Cellular Signaling Crosstalk Between Multiple Receptors for Investigation of Pathophysiology in Multifactorial Diseases - What is Clinically-Relevant Crosstalk?

Abstract MicroRNAs (miRNAs) are a set of short non-coding RNAs that play significant regulatory roles in cells. The study of miRNA data produced by Next-Generation Sequencing techniques can be of valid help for the analysis of multifactorial diseases, such as Multiple Sclerosis (MS). Although extensive studies have been conducted on young adults affected by MS, very little work has been done to investigate the pathogenic mechanisms in pediatric patients, and none from a machine learning perspective. In this work, we report the experimental results of a classification study aimed at evaluating the effectiveness of machine learning methods in automatically distinguishing pediatric MS from healthy children, based on their miRNA expression profiles. Additionally, since Attention Deficit Hyperactivity Disorder (ADHD) shares some cognitive impairments with pediatric MS, we also included patients affected by ADHD in our study. Encouraging results were obtained with an artificial neural network model based on a set of features automatically selected by feature selection algorithms. The results obtained show that models developed on automatically selected features overcome models based on a set of features selected by human experts. Developing an automatic predictive model can support clinicians in early MS diagnosis and provide new insights that can help find novel molecular pathways involved in MS disease.

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Effect of Probiotics and Prebiotics on Oral Health

Dental Journal of Advance Studies ◽

10.1055/s-0040-1722523 ◽

2021 ◽

Author(s):

Goutam Nanavati ◽

T. Prasanth ◽

Manab Kosala ◽

Sujit K. Bhandari ◽

Pamil Banotra

Keyword(s):

Oral Health ◽

Oral Cavity ◽

Periodontal Diseases ◽

Microbial Flora ◽

Gastrointestinal Disorders ◽

Food Ingredients ◽

Multifactorial Diseases ◽

Probiotic Strains ◽

Reducing Bacteria ◽

Nitrate Reducing Bacteria

AbstractProbiotics are the living microorganisms that have been commonly used in the prevention of gastrointestinal disorders. In recent times, probiotic and prebiotics have been used to assess and develop a natural balance of the microbial flora in the respiratory tract and the oral cavity as an adjunct therapy. They are known to augment the existing microbial flora that is beneficial to the host. Prebiotics are nondigestible food ingredients that help in increasing populations of probiotic bacteria. Recent studies have shown that probiotics help in active reduction in gingivitis, dental caries, periodontitis, and halitosis by replacing the harmful oral species, by means of utilizing abundant health-associated oral microbial species. Additionally, the nitrate-reducing bacteria have shown promising effect in improving efficiency of probiotic strains to accentuate oral health benefits. Probiotics along with prebiotics effectively alter the host–microbial interface by achieving homeostasis in multifactorial diseases such as periodontal diseases and oral malodor. The aim of the review is to collate the existing information available on use of probiotics and prebiotics in oral cavity.

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Multiple receptors linked to inhibition of adenylate cyclase accelerate Na+/H+ exchange in neuroblastoma x glioma cells via a mechanism other than decreased cAMP accumulation.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)45409-9 ◽

1987 ◽

Vol 262 (36) ◽

pp. 17504-17509 ◽

Cited By ~ 5

Author(s):

L L Isom ◽

E J Cragoe ◽

L E Limbird

Keyword(s):

Adenylate Cyclase ◽

Glioma Cells ◽

Camp Accumulation ◽

Multiple Receptors

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Intracellular Ionic Strength Sensing Using NanoLuc

International Journal of Molecular Sciences ◽

10.3390/ijms22020677 ◽

2021 ◽

Vol 22 (2) ◽

pp. 677

Author(s):

Tausif Altamash ◽

Wesam Ahmed ◽

Saad Rasool ◽

Kabir H. Biswas

Keyword(s):

Thermal Stability ◽

Phase Separation ◽

Drug Discovery ◽

Ionic Strength ◽

Cellular Signaling ◽

Live Cells ◽

Protein Activity ◽

Cellular Survival ◽

Cellular Processes ◽

Wide Range

Intracellular ionic strength regulates myriad cellular processes that are fundamental to cellular survival and proliferation, including protein activity, aggregation, phase separation, and cell volume. It could be altered by changes in the activity of cellular signaling pathways, such as those that impact the activity of membrane-localized ion channels or by alterations in the microenvironmental osmolarity. Therefore, there is a demand for the development of sensitive tools for real-time monitoring of intracellular ionic strength. Here, we developed a bioluminescence-based intracellular ionic strength sensing strategy using the Nano Luciferase (NanoLuc) protein that has gained tremendous utility due to its high, long-lived bioluminescence output and thermal stability. Biochemical experiments using a recombinantly purified protein showed that NanoLuc bioluminescence is dependent on the ionic strength of the reaction buffer for a wide range of ionic strength conditions. Importantly, the decrease in the NanoLuc activity observed at higher ionic strengths could be reversed by decreasing the ionic strength of the reaction, thus making it suitable for sensing intracellular ionic strength alterations. Finally, we used an mNeonGreen–NanoLuc fusion protein to successfully monitor ionic strength alterations in a ratiometric manner through independent fluorescence and bioluminescence measurements in cell lysates and live cells. We envisage that the biosensing strategy developed here for detecting alterations in intracellular ionic strength will be applicable in a wide range of experiments, including high throughput cellular signaling, ion channel functional genomics, and drug discovery.

