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Article: Matrisome AnalyzeR: A suite of tools to annotate and quantify ECM molecules in big datasets across organisms.

Petrov, Petar B / Considine, James M / Izzi, Valerio / Naba, Alexandra

bioRxiv : the preprint server for biology

2023

Abstract: The extracellular matrix (ECM) is a complex meshwork of proteins that forms the scaffold of all tissues in multicellular organisms. It plays critical roles in all aspects of life: from orchestrating cell migration during development, to supporting tissue ...

Abstract	The extracellular matrix (ECM) is a complex meshwork of proteins that forms the scaffold of all tissues in multicellular organisms. It plays critical roles in all aspects of life: from orchestrating cell migration during development, to supporting tissue repair. It also plays critical roles in the etiology or progression of diseases. To study this compartment, we defined the compendium of all genes encoding ECM and ECM-associated proteins for multiple organisms. We termed this compendium the "matrisome" and further classified matrisome components into different structural or functional categories. This nomenclature is now largely adopted by the research community to annotate -omics datasets and has contributed to advance both fundamental and translational ECM research. Here, we report the development of Matrisome AnalyzeR, a suite of tools including a web-based application ( https://sites.google.com/uic.edu/matrisome/tools/matrisome-analyzer ) and an R package ( https://github.com/Matrisome/MatrisomeAnalyzeR ). The web application can be used by anyone interested in annotating, classifying, and tabulating matrisome molecules in large datasets without requiring programming knowledge. The companion R package is available to more experienced users, interested in processing larger datasets or in additional data visualization options. Summary statement: Matrisome AnalyzeR is a suite of tools, including a web-based app and an R package, designed to facilitate the annotation and quantification of extracellular matrix components in big datasets.
Language	English
Publishing date	2023-04-20
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.18.537378
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Article ; Online: Matrisome AnalyzeR - a suite of tools to annotate and quantify ECM molecules in big datasets across organisms.

Petrov, Petar B / Considine, James M / Izzi, Valerio / Naba, Alexandra

Journal of cell science

2023 Volume 136, Issue 17

Abstract: The extracellular matrix (ECM) is a complex meshwork of proteins that forms the scaffold of all tissues in multicellular organisms. It plays crucial roles in all aspects of life - from orchestrating cell migration during development, to supporting tissue ...

Abstract	The extracellular matrix (ECM) is a complex meshwork of proteins that forms the scaffold of all tissues in multicellular organisms. It plays crucial roles in all aspects of life - from orchestrating cell migration during development, to supporting tissue repair. It also plays critical roles in the etiology or progression of diseases. To study this compartment, we have previously defined the compendium of all genes encoding ECM and ECM-associated proteins for multiple organisms. We termed this compendium the 'matrisome' and further classified matrisome components into different structural or functional categories. This nomenclature is now largely adopted by the research community to annotate '-omics' datasets and has contributed to advance both fundamental and translational ECM research. Here, we report the development of Matrisome AnalyzeR, a suite of tools including a web-based application and an R package. The web application can be used by anyone interested in annotating, classifying and tabulating matrisome molecules in large datasets without requiring programming knowledge. The companion R package is available to more experienced users, interested in processing larger datasets or in additional data visualization options.
MeSH term(s)	Extracellular Matrix/metabolism ; Extracellular Matrix Proteins/genetics ; Extracellular Matrix Proteins/metabolism ; Cell Movement
Chemical Substances	Extracellular Matrix Proteins
Language	English
Publishing date	2023-09-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.261255
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Article ; Online: Muscle prestimulation tunes velocity preflex in simulated perturbed hopping.

Izzi, Fabio / Mo, An / Schmitt, Syn / Badri-Spröwitz, Alexander / Haeufle, Daniel F B

Scientific reports

2023 Volume 13, Issue 1, Page(s) 4559

Abstract: Muscle fibres possess unique visco-elastic properties, which generate a stabilising zero-delay response to unexpected perturbations. This instantaneous response-termed "preflex"-mitigates neuro-transmission delays, which are hazardous during fast ... ...

