite oxidation.

Hemingway, Jordon D / Olson, Haley / Turchyn, Alexandra V / Tipper, Edward T / Bickle, Mike J / Johnston, David T

Proceedings of the National Academy of Sciences of the United States of America

2020 Volume 117, Issue 14, Page(s) 7650–7657

Abstract: The mass-independent minor oxygen isotope compositions (Δ' ...

Abstract	The mass-independent minor oxygen isotope compositions (Δ'
Language	English
Publishing date	2020-03-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1917518117
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