scholarly journals C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage in ER-to-Golgi trafficking

2011 ◽  
Vol 22 (12) ◽  
pp. 2083-2093 ◽  
Author(s):  
P. James Scrivens ◽  
Baraa Noueihed ◽  
Nassim Shahrzad ◽  
Sokunthear Hul ◽  
Stephanie Brunet ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Multidisciplinary Approach ◽  
Early Stage ◽  
Binary Interaction ◽  
The Novel ◽  
Novel Proteins ◽  
Bona Fide ◽  
Interaction Map ◽  
Equivalent Complex

TRAPP is a multisubunit tethering complex implicated in multiple vesicle trafficking steps in Saccharomyces cerevisiae and conserved throughout eukarya, including humans. Here we confirm the role of TRAPPC2L as a stable component of mammalian TRAPP and report the identification of four novel components of the complex: C4orf41, TTC-15, KIAA1012, and Bet3L. Two of the components, KIAA1012 and Bet3L, are mammalian homologues of Trs85p and Bet3p, respectively. The remaining two novel TRAPP components, C4orf41 and TTC-15, have no homologues in S. cerevisiae. With this work, human homologues of all the S. cerevisiae TRAPP proteins, with the exception of the Saccharomycotina-specific subunit Trs65p, have now been reported. Through a multidisciplinary approach, we demonstrate that the novel proteins are bona fide components of human TRAPP and implicate C4orf41 and TTC-15 (which we call TRAPPC11 and TRAPPC12, respectively) in ER-to-Golgi trafficking at a very early stage. We further present a binary interaction map for all known mammalian TRAPP components and evidence that TRAPP oligomerizes. Our data are consistent with the absence of a TRAPP I–equivalent complex in mammalian cells, suggesting that the fundamental unit of mammalian TRAPP is distinct from that characterized in S. cerevisiae.

scholarly journals Gallbladder cancer revisited: the evolving role of a radiologist

2021 ◽  
Vol 94 (1117) ◽  
pp. 20200726
Author(s):  
Anupama Ramachandran ◽  
Deep Narayan Srivastava ◽  
Kumble Seetharama Madhusudhan
Keyword(s):  
Gallbladder Cancer ◽  
Surgical Resection ◽  
Median Survival ◽  
Multidisciplinary Approach ◽  
Early Stage ◽  
Survival Duration ◽  
Advanced Stage ◽  
Complete Surgical Resection ◽  
Common Malignancy

Gallbladder cancer is the most common malignancy of the biliary tract. It is also the most aggressive biliary tumor with the shortest median survival duration. Complete surgical resection, the only potentially curative treatment, can be accomplished only in those patients who are diagnosed at an early stage of the disease. Majority (90%) of the patients present at an advanced stage and the management involves a multidisciplinary approach. The role of imaging in gallbladder cancer cannot be overemphasized. Imaging is crucial not only in detecting, staging, and planning management but also in guiding radiological interventions. This article discusses the role of a radiologist in the diagnosis and management of gallbladder cancer.

scholarly journals Laccase-Catalyzed 1,4-Dioxane-Mediated Synthesis of Belladine N-Oxides with Anti-Influenza A Virus Activity

2021 ◽  
Vol 22 (3) ◽  
pp. 1337
Author(s):  
Claudio Zippilli ◽  
Lorenzo Botta ◽  
Bruno Mattia Bizzarri ◽  
Lucia Nencioni ◽  
Marta De Angelis ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Functional Group ◽  
Early Stage ◽  
Side Chain ◽  
The Novel ◽  
Paramagnetic Resonance ◽  
Electron Paramagnetic ◽  
Mediated Oxidation

Belladine N-oxides active against influenza A virus have been synthetized by a novel laccase-catalyzed 1,4-dioxane-mediated oxidation of aromatic and side-chain modified belladine derivatives. Electron paramagnetic resonance (EPR) analysis confirmed the role of 1,4-dioxane as a co-oxidant. The reaction was chemo-selective, showing a high functional-group compatibility. The novel belladine N-oxides were active against influenza A virus, involving the early stage of the virus replication life cycle.

scholarly journals Hydrogen Sulfide Biochemistry and Interplay with Other Gaseous Mediators in Mammalian Physiology

2018 ◽  
Vol 2018 ◽  
pp. 1-31 ◽  
Author(s):  
Alessandro Giuffrè ◽  
João B. Vicente
Keyword(s):  
Hydrogen Sulfide ◽  
Mammalian Cells ◽  
Protein Targets ◽  
Metal Centers ◽  
Cellular Processes ◽  
Signaling Function ◽  
Enzymatic Systems ◽  
Bona Fide ◽  
Different Levels

Hydrogen sulfide (H2S) has emerged as a relevant signaling molecule in physiology, taking its seat as a bona fide gasotransmitter akin to nitric oxide (NO) and carbon monoxide (CO). After being merely regarded as a toxic poisonous molecule, it is now recognized that mammalian cells are equipped with sophisticated enzymatic systems for H2S production and breakdown. The signaling role of H2S is mainly related to its ability to modify different protein targets, particularly by promoting persulfidation of protein cysteine residues and by interacting with metal centers, mostly hemes. H2S has been shown to regulate a myriad of cellular processes with multiple physiological consequences. As such, dysfunctional H2S metabolism is increasingly implicated in different pathologies, from cardiovascular and neurodegenerative diseases to cancer. As a highly diffusible reactive species, the intra- and extracellular levels of H2S have to be kept under tight control and, accordingly, regulation of H2S metabolism occurs at different levels. Interestingly, even though H2S, NO, and CO have similar modes of action and parallel regulatory targets or precisely because of that, there is increasing evidence of a crosstalk between the three gasotransmitters. Herein are reviewed the biochemistry, metabolism, and signaling function of hydrogen sulfide, as well as its interplay with the other gasotransmitters, NO and CO.

Regulatory considerations, challenges and risk-based approach in nanomedicine development

2021 ◽  
Vol 28 ◽  
Author(s):  
Ildikó Csóka ◽  
Ruba Ismail ◽  
Orsolya Jójárt-Laczkovich ◽  
Edina Pallagi
Keyword(s):  
Safety Assessment ◽  
Multidisciplinary Approach ◽  
Early Stage ◽  
Scale Up ◽  
Physicochemical Characteristics ◽  
The Novel ◽  
Safety And Efficacy ◽  
The Status ◽  
Regulatory Bodies

: The translation of nanomedicines from the lab level into marketed product face several challenges including characterization of physicochemical properties, pharmacodynamics, pharmacokinetics, process control, biocompatibility and nanotoxicity, scale-up as well as reproducibility. The challenges of nanomedicine development are in connection with the different requirements from the patient (clinical and therapeutic use), industry (production) and regulatory bodies (authorization process). This paper aims at reviewing the status and regulatory aspects of nano-based drug delivery systems with a focus on the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) regulations. In addition to discussing the risks accompanied by the development of nanomedicine, the potential of following a risk-based methodology from the early stage of the R&D phase is emphasized here to ensure safety and efficacy when developing novel nano-based dosage forms. Nanomedicines R&D is a complex and multidisciplinary approach and there are still many challenges in their regulation and legislation. In general, the most critical considerations for nanomedicines are the product quality assessment (physicochemical characteristics, quality control, manufacturing process) and product safety assessment (pharmacokinetics, biodegradation, accumulation and nanotoxicity). The paper presents a promising paradigm in the development and marketing authorization of nanomedicines, namely the Quality by Design (QbD) approach. Sufficient knowledge on the quality, safety, and efficacy of nanomedicines is necessary to obtain with a significant focus on establishing robust, standardized methods to evaluate the critical quality attributes of nanomedicines. The QbD-based submission is highly recommended and required by the regulatory authorities and will enable a smooth clinical translation of the novel nanomedicines.

scholarly journals Clinical Application of the Novel Cell-Based Biosensor for the Ultra-Rapid Detection of the SARS-CoV-2 S1 Spike Protein Antigen: A Practical Approach

Biosensors ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 224
Author(s):  
Sophie Mavrikou ◽  
Vasileios Tsekouras ◽  
Kyriaki Hatziagapiou ◽  
Foteini Paradeisi ◽  
Petros Bakakos ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Early Stage ◽  
False Negative ◽  
Sample Pretreatment ◽  
High Sensitivity ◽  
Spike Protein ◽  
The Novel ◽  
Major Step ◽  
Negative Results ◽  
Potential Applicability

The availability of antigen tests for SARS-CoV-2 represents a major step for the mass surveillance of the incidence of infection, especially regarding COVID-19 asymptomatic and/or early-stage patients. Recently, we reported the development of a Bioelectric Recognition Assay-based biosensor able to detect the SARS-CoV-2 S1 spike protein expressed on the surface of the virus in just three minutes, with high sensitivity and selectivity. The working principle was established by measuring the change of the electric potential of membrane-engineered mammalian cells bearing the human chimeric spike S1 antibody after attachment of the respective viral protein. In the present study, we applied the novel biosensor to patient-derived nasopharyngeal samples in a clinical set-up, with absolutely no sample pretreatment. More importantly, membrane-engineered cells were pre-immobilized in a proprietary biomatrix, thus enabling their long-term preservation prior to use as well as significantly increasing their ease-of-handle as test consumables. The plug-and-apply novel biosensor was able to detect the virus in positive samples with a 92.8% success rate compared to RT-PCR. No false negative results were recorded. These findings demonstrate the potential applicability of the biosensor for the early, routine mass screening of SARS-CoV-2 on a scale not yet realized.

Contrasting role of Autophagy in Different types of Cancer: A review towards biomarkers & therapeutic improvement

2020 ◽  
Author(s):  
Pallab Chakraborty
Keyword(s):  
Mammalian Cells ◽  
Energy Homeostasis ◽  
Building Blocks ◽  
Tumor Promoter ◽  
The Novel ◽  
Research Papers ◽  
Different Types ◽  
Cellular Control ◽  
Near Future

Autophagy, the major cellular pathway known for not only the degradation and recycling in mammalian cells but also it maintain the cellular energy homeostasis and produced the building blocks. Unfortunately, if the process starts to degrade the essential ones and ignored the bad proteins, and then the normal cellular control will be lost, that we see in case of cancer. It has been reported by several research papers that the novel pathway has paradoxical role in cancer, as it acts as both tumor promoter and suppressors. Therefore, autophagy could provide new resources for the improvement of antitumor drugs in near future. Here in this review we will know about the autophagy process, its contrasting role in different types of cancer, its significance as prognostic markers and its therapeutic implication for better cancer treatment in the near future.

scholarly journals Lamp1 mediates lipid transport, but is dispensable for autophagy in Drosophila

2021 ◽  
Author(s):  
Norin Chaudhry ◽  
Margaux Sica ◽  
Satya Surabhi ◽  
David Sanchez Hernandez ◽  
Ana Mesquita ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Double Mutant ◽  
Energy State ◽  
Lipid Transport ◽  
Cholesterol Trafficking ◽  
Ideal Model ◽  
Lipid Species ◽  
Bona Fide ◽  
Acidic Compartment

AbstractThe endolysosomal system not only is an integral part of the cellular catabolic machinery that processes and recycles nutrients for synthesis of biomaterials, but also acts as signaling hub to sense and coordinate the energy state of cells with growth and differentiation. Lysosomal dysfunction adversely influences vesicular transport-dependent macromolecular degradation and thus causes serious problems for human health. In mammalian cells, loss of the lysosome associated membrane proteins LAMP1/2 strongly impacts autophagy and cholesterol trafficking. Here we show that the previously uncharacterized Drosophila Lamp1 is a bona fide homolog of vertebrate LAMP1/2. Surprisingly and in contrast to Lamp1/2 double mutant mice, Drosophila Lamp1 is not required for viability or autophagy, suggesting that autophagy defects in Lamp1/2 mutants may have indirect causes. However, Lamp1 deficiency results in an expansion of the acidic compartment in flies. Furthermore, we find that Lamp1 mutant larvae have defects in lipid metabolism as they show elevated levels of sterols and diacylglycerols (DAGs). Since DAGs are the main lipid species used for transport though the hemolymph (blood) in insects, our results indicate broader functions of Lamp1 in lipid transport. Our findings make Drosophila an ideal model to study the role of LAMP proteins in lipid assimilation without the confounding effects of their storage and without interfering with autophagic processes.

scholarly journals Development of a Portable, Ultra-Rapid and Ultra-Sensitive Cell-Based Biosensor for the Direct Detection of the SARS-CoV-2 S1 Spike Protein Antigen

Sensors ◽  
2020 ◽  
Vol 20 (11) ◽  
pp. 3121 ◽  
Author(s):  
Sophie Mavrikou ◽  
Georgia Moschopoulou ◽  
Vasileios Tsekouras ◽  
Spyridon Kintzios
Keyword(s):  
Mammalian Cells ◽  
Direct Detection ◽  
Early Stage ◽  
Cross Reactivity ◽  
Considerable Change ◽  
Concept Development ◽  
Spike Protein ◽  
The Novel ◽  
Membrane Bound ◽  
Eventual Control

One of the key challenges of the recent COVID-19 pandemic is the ability to accurately estimate the number of infected individuals, particularly asymptomatic and/or early-stage patients. We herewith report the proof-of-concept development of a biosensor able to detect the SARS-CoV-2 S1 spike protein expressed on the surface of the virus. The biosensor is based on membrane-engineered mammalian cells bearing the human chimeric spike S1 antibody. We demonstrate that the attachment of the protein to the membrane-bound antibodies resulted in a selective and considerable change in the cellular bioelectric properties measured by means of a Bioelectric Recognition Assay. The novel biosensor provided results in an ultra-rapid manner (3 min), with a detection limit of 1 fg/mL and a semi-linear range of response between 10 fg and 1 μg/mL. In addition, no cross-reactivity was observed against the SARS-CoV-2 nucleocapsid protein. Furthermore, the biosensor was configured as a ready-to-use platform, including a portable read-out device operated via smartphone/tablet. In this way, we demonstrate that the novel biosensor can be potentially applied for the mass screening of SARS-CoV-2 surface antigens without prior sample processing, therefore offering a possible solution for the timely monitoring and eventual control of the global coronavirus pandemic.

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