Distribution of the novel eNOS–interacting protein NOSIP in the liver, pancreas, and gastrointestinal tract of the rat

AbstractPII proteins constitute a widespread signal transduction superfamily in the prokaryotic world. The canonical PII signal proteins sense metabolic state of the cells by binding the metabolite molecules ATP, ADP and 2-oxoglutarate. Depending on bound effector molecule, PII proteins interact with and modulate the activity of multiple target proteins. To investigate the complexity of interactions of PII with target proteins, analytical methods that do not disrupt the native cellular context are required. To this purpose, split luciferase proteins have been used to develop a novel complementation reporter called NanoLuc Binary Technology (NanoBiT). The luciferase NanoLuc is divided in two subunits: a 18 kDa polypeptide termed “Large BiT” and a 1.3 kDa peptide termed “Small BiT”, which only weakly associate. When fused to proteins of interest, they reconstitute an active luciferase when the proteins of interest interact. Therefore, we set out to develop a new NanoBiT sensor based on the interaction of PII protein from Synechocystis sp. PCC6803 with PII-interacting protein X (PipX) and N-acetyl-L-glutamate kinase (NAGK). The novel NanoBiT sensor showed unprecedented sensitivity, which made it possible to detect even weak and transient interactions between PII variants and their interacting partners, thereby shedding new light in PII signalling processes.

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COVID-19 Vaccination: From Interesting Agent to the Patient

Vaccines ◽

10.3390/vaccines9020120 ◽

2021 ◽

Vol 9 (2) ◽

pp. 120

Author(s):

Anis Daou

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Gastrointestinal Tract ◽

Circulatory System ◽

The Novel ◽

Lead Compound ◽

Fda Approval ◽

The World ◽

The Central Nervous System ◽

Novel Coronavirus

The vaccination for the novel Coronavirus (COVID-19) is undergoing its final stages of analysis and testing. It is an impressive feat under the circumstances that we are on the verge of a potential breakthrough vaccination. This will help reduce the stress for millions of people around the globe, helping to restore worldwide normalcy. In this review, the analysis looks into how the new branch of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) came into the forefront of the world like a pandemic. This review will break down the details of what COVID-19 is, the viral family it belongs to and its background of how this family of viruses alters bodily functions by attacking vital human respiratory organs, the circulatory system, the central nervous system and the gastrointestinal tract. This review also looks at the process a new drug analogue undergoes, from (i) being a promising lead compound to (ii) being released into the market, from the drug development and discovery stage right through to FDA approval and aftermarket research. This review also addresses viable reasoning as to why the SARS-CoV-2 vaccine may have taken much less time than normal in order for it to be released for use.

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Phosphorylation of KLC1 modifies interaction with JIP1 and abolishes the enhanced fast velocity of APP transport by kinesin-1

Molecular Biology of the Cell ◽

10.1091/mbc.e17-05-0303 ◽

2017 ◽

Vol 28 (26) ◽

pp. 3857-3869 ◽

Cited By ~ 4

Author(s):

Kyoko Chiba ◽

Ko-yi Chien ◽

Yuriko Sobu ◽

Saori Hata ◽

Shun Kato ◽

...

Keyword(s):

Coiled Coil ◽

Amyloid Β ◽

Tetratricopeptide Repeat ◽

Amyloid Β Protein ◽

The Novel ◽

Anterograde Transport ◽

Interacting Protein ◽

Protein Precursor ◽

Kinesin Light Chain ◽

Β Protein

In neurons, amyloid β-protein precursor (APP) is transported by binding to kinesin-1, mediated by JNK-interacting protein 1b (JIP1b), which generates the enhanced fast velocity (EFV) and efficient high frequency (EHF) of APP anterograde transport. Previously, we showed that EFV requires conventional interaction between the JIP1b C-terminal region and the kinesin light chain 1 (KLC1) tetratricopeptide repeat, whereas EHF requires a novel interaction between the central region of JIP1b and the coiled-coil domain of KLC1. We found that phosphorylatable Thr466 of KLC1 regulates the conventional interaction with JIP1b. Substitution of Glu for Thr466 abolished this interaction and EFV, but did not impair the novel interaction responsible for EHF. Phosphorylation of KLC1 at Thr466 increased in aged brains, and JIP1 binding to kinesin-1 decreased, suggesting that APP transport is impaired by aging. We conclude that phosphorylation of KLC1 at Thr466 regulates the velocity of transport of APP by kinesin-1 by modulating its interaction with JIP1b.