Abstract	Muscle fibres possess unique visco-elastic properties, which generate a stabilising zero-delay response to unexpected perturbations. This instantaneous response-termed "preflex"-mitigates neuro-transmission delays, which are hazardous during fast locomotion due to the short stance duration. While the elastic contribution to preflexes has been studied extensively, the function of fibre viscosity due to the force-velocity relation remains unknown. In this study, we present a novel approach to isolate and quantify the preflex force produced by the force-velocity relation in musculo-skeletal computer simulations. We used our approach to analyse the muscle response to ground-level perturbations in simulated vertical hopping. Our analysis focused on the preflex-phase-the first 30 ms after impact-where neuronal delays render a controlled response impossible. We found that muscle force at impact and dissipated energy increase with perturbation height, helping reject the perturbations. However, the muscle fibres reject only 15% of step-down perturbation energy with constant stimulation. An open-loop rising stimulation, observed in locomotion experiments, amplified the regulatory effects of the muscle fibre's force-velocity relation, resulting in 68% perturbation energy rejection. We conclude that open-loop neuronal tuning of muscle activity around impact allows for adequate feed-forward tuning of muscle fibre viscous capacity, facilitating energy adjustment to unexpected ground-level perturbations.
MeSH term(s)	Musculoskeletal System ; Locomotion/physiology ; Muscle Fibers, Skeletal ; Computer Simulation ; Time Factors ; Muscle Contraction/physiology ; Muscle, Skeletal/physiology
Language	English
Publishing date	2023-03-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-31179-6
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Article ; Online: Slack-based tunable damping leads to a trade-off between robustness and efficiency in legged locomotion.

Mo, An / Izzi, Fabio / Gönen, Emre Cemal / Haeufle, Daniel / Badri-Spröwitz, Alexander

Scientific reports

2023 Volume 13, Issue 1, Page(s) 3290

Abstract: Animals run robustly in diverse terrain. This locomotion robustness is puzzling because axon conduction velocity is limited to a few tens of meters per second. If reflex loops deliver sensory information with significant delays, one would expect a ... ...

Abstract	Animals run robustly in diverse terrain. This locomotion robustness is puzzling because axon conduction velocity is limited to a few tens of meters per second. If reflex loops deliver sensory information with significant delays, one would expect a destabilizing effect on sensorimotor control. Hence, an alternative explanation describes a hierarchical structure of low-level adaptive mechanics and high-level sensorimotor control to help mitigate the effects of transmission delays. Motivated by the concept of an adaptive mechanism triggering an immediate response, we developed a tunable physical damper system. Our mechanism combines a tendon with adjustable slackness connected to a physical damper. The slack damper allows adjustment of damping force, onset timing, effective stroke, and energy dissipation. We characterize the slack damper mechanism mounted to a legged robot controlled in open-loop mode. The robot hops vertically and planarly over varying terrains and perturbations. During forward hopping, slack-based damping improves faster perturbation recovery (up to 170%) at higher energetic cost (27%). The tunable slack mechanism auto-engages the damper during perturbations, leading to a perturbation-trigger damping, improving robustness at a minimum energetic cost. With the results from the slack damper mechanism, we propose a new functional interpretation of animals' redundant muscle tendons as tunable dampers.
MeSH term(s)	Animals ; Locomotion/physiology ; Tendons ; Muscle, Skeletal/physiology
Language	English
Publishing date	2023-02-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-30318-3
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Article ; Online: Transduction of Ferret Surface and Basal Cells of Airways, Lung, Liver, and Pancreas via Intratracheal or Intravenous Delivery of Adeno-Associated Virus 1 or 6.

Yanda, Murali K / Zeidan, Adi / Ciobanu, Cristian / Izzi, Jessica / Guggino, William B / Cebotaru, Liudmila

Human gene therapy

2023 Volume 34, Issue 21-22, Page(s) 1135–1144

Abstract: Cystic fibrosis (CF) is potentially treatable by gene therapy. Since the identification of the CF gene, preclinical and clinical trials have concentrated on achieving effective gene therapy targeting the lung. However, the lung has proven to be a ... ...