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Business intelligence tools to optimize the appropriateness of the diagnostic process for clinical and epidemiologic purposes in a multicenter veterinary pathology service

Journal of Veterinary Diagnostic Investigation ◽

10.1177/10406387211003163 ◽

2021 ◽

pp. 104063872110031

Author(s):

Nicola Pozzato ◽

Laura D’Este ◽

Laura Gagliazzo ◽

Marta Vascellari ◽

Monia Cocchi ◽

...

Keyword(s):

Business Intelligence ◽

Reporting System ◽

Animal Health ◽

Final Diagnosis ◽

Information Management System ◽

Daily Basis ◽

Diagnostic Process ◽

Multifactorial Diseases ◽

Specific Syndrome ◽

Veterinary Pathology

Laboratory tests provide essential support to the veterinary practitioner, and their use has grown exponentially. This growth is the result of several factors, such as the eradication of historical diseases, the occurrence of multifactorial diseases, and the obligation to control endemic and epidemic diseases. However, the introduction of novel techniques is counterbalanced by economic constraints, and the establishment of evidence- and consensus-based guidelines is essential to support the pathologist. Therefore, we developed standardized protocols, categorized by species, type of production, age, and syndrome at the Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), a multicenter institution for animal health and food safety. We have 72 protocols in use for livestock, poultry, and pets, categorized as, for example, “bovine enteric calf”, “rabbit respiratory”, “broiler articular”. Each protocol consists of a panel of tests, divided into ‘mandatory’ and ‘ancillary’, to be selected by the pathologist in order to reach the final diagnosis. After autopsy, the case is categorized into a specific syndrome, subsequently referred to as a syndrome-specific panel of analyses. The activity of the laboratories is monitored through a web-based dynamic reporting system developed using a business intelligence product (QlikView) connected to the laboratory information management system (IZILAB). On a daily basis, reports become available at general, laboratory, and case levels, and are updated as needed. The reporting system highlights epidemiologic variations in the field and allows verification of compliance with the protocols within the organization. The diagnostic protocols are revised annually to increase system efficiency and to address stakeholder requests.

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Pseudomonas aeruginosa uses multiple receptors for adherence to laminin during infection of the respiratory tract and skin wounds

Scientific Reports ◽

10.1038/s41598-019-54622-z ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Magnus Paulsson ◽

Yu-Ching Su ◽

Tamara Ringwood ◽

Fabian Uddén ◽

Kristian Riesbeck

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Outer Membrane ◽

Heparin Binding ◽

Surface Receptors ◽

Binding Domains ◽

Laminin Receptors ◽

Multiple Receptors ◽

Main Component ◽

Tract Infections

AbstractPseudomonas aeruginosa efficiently adheres to human tissues, including the lungs and skin, causing infections that are difficult to treat. Laminin is a main component of the extracellular matrix, and in this study we defined bacterial laminin receptors on P. aeruginosa. Persistent clinical P. aeruginosa isolates from patients with cystic fibrosis, wounds or catheter-related urinary tract infections bound more laminin compared to blood isolates. Laminin receptors in the outer membrane were revealed by 2D-immunblotting, and the specificities of interactions were confirmed with ELISA and biolayer interferometry. Four new high-affinity laminin receptors were identified in the outer membrane; EstA, OprD, OprG and PA3923. Mutated bacteria devoid of these receptors adhered poorly to immobilized laminin. All bacterial receptors bound to the heparin-binding domains on LG4 and LG5 of the laminin alpha chain as assessed with truncated laminin fragments, transmission electron microscopy and inhibition by heparin. In conclusion, P. aeruginosa binds laminin via multiple surface receptors, and isolates from lungs of cystic fibrosis patients bound significantly more laminin compared to bacteria isolated from the skin and urine. Since laminin is abundant in both the lungs and skin, we suggest that laminin binding is an important mechanism in P. aeruginosa pathogenesis.

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Reference values of plasma homocysteine in Cuban children and adults

LaboratoriumsMedizin ◽

10.1515/labmed-2019-0195 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Alina Concepción Alvarez ◽

Ivette Camayd Viera ◽

Lisy Vento Buigues ◽

Yanet Fernández Martínez ◽

Eraida Hernández ◽

...

Keyword(s):

Reference Values ◽

High Performance ◽

Age Groups ◽

Coffee Consumption ◽

Reference Interval ◽

Reference Intervals ◽

Multifactorial Diseases ◽

Weak Association ◽

Different Populations ◽

Cuban Population

AbstractObjectivesHomocysteine (Hcy) is a nonessential amino acid, produced by the demethylation of methionine. High Hcy levels, or hyperhomocysteinemia, have been associated with genetic and multifactorial diseases. Hcy reference values may vary between different populations, as Hcy levels are affected by factors such as sex, age, diet, smoking, and coffee consumption. The estimation reference interval (RI) allows to establish the normal values of this marker in population. At present, these levels are unknown in Cuba. The aim of this work is to estimate the Hcy reference intervals in Cuban children and adults.MethodsTotal Hcy concentration was quantified by high performance liquid chromatography (HPLC) in plasma. Hcy levels were evaluated in samples from 507 healthy individuals (260 children, 247 adults).ResultsRIs were estimated by nonparametric methods. We found significant differences between both age groups, but we did not find significant differences between sexes, within these groups. The established ranges were 2.56–14.55 µM and 3.63–17.19 µM for children and adults, respectively. Also, we observed a weak association between Hcy levels and age in both sex groups.ConclusionsThis is the first study that assesses Hcy reference values in Cuban population. Our results will allow the introduction of Hcy as a biochemical marker in laboratory testing.

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