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WZsGreen/+: a new green fluorescent protein knock-in mouse model for the study of KIT-expressing cells in gut and cerebellum

Physiological Genomics ◽

10.1152/physiolgenomics.00105.2005 ◽

2005 ◽

Vol 22 (3) ◽

pp. 412-421 ◽

Cited By ~ 19

Author(s):

Mira Wouters ◽

Karine Smans ◽

Jean-Marie Vanderwinden

Keyword(s):

Small Intestine ◽

Green Fluorescent Protein ◽

Gastrointestinal Tract ◽

Molecular Mechanisms ◽

Fluorescent Protein ◽

Molecular Layer ◽

Transgenic Animals ◽

The Novel ◽

Suitable Alternative ◽

Green Fluorescent

In the small intestine, interstitial cells of Cajal (ICC) surrounding the myenteric plexus generate the pacemaking slow waves that are essential for an efficient intestinal transit. The underlying molecular mechanisms of the slow wave are poorly known. KIT is currently the sole practical marker for ICC. Attempts to purify living ICC have so far largely failed, due to the loss of the KIT epitope during enzymatic dissociation. Aiming to identify and isolate living ICC, we designed a knock-in strategy to express a fluorescent tag in KIT-expressing cells by inserting the sequence of the novel green fluorescent protein ZsGreen into the first exon of the c-Kit gene, creating a null allele called WZsGreen. In the gastrointestinal tract of heterozygous WZsGreen/+ mice, tiny ZsGreen fluorescent dots were observed in all KIT-expressing ICC populations, with exception of ICC at the deep muscular plexus in small intestine. During development of the gastrointestinal tract, ZsGreen expression followed KIT expression in a spatiotemporal way. Stellate and basket KIT-expressing cells in the molecular layer of the cerebellum also exhibited ZsGreen dots, whereas no ZsGreen was detected in skin, testis, and bone marrow. ZsGreen dot-containing intestinal cells could be isolated from jejunum and maintained alive in culture for at least 3 days. ZsGreen is a suitable alternative to EGFP in transgenic animals. The novel WZsGreen/+ model reported here appears to be a promising tool for live studies of KIT-expressing cells in the gastrointestinal tract and cerebellum and for the further analysis of pacemaker mechanisms.

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Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport

Molecular Biology of the Cell ◽

10.1091/mbc.e14-06-1111 ◽

2014 ◽

Vol 25 (22) ◽

pp. 3569-3580 ◽

Cited By ~ 35

Author(s):

Kyoko Chiba ◽

Masahiko Araseki ◽

Keisuke Nozawa ◽

Keiko Furukori ◽

Yoichi Araki ◽

...

Keyword(s):

Quantitative Analysis ◽

Axonal Transport ◽

High Frequency ◽

Coiled Coil ◽

Tetratricopeptide Repeat ◽

The Novel ◽

Anterograde Transport ◽

Interacting Protein ◽

A Site

Alzheimer's β-amyloid precursor protein (APP) associates with kinesin-1 via JNK-interacting protein 1 (JIP1); however, the role of JIP1 in APP transport by kinesin-1 in neurons remains unclear. We performed a quantitative analysis to understand the role of JIP1 in APP axonal transport. In JIP1-deficient neurons, we find that both the fast velocity (∼2.7 μm/s) and high frequency (66%) of anterograde transport of APP cargo are impaired to a reduced velocity (∼1.83 μm/s) and a lower frequency (45%). We identified two novel elements linked to JIP1 function, located in the central region of JIP1b, that interact with the coiled-coil domain of kinesin light chain 1 (KLC1), in addition to the conventional interaction of the JIP1b 11–amino acid C-terminal (C11) region with the tetratricopeptide repeat of KLC1. High frequency of APP anterograde transport is dependent on one of the novel elements in JIP1b. Fast velocity of APP cargo transport requires the C11 domain, which is regulated by the second novel region of JIP1b. Furthermore, efficient APP axonal transport is not influenced by phosphorylation of APP at Thr-668, a site known to be phosphorylated by JNK. Our quantitative analysis indicates that enhanced fast-velocity and efficient high-frequency APP anterograde transport observed in neurons are mediated by novel roles of JIP1b.

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Mo1798 Sampling of the Mucosal Microbiota in the Upper Gastrointestinal Tract: A Comparison of the Novel Brisbane Aseptic Mucosal Sampling Device Versus Standard Biopsy

Gastroenterology ◽

10.1016/s0016-5085(15)32428-8 ◽

2015 ◽

Vol 148 (4) ◽

pp. S-714

Author(s):

Erin Shanahan ◽

Mark Morrison ◽

Nicholas J. Talley ◽

Natasha A. Koloski ◽

Marjorie M. Walker ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Upper Gastrointestinal Tract ◽

The Novel ◽

Sampling Device ◽

Upper Gastrointestinal

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First clinical experiences with a novel endoscopic over-the-scope clip system

Endoscopy International Open ◽

10.1055/s-0043-101692 ◽

2017 ◽

Vol 05 (03) ◽

pp. E151-E156 ◽

Cited By ~ 17

Author(s):

Marco Dinelli ◽

Barbara Omazzi ◽

Paolo Andreozzi ◽

Nicola Zucchini ◽

Alessandro Redaelli ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Clinical Success ◽

Endocrine Tumor ◽

Intestinal Wall ◽

R0 Resection ◽

The Novel ◽

Clinical Experiences ◽

Endoscopic Full Thickness Resection ◽

Over The Scope Clip ◽

Otsc System

AbstractWe describe our experience with a new over-the-scope clip (OTSC) system (Padlock Clip™) in the treatment of 14 patients. Eight of the 14 patients were treated for closure of gastrointestinal fistulas (n = 4), iatrogenic gastrointestinal perforations (n = 2), or hemostasis of post-polypectomy bleeding (n = 2). The site of clipping was the lower gastrointestinal tract in five patients and the upper gastrointestinal tract in three patients. The clip was successfully delivered in seven out of the eight patients and clinical success was achieved in all patients. Endoscopic full thickness resection (EFTR) was performed to treat six patients: four with recurrent adenoma (n = 4), one with ulcerated nodules at ileorectal anastomosis, and one with a neuro-endocrine tumor of the rectum. A complete intestinal wall resection was achieved in three of the six patients (50 %) and an R0 resection in five of the six patients (83.3 %). No complications related to the procedure and no recurrence at endoscopic follow-up were observed in any patient. The novel Padlock Clip seems to be an effective and safe tool to treat gastrointestinal fistulas, perforations or post-polypectomy bleeding, and to perform EFTR.

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Pathogenetic approach to the treatment of functional disorders of the gastrointestinal tract and their intersection: Results of the Russian Observation Retrospective Program COMFORT

10.21203/rs.2.13285/v1 ◽

2019 ◽

Author(s):

Vladimir Ivashkin ◽

Elena Poluektova ◽

Alexey Glazunov ◽

Mikhail A Putilovskiy ◽

Oleg I Epstein

Keyword(s):

Gastrointestinal Tract ◽

Active Form ◽

The Novel ◽

Functional Disorders ◽

Efficacy Analysis ◽

Combination Methods ◽

S 100 ◽

Effect Of Treatment ◽

Irritable Bowel ◽

Factor Α

Abstract Background The aim of this study was to investigate the efficacy and safety of the novel complex drug, consisting of released-active form of antibodies to S-100 protein, tumor necrosis factor-α and histamine, (Kolofort) under outpatient conditions in patients with functional dyspepsia (FD), irritable bowel syndrome (IBS), and their combination. Methods The subject of the observational noninterventional retrospective program was the data of 14,362 outpatient records of patients with diagnosed FD, IBS, and/or their combination who received the drug Kolofort in monotherapy for 12 weeks, 2 tablets twice a day. To assess the presence and severity of symptoms of functional disorders of the gastrointestinal tract (FD GIT), a questionnaire “7*7” developed by a working group from the Russian Gastroenterological Association was used. The evaluated parameters included the proportion of patients: who had a reduction in the number of points by 50% or more; who have decreased the severity category of the condition; who have switched to the “healthy” and “borderline ill” severity categories;and the change in the number of points in domains 1–7. Results The final efficacy analysis included data from 9,254 patients. A decrease in the number of points by 50% or more was observed in 80.45% of patients with FD, 79.02% of patients with IBS, and in 83% of patients with both IBS and FD. A decrease in the severity category of the condition at the end of therapy was noted in 93.35% of patients with FD, in 93.80% of cases in patients with IBS, and in 96.17% of cases in patients with a combination of IBS and FD.A total of 94 adverse events (AEs) were reported in 80 patients (0.65%). Conclusion The COMFORT program has demonstrated the positive effect of treatment in the majority of patients with IBS and FD and their combination in real clinical practice.

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