Abstract	Cystic fibrosis (CF) is potentially treatable by gene therapy. Since the identification of the CF gene, preclinical and clinical trials have concentrated on achieving effective gene therapy targeting the lung. However, the lung has proven to be a formidable barrier to successful gene therapy especially for CF, and many clinical trials failed to achieve efficacy. Recent advances in vector design and adeno-associated virus (AAV) serotypes have increased the chances of success. Given that CF is a multi-organ disease, the goal of this study was to test whether a gene therapy approach involving AAV1 or AAV6 vector delivery via the systemic circulation would at the same time overcome the barrier of lung delivery and transduce organs commonly affected by CF. To accomplish this, we sprayed AAV1 containing green fluorescent protein (GFP) into the trachea or injected it intravenously (IV). We also tested AAV6 injected IV. No adverse events were noted. Ferrets were necropsied 30 days after vector delivery. AAV1 or AAV6 vector genomes, messenger RNA (mRNA) expression, and GFP were detected in all the tracheal and lung samples from the treated animals, whether AAV1 was sprayed into the trachea or injected IV or AAV6 was injected IV. Importantly, both surface epithelial and basal cells of the trachea and lung airways were successfully transduced, regardless of which route of delivery or vector serotype used for transduction. We detected also AAV1 and AAV6 vector genomes, mRNA expression, and GFP in the livers and pancreases, particularly in the acinar cells of the pancreatic duct. These data suggest that gene transfer is attainable in the airways, liver, and pancreas using either serotype, AAV1 or AAV6. Given that these same organs are affected in CF, systemic delivery of AAV may be the preferred route of delivery for a gene therapy for CF.
MeSH term(s)	Animals ; Ferrets/genetics ; Dependovirus/genetics ; Lung ; Liver ; Cystic Fibrosis ; Pancreas ; RNA, Messenger ; Genetic Vectors/genetics ; Transduction, Genetic
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2023-10-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	1028152-6
ISSN	1557-7422 ; 1043-0342
ISSN (online)	1557-7422
ISSN	1043-0342
DOI	10.1089/hum.2023.095
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Article: Muscle preflex response to perturbations in locomotion:

Araz, Matthew / Weidner, Sven / Izzi, Fabio / Badri-Spröwitz, Alexander / Siebert, Tobias / Haeufle, Daniel F B

Frontiers in bioengineering and biotechnology

2023 Volume 11, Page(s) 1150170

Abstract: Neuromuscular control loops feature substantial communication delays, but mammals run robustly even in the most adverse conditions. ...

Abstract	Neuromuscular control loops feature substantial communication delays, but mammals run robustly even in the most adverse conditions.
Language	English
Publishing date	2023-04-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2023.1150170
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Article ; Online: The feasibility of identifying health inequalities in social prescribing referrals and declines using primary care patient records.

Khan, Koser / Al-Izzi, Rachel / Montasem, Alexander / Gordon, Clare / Brown, Heather / Goldthorpe, Joanna

NIHR open research

2023 Volume 3, Page(s) 1

Abstract: Background: Social prescribing (SP) is part of universal personalised care and available to everyone in the UK National Health Service. However, emerging evidence suggests access disparities in social prescribing. This study aimed to investigate the ... ...

Abstract	Background: Social prescribing (SP) is part of universal personalised care and available to everyone in the UK National Health Service. However, emerging evidence suggests access disparities in social prescribing. This study aimed to investigate the feasibility of using primary care records to access and analyse data on social prescribing. Our secondary aim was to compare characteristics of patients who are offered referral, referred to or decline referral for social prescribing to explore possible inequalities in access to social prescribing. Methods: Patient records (n=3086) were extracted from 11 GP practices across Northwest England for accepted, offered and declined social prescribing referrals. Patient demographics collected included sex, age, ethnicity, mental and physical health diagnoses. Patient characteristics in social prescribing referrals were compared to the overall practice population (practice information from Public Health England). Referral and decline rates were compared by group (e.g. male/female decline rates). Results: GP referral data showed inconsistent recording of wider determinants of health. Patient age, sex and mental and physical health conditions were consistently recorded. Other variables (marital status, interpreter need, education, disability, sexual orientation, non-English language, nationality) were recorded only sporadically and could not be used for analysis. Practices varied in referral patterns. Our preliminary findings identified under-referring of younger age groups and Asians, and higher declined referrals among individuals with physical health diagnoses. Conclusions: Recording discrepancies meant that many patient factors could not be used to identify trends in social prescribing referrals and declines and assess equity. Primary care data recording must be consistent to understand SP referral trends and inequalities relating to the wider determinants of health. Preliminary results suggest some patient groups may be underrepresented in SP referrals, however this requires further investigation.
Language	English
Publishing date	2023-08-30
Publishing country	England
Document type	Journal Article
ISSN	2633-4402
ISSN (online)	2633-4402
DOI	10.3310/nihropenres.13325.2
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Article ; Online: Editorial - Sofosbuvir/Velpatasvir as a combination with strong potential activity against SARS-CoV2 (COVID-19) infection: how to use direct-acting antivirals as broad-spectrum antiviral agents.

Izzi, A / Messina, V / Rinaldi, L / Maggi, P

European review for medical and pharmacological sciences

2020 Volume 24, Issue 10, Page(s) 5193–5194

MeSH term(s)	Antiviral Agents/chemistry ; Antiviral Agents/metabolism ; Antiviral Agents/therapeutic use ; Betacoronavirus/isolation & purification ; COVID-19 ; Carbamates/therapeutic use ; Coronavirus Infections/drug therapy ; Coronavirus Infections/virology ; DNA-Directed DNA Polymerase/chemistry ; DNA-Directed DNA Polymerase/metabolism ; Drug Therapy, Combination ; Heterocyclic Compounds, 4 or More Rings/therapeutic use ; Humans ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/virology ; SARS-CoV-2 ; Sofosbuvir/chemistry ; Sofosbuvir/metabolism ; Sofosbuvir/therapeutic use ; Viral Proteins/chemistry ; Viral Proteins/metabolism
Chemical Substances	Antiviral Agents ; Carbamates ; Heterocyclic Compounds, 4 or More Rings ; Viral Proteins ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; velpatasvir (KCU0C7RS7Z) ; Sofosbuvir (WJ6CA3ZU8B)
Keywords	covid19
Language	English
Publishing date	2020-06-04
Publishing country	Italy
Document type	Editorial
ZDB-ID	605550-3
ISSN	2284-0729 ; 1128-3602 ; 0392-291X
ISSN (online)	2284-0729
ISSN	1128-3602 ; 0392-291X
DOI	10.26355/eurrev_202005_21297
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Article: Pan-Cancer Analysis of the Genomic Alterations and Mutations of the Matrisome.

Izzi, Valerio / Davis, Martin N / Naba, Alexandra

Cancers

2020 Volume 12, Issue 8

Abstract: The extracellular matrix (ECM) is a master regulator of all cellular functions and a major component of the tumor microenvironment. We previously defined the "matrisome" as the ensemble of genes encoding ECM proteins and proteins modulating ECM structure ...

Abstract	The extracellular matrix (ECM) is a master regulator of all cellular functions and a major component of the tumor microenvironment. We previously defined the "matrisome" as the ensemble of genes encoding ECM proteins and proteins modulating ECM structure or function. While compositional and biomechanical changes in the ECM regulate cancer progression, no study has investigated the genomic alterations of matrisome genes in cancers and their consequences. Here, mining The Cancer Genome Atlas (TCGA) data, we found that copy number alterations and mutations are frequent in matrisome genes, even more so than in the rest of the genome. We also found that these alterations are predicted to significantly impact gene expression and protein function. Moreover, we identified matrisome genes whose mutational burden is an independent predictor of survival. We propose that studying genomic alterations of matrisome genes will further our understanding of the roles of this compartment in cancer progression and will lead to the development of innovative therapeutic strategies targeting the ECM.
Language	English
Publishing date	2020-07-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12082046
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Article ; Online: Immunohistochemical Characterization of a Duodenal Adenocarcinoma with Pulmonary, Hepatic and Parapatellar Metastases in a Common Marmoset (Callithrixjacchus).

Peterson, Cornelia / Plunkard, Jessica / Johanson, Andrew / Izzi, Jessica / Gabrielson, Kathleen

Journal of comparative pathology

2021 Volume 189, Page(s) 1–7

Abstract: An 11-year-old male common marmoset (Callithrix jacchus) presented with chronic, progressive weight loss and diarrhoea. Response to treatment with nutritional supplementation, antibiotics and immunosuppressants was modest and transient, and the animal ... ...

Abstract	An 11-year-old male common marmoset (Callithrix jacchus) presented with chronic, progressive weight loss and diarrhoea. Response to treatment with nutritional supplementation, antibiotics and immunosuppressants was modest and transient, and the animal was humanely euthanized. At necropsy, the proximal 8 cm of small intestine was diffusely pale with transmural thickening. The lungs contained coalescing tan, firm nodules measuring up to 4 mm in diameter. Histological examination revealed infiltrative mucinous adenocarcinoma of the duodenum with extensive metastases to the lungs, liver and left parapatellar adipose tissue. The mucinous matrix secreted by the primary and metastatic lesions was strongly periodic acid-Schiff positive. Warthin Starry staining for spirochaetes was negative. Pancytokeratin expression was attenuated in the primary tumour as well as in the metastases, which correlated to a poorly differentiated phenotype. To the authors' knowledge, this is the first report of a proximal duodenal adenocarcinoma with extensive metastatic disease in a common marmoset.
MeSH term(s)	Adenocarcinoma/veterinary ; Animals ; Callithrix ; Duodenal Neoplasms/veterinary ; Liver ; Lung ; Male
Language	English
Publishing date	2021-10-19
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	390920-7
ISSN	1532-3129 ; 0021-9975
ISSN (online)	1532-3129
ISSN	0021-9975
DOI	10.1016/j.jcpa.2021.09.002
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