scholarly journals Characterization of Strip1 Expression in Mouse Cochlear Hair Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Shasha Zhang ◽  
Ying Dong ◽  
Ruiying Qiang ◽  
Yuan Zhang ◽  
Xiaoli Zhang ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Immunofluorescent Staining ◽  
Cochlear Hair Cells ◽  
Interacting Protein ◽  
Hearing Ability ◽  
Hearing Function ◽  
Mrna And Protein Expression ◽  
And Function

Striatin-interacting protein 1 (Strip1) is a core component of the striatin interacting phosphatase and kinase (STRIPAK) complex, which is involved in embryogenesis and development, circadian rhythms, type 2 diabetes, and cancer progression. However, the expression and role of Strip1 in the mammalian cochlea remains unclear. Here we studied the expression and function of Strip1 in the mouse cochlea by using Strip1 knockout mice. We first found that the mRNA and protein expression of Strip1 increases as mice age starting from postnatal day (P) 3 and reaches its highest expression level at P30 and that the expression of Strip1 can be detected by immunofluorescent staining starting from P14 only in cochlear HCs, and not in supporting cells (SCs). Next, we crossed Strip1 heterozygous knockout (Strip +/−) mice to obtain Strip1 homozygous knockout (Strip1−/−) mice for studying the role of Strip1 in cochlear HCs. However, no Strip1−/− mice were obtained and the ratio of Strip +/− to Strip1+/+ mice per litter was about 2:1, which suggested that homozygous Strip1 knockout is embryonic lethal. We measured hearing function and counted the HC number in P30 and P60 Strip +/− mice and found that they had normal hearing ability and HC numbers compared to Strip1+/+ mice. Our study suggested that Strip1 probably play important roles in HC development and maturation, which needs further study in the future.

Characterization of anEscherichia coliSulfite Oxidase Homologue Reveals the Role of a Conserved Active Site Cysteine in Assembly and Function†

Biochemistry ◽  
2005 ◽  
Vol 44 (30) ◽  
pp. 10339-10348 ◽  
Author(s):  
Stephen J. Brokx ◽  
Richard A. Rothery ◽  
Guijin Zhang ◽  
Derek P. Ng ◽  
Joel H. Weiner
Keyword(s):  
Active Site ◽  
Active Site Cysteine ◽  
And Function

Role of Telomerase in Normal and Cancer Cells

2000 ◽  
Vol 18 (13) ◽  
pp. 2626-2634 ◽  
Author(s):  
Matthew Meyerson
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Detection ◽  
Telomeric Dna ◽  
Telomerase Inhibitors ◽  
Cell Immortalization ◽  
Detection And Diagnosis ◽  
And Function ◽  
Experimental Use

ABSTRACT: Shortening of the telomeric DNA at chromosome ends is postulated to limit the lifespan of human cells. In contrast, activation of telomerase, the enzyme that synthesizes telomeric DNA, is proposed to be an essential step in cancer cell immortalization and cancer progression. This review discusses the structure and function of telomeres and telomerase, the role of telomerase in cell immortalization, and the effects of telomerase inactivation on normal and cancer cells. Moreover, data on the experimental use of telomerase assays for cancer detection and diagnosis are reviewed. Finally, the review considers the evidence regarding whether telomerase inhibitors could be used to treat human cancers.

scholarly journals To form and function: on the role of basement membrane mechanics in tissue development, homeostasis and disease

Open Biology ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 200360
Author(s):  
Nargess Khalilgharibi ◽  
Yanlan Mao
Keyword(s):  
Basement Membrane ◽  
Molecular Mechanisms ◽  
Disease Diagnosis ◽  
Membrane Mechanics ◽  
Form And Function ◽  
And Function ◽  
Tissue Form

The basement membrane (BM) is a special type of extracellular matrix that lines the basal side of epithelial and endothelial tissues. Functionally, the BM is important for providing physical and biochemical cues to the overlying cells, sculpting the tissue into its correct size and shape. In this review, we focus on recent studies that have unveiled the complex mechanical properties of the BM. We discuss how these properties can change during development, homeostasis and disease via different molecular mechanisms, and the subsequent impact on tissue form and function in a variety of organisms. We also explore how better characterization of BM mechanics can contribute to disease diagnosis and treatment, as well as development of better in silico and in vitro models that not only impact the fields of tissue engineering and regenerative medicine, but can also reduce the use of animals in research.

scholarly journals Hyperactive Neutrophils Infiltrate Vital Organs of Tumor Bearing Host and Contribute to Gradual Systemic Deterioration With Tumor Progression

2021 ◽  
Author(s):  
Kavita Rawat ◽  
Saima Syeda ◽  
Anju Shrivastava
Keyword(s):  
Tumor Progression ◽  
Cancer Progression ◽  
Neutrophil Count ◽  
Mice Model ◽  
Potential Therapeutic Target ◽  
Tumor Bearing ◽  
Systemic Impact ◽  
And Function ◽  
High Infiltration

Various studies have addressed the role of neutrophils in cancer wherein the focus has been drawn on the elevated neutrophil count in blood or at tumor loci. However, cancer has a systemic impact which targets various organs thus challenging the overall physiology of the host. So, it is worthwhile to explore whether and how neutrophils contribute to systemic deterioration in cancer. To discern the systemic role of neutrophils, we monitored their number and function at different stages of tumor growth in Dalton’s lymphoma mice model. Notably, we observed a gradual increase in neutrophil count in blood and their infiltration in vital organs of tumor bearing mice. In parallel, we observed damaged histoarchitecture with significant alterations in biochemical parameters that aggravated with tumor progression. We next examined systemic impact of neutrophil by assessing neutrophil elastase, myeloperoxidase, and matrix metalloproteinases (MMP-8 and MMP-9) wherein we found their upregulated expression and activity in tumor condition. Taken together, our results demonstrate high infiltration and hyperactivation of neutrophils which possibly account for gradual systemic deterioration during cancer progression. Our findings thus implicate neutrophils as a potential therapeutic target that may help to reduce the overall fatality rate of cancer.

scholarly journals The semantics of microglia activation: neuroinflammation, homeostasis, and stress

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Samuel C. Woodburn ◽  
Justin L. Bollinger ◽  
Eric S. Wohleb
Keyword(s):  
Microglia Activation ◽  
Immune Functions ◽  
Neuronal Function ◽  
Stress Effects ◽  
Pathological Conditions ◽  
Microglial Phenotype ◽  
And Function ◽  
And Behavior

AbstractMicroglia are emerging as critical regulators of neuronal function and behavior in nearly every area of neuroscience. Initial reports focused on classical immune functions of microglia in pathological contexts, however, immunological concepts from these studies have been applied to describe neuro-immune interactions in the absence of disease, injury, or infection. Indeed, terms such as ‘microglia activation’ or ‘neuroinflammation’ are used ubiquitously to describe changes in neuro-immune function in disparate contexts; particularly in stress research, where these terms prompt undue comparisons to pathological conditions. This creates a barrier for investigators new to neuro-immunology and ultimately hinders our understanding of stress effects on microglia. As more studies seek to understand the role of microglia in neurobiology and behavior, it is increasingly important to develop standard methods to study and define microglial phenotype and function. In this review, we summarize primary research on the role of microglia in pathological and physiological contexts. Further, we propose a framework to better describe changes in microglia1 phenotype and function in chronic stress. This approach will enable more precise characterization of microglia in different contexts, which should facilitate development of microglia-directed therapeutics in psychiatric and neurological disease.

scholarly journals DsbA-L protects against diabetic renal injury through the adipo-renal axis

2021 ◽  
Author(s):  
Lingfeng Zeng ◽  
Ming Yang ◽  
Chun Hu ◽  
Li Zhao ◽  
Xianghui Chen ◽  
...  
Keyword(s):  
Renal Injury ◽  
Kidney Tissue ◽  
Normal Control Group ◽  
Control Group ◽  
Diabetic Mice ◽  
Urine Protein ◽  
Interacting Protein ◽  
Protein Levels ◽  
Mrna And Protein Expression

AbstractDisulfide-bond A oxidoreductase-like protein (DsbA-L) is an adiponectin-interacting protein that is highly expressed in adipose tissue. The adipo-renal axis involves adipocyte release of signaling molecules that are recruited to kidney and regulate kidney function. We have found that the DsbA-L modulated the progression of diabetic nephropathy, but the precise mechanism of this modulation is unknown. Here, the transgenic mice overexpressing DsbA-L protein in fat (fDsbA-L) were used to verify that the renoprotective role of DsbA-L whether by adipo-renal axis. Mice were divided into four groups: a normal (Control) group, STZ induced diabetic mice, fDsbA-L mice and diabetic fDsbA-L mice (n=6). Diabetes was induced in mice by STZ 100mg/kg and continued HFD feeding for 12 weeks. Compared with the control group, the weight, blood glucose,and urine protein levels and the pathological changes in the kidney tissue of diabetic mice were increased significantly, accompanied by increased NLRP3,caspase-1, IL-1β, IL-18, FN, and Collagen1 mRNA and protein expression, which were reduced in diabetic fDsbA-L mice. Interestingly, the level of adiponectin in serum and kidney expression in diabetic mice was reduced significantly compared to that in the control group. However this change was reversed in diabetic fDsbA-L mice. These data suggest that the overexpression of DsbA-L in the adipocytes of mice can protect against diabetic renal injury through anti-inflammatory mediators,and may be mediated by the adipo-renal axis.

scholarly journals Cancer-Associated Fibroblasts in Oral Cancer: A Current Perspective on Function and Potential for Therapeutic Targeting

2021 ◽  
Vol 2 ◽  
Author(s):  
Kamila J. Bienkowska ◽  
Christopher J. Hanley ◽  
Gareth J. Thomas
Keyword(s):  
Oral Cancer ◽  
Cancer Progression ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Tumour Microenvironment ◽  
Cancer Associated Fibroblasts ◽  
Current Perspective ◽  
And Function ◽  
Exciting Development

The role of the tumour microenvironement (TME) in cancer progression and resistance to therapies is now widely recognized. The most prominent non-immune cell type in the microenvironment of oral cancer (OSCC) is cancer-associated fibroblasts (CAF). Although CAF are a poorly characterised and heterogenous cell population, those with an “activated” myofibroblastic phenotype have been shown to support OSCC progression, promoting growth, invasion and numerous other “hallmarks of malignancy.” CAF also confer broad resistance to different types of therapy, including chemo/radiotherapy and EGFR inhibitors; consistent with this, CAF-rich OSCC are associated with poor prognosis. In recent years, much CAF research has focused on their immunological role in the tumour microenvironment, showing that CAF shield tumours from immune attack through multiple mechanisms, and particularly on their role in promoting resistance to anti-PD-1/PD-L1 checkpoint inhibitors, an exciting development for the treatment of recurrent/metastatic oral cancer, but which fails in most patients. This review summarises our current understanding of CAF subtypes and function in OSCC and discusses the potential for targeting these cells therapeutically.

scholarly journals A GIPC1-Palmitate Switch Modulates Dopamine Drd3 Receptor Trafficking and Signaling

2016 ◽  
Vol 36 (6) ◽  
pp. 1019-1031 ◽  
Author(s):  
Margarita Arango-Lievano ◽  
Ozge Sensoy ◽  
Amélie Borie ◽  
Maithé Corbani ◽  
Gilles Guillon ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Signaling Proteins ◽  
Interacting Protein ◽  
Mutant Proteins ◽  
C Terminus ◽  
Biased Signaling ◽  
Dopamine D3 ◽  
Dynamics Simulations

Palmitoylation is involved in several neuropsychiatric and movement disorders for which a dysfunctional signaling of the dopamine D3 receptor (Drd3) is hypothesized. Computational modeling of Drd3's homologue, Drd2, has shed some light on the putative role of palmitoylation as a reversible switch for dopaminergic receptor signaling. Drd3 is presumed to be palmitoylated, based on sequence homology with Drd2, but the functional attributes afforded by Drd3 palmitoylation have not been studied. Since these receptors are major targets of antipsychotic and anti-Parkinsonian drugs, a better characterization of Drd3 signaling and posttranslational modifications, like palmitoylation, may improve the prospects for drug development. Using molecular dynamics simulations, we evaluatedin silicohow Drd3 palmitoylation could elicit significant remodeling of the C-terminal cytoplasmic domain to expose docking sites for signaling proteins. We tested this modelin celluloby using the interaction of Drd3 with the G-alpha interacting protein (GAIP) C terminus 1 (GIPC1) as a template. From a series of biochemical studies, live imaging, and analyses of mutant proteins, we propose that Drd3 palmitoylation acts as a molecular switch for Drd3-biased signaling via a GIPC1-dependent route, which is likely to affect the mode of action of antipsychotic drugs.

scholarly journals Regulation of Breast Cancer and Bone Metastasis by MicroRNAs

2013 ◽  
Vol 35 ◽  
pp. 369-387 ◽  
Author(s):  
S. Vimalraj ◽  
P. J. Miranda ◽  
B. Ramyakrishna ◽  
N. Selvamurugan
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Bone Metastasis ◽  
Cancer Progression ◽  
Human Breast ◽  
Protein Coding ◽  
Regulate Gene Expression ◽  
Complex Process ◽  
And Function

Breast cancer progression including bone metastasis is a complex process involving numerous changes in gene expression and function. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that regulate gene expression by targeting protein-coding mRNAs posttranscriptionally, often affecting a number of gene targets simultaneously. Alteration in expression of miRNAs is common in human breast cancer, possessing with either oncogenic or tumor suppressive activity. The expression and the functional role of several miRNAs (miR-206, miR-31, miR-27a/b, miR-21, miR-92a, miR-205, miR-125a/b, miR-10b, miR-155, miR-146a/b, miR-335, miR-204, miR-211, miR-7, miR-22, miR-126, and miR-17) in breast cancer has been identified. In this review we summarize the experimentally validated targets of up- and downregulated miRNAs and their regulation in breast cancer and bone metastasis for diagnostic and therapeutic purposes.

scholarly journals Detailed structural and biochemical characterization of the nexin-dynein regulatory complex

2015 ◽  
Vol 26 (2) ◽  
pp. 294-304 ◽  
Author(s):  
Toshiyuki Oda ◽  
Haruaki Yanagisawa ◽  
Masahide Kikkawa
Keyword(s):  
Biochemical Characterization ◽  
Electron Tomography ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Dynein Motor ◽  
Cryo Electron Tomography ◽  
Regulatory Complex ◽  
And Function

The nexin-dynein regulatory complex (N-DRC) forms a cross-bridge between the outer doublet microtubules of the axoneme and regulates dynein motor activity in cilia/flagella. Although the molecular composition and the three-dimensional structure of N-DRC have been studied using mutant strains lacking N-DRC subunits, more accurate approaches are necessary to characterize the structure and function of N-DRC. In this study, we precisely localized DRC1, DRC2, and DRC4 using cryo–electron tomography and structural labeling. All three N-DRC subunits had elongated conformations and spanned the length of N-DRC. Furthermore, we purified N-DRC and characterized its microtubule-binding properties. Purified N-DRC bound to the microtubule and partially inhibited microtubule sliding driven by the outer dynein arms (ODAs). Of interest, microtubule sliding was observed even in the presence of fourfold molar excess of N-DRC relative to ODA. These results provide insights into the role of N-DRC in generating the beating motions of cilia/flagella.

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