Gears-In-Motion: The Interplay of WW and PPIase Domains in Pin1

Pin1 belongs to the family of the peptidyl-prolyl cis-trans isomerase (PPIase), which is a class of enzymes that catalyze the cis/trans isomerization of the Proline residue. Pin1 is unique and only catalyzes the phosphorylated Serine/Threonine-Proline (S/T-P) motifs of a subset of proteins. Since the discovery of Pin1 as a key protein in cell cycle regulation, it has been implicated in numerous diseases, ranging from cancer to neurodegenerative diseases. The main features of Pin1 lies in its two main domains: the WW (two conserved tryptophan) domain and the PPIase domain. Despite extensive studies trying to understand the mechanisms of Pin1 functions, how these two domains contribute to the biological roles of Pin1 in cellular signaling requires more investigations. The WW domain of Pin1 is known to have a higher affinity to its substrate than that of the PPIase domain. Yet, the WW domain seems to prefer the trans configuration of phosphorylated S/T-P motif, while the PPIase catalyzes the cis to trans isomerasion. Such contradicting information has generated much confusion as to the actual mechanism of Pin1 function. In addition, dynamic allostery has been suggested to be important for Pin1 function. Henceforth, in this review, we will be looking at the progress made in understanding the function of Pin1, and how these understandings can aid us in overcoming the diseases implicated by Pin1 such as cancer during drug development

Physical and Chemical Characterization of Rice Using Microwave and Laboratory Methods

Two main species of cultivated rice in the world are Oryza sativa (Asian rice) and Oryza glaberrima (African rice). The Oryza sativa species, which is grown worldwide, is far more widely utilized compared with the Oryza glaberrima species, which is grown in West Africa. Recently, the annual rice production has reached almost 480 million tonnes, and this demand is expected to rise to 550 million tonnes in 2035. Thus, this increases the need to characterize and maintain the quality of rice and hence to determine the price of rice appropriately. Obviously, modern technologies that can provide fast and accurate measurement are essential in the large-scale industrial rice processing. In this chapter, several technologies and instruments used for rice processing are reviewed. The principle of the measurement for each technology is briefly described. The strength of this chapter is to introduce the application of microwave technology during rice processing, such as rice dying process, rice moisture detection, broken rice measurement and rice insect control. The pros and cons of the microwave method will be discussed in detail. Hence, some standard test laboratory for monitoring of carbohydrate, protein, fat and trace elements content is also described in this chapter

Dramatic Improvement of Proteomic Analysis of Zebrafish Liver Tumor by Effective Protein Extraction with Sodium Deoxycholate and Heat Denaturation

Majority of the proteomic studies on tissue samples involve the use of gel-based approach for profiling and digestion. The laborious gel-based approach is slowly being replaced by the advancing in-solution digestion approