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Order Lefavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
Besides their use as the previously described display tools, the baculoviruses served as the source of polyhedrin, which could be regarded as a special class of highly structured carriers. As mentioned briefly earlier, the polyhedrin is synthesized in massive amounts and forms a protective crystal around the viruses, which allows them to remain viable for many years outside the insect larvae (Rohrmann 1986). The x-ray crystallographic examination of polyhedrins started in early 1980s (Rohrmann 1986). The chimeric AcMNPV polyhedrin proteins carrying an influenza hemagglutinin epitope not only showed influenza-specific antigenic and immunogenic properties but also presented the foreign epitope on the surface of the chimeric occlusion bodies (McLinden et al. 1992). Furthermore, chimeras of the AcMNPV polyhedrin and Trichoplusia ni granulosis virus (TnGV) granulin were constructed (Eason et al. 1998). The results clearly showed that the size and structure of occlusions was affected by the primary structure of the product, although the involvement of other viral proteins in the virion occlusion body assembly and shape complicated interpretation and further application of this system (Chen et al. 2013).
Genetics and genomics of idiopathic pulmonary fibrosis
Published in Muhunthan Thillai, David R Moller, Keith C Meyer, Clinical Handbook of Interstitial Lung Disease, 2017
Susan K Mathai, David A Schwartz
Another study by Meltzer and colleagues examined microarray data utilizing RNA from peripheral whole blood to derive a 108-gene signature to distinguish IPF from normal controls (17) that had a sensitivity of 70% and specificity of 100% (accuracy 77%), though was not useful in predicting disease severity. Notable genes highlighted in this analysis included granulin (GRN) and matrix metalloprotease 9 (MMP9), a gene whose protein product has been implicated in prior studies of IPF (17,58).
Parasite Versus Host: Pathology and Disease
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2015
Eric S. Loker, Bruce V. Hofkin
In some cases, parasite-induced pathology is merely an unfortunate by-product of the infection that is of no obvious adaptive value to the parasite. Opisthorchis viverrini, for example, commonly called the Southeast Asian liver fluke, is a digenetic trematode that as an adult inhabits the bile duct of its mammalian definitive host. Chronic infections may lead to a cancer of the bile duct known as cholangiocarcinoma. It is not entirely clear how the trematode predisposes an infected individual to this type of cancer. Mechanical damage caused by the fluke, inflammation in response to secreted fluke antigens, or both, may be involved in setting the stage for carcinogenesis. OV-GRN-1,a secreted parasite protein with considerable sequence similarity to the mammalian growth factor granulin, may be particularly important. Provoking cancer in its host provides no benefit to the fluke. Cholangiocarcinoma is simply a side effect of an O. viverrini infection.
Peptidomics and proteogenomics: background, challenges and future needs
Published in Expert Review of Proteomics, 2021
Rui Vitorino, Manisha Choudhury, Sofia Guedes, Rita Ferreira, Visith Thongboonkerd, Lakshya Sharma, Francisco Amado, Sanjeeva Srivastava
In one study, urine samples were used to detect biomarkers for hepatocellular carcinoma (HCC), a highly aggressive cancer [141]. In the study, an onco-proteogenomics approach was used to obtain protein expression profiles, and S100A9 and granulin were identified as immunobiomarkers whose expression was elevated in cancer. These cancer-specific biomarkers are known to play an important role in tumor development and cancer metastasis [141]. In another study, a shotgun proteomics approach based on nano-liquid chromatography coupled with tandem mass spectrometry (nanoLC-MS/MS) was used to identify HCC biomarkers from urine, and labeling was performed with the stable isotope dimethyl. This approach also identified S100A9 and granulin as potential biomarkers for HCC [142]. Urinary peptidome analysis has also been used as a resource for identifying prognostic biomarkers for bladder cancer recurrence and renal cell carcinoma [143,144]. Quantitative label-free liquid chromatography-tandem mass spectrometry-peptidomics method has been used to identify biomarkers for early detection of renal cell carcinoma.
Progranulin as a therapeutic target for dementia
Published in Expert Opinion on Therapeutic Targets, 2018
Daniela Galimberti, Chiara Fenoglio, Elio Scarpini
Progranulin (PGRN) was identified as an acrosomal glycoprotein (named acrogranin) synthesized during spermatogenesis in 1990 [1]. The gene encoding for PGRN (GRN), is localized on chromosome 17q21.32, and contains 12 exons, which results in 3 isoforms [2]. PGRN consists of 593 amino acids and has a molecular weight of 68.5 kDa [3]. The protein has emerged as the prototypic member of a family of structurally unique proteins, evolutionarily conserved, related to growth factors [4]. Full-length PGRN consists of a secretory N-terminal signal peptide of 17 amino acids, and 7.5 granulin domains. Granulins are named, from the N to the C terminus: granulins p (paragranulin domain), G, F, B, A, C, D, and E. Granulin domains are composed of tandem repeats of a 12-cysteine motif (see [5] for details on the molecular structure of the protein). PGRN can be cleaved into granulins by serine and threonine proteases, such as metalloproteinases and elastase. On the other hand, Secretory Leukocytes Protease Inhibitor can bind directly to PGRN, blocking the proteolysis by elastase. Both PGRN and granulins are biologically active, although often with opposing actions. Whereas PGRN has anti-inflammatory properties, granulins display proinflammatory properties. Regarding cell growth, PGRN is a mitogenic and is overexpressed in tumors, whereas the different granulin peptides may have growth-promoting or growth-inhibiting activities, although they seem to act with lower potency than PGRN. Therefore, PGRN-granulins balance is critical in a number of biological processes.
Are early follicular phase serum progranulin levels predictive of the response to ovarian stimulation in IVF cycles?
Published in Human Fertility, 2022
Ebru Ersoy, Nafiye Yilmaz, Aytekin Tokmak
Like other ovarian reserve markers, PGRN did not predict pregnancy success. Owing to this lack of an association, PGRN alone may not be used to assess the ovarian reserve. However, it may still play a role in the physiological and pathological processes of ovarian folliculogenesis and may be combined with AMH and AFC in the prediction of ovarian response. Because a recent study revealed that granulin, which is the cleavage product of PGRN, is found at significantly lower levels in patients with premature ovarian failure, it may have a role in the pathophysiology of this disease (Ersoy et al., 2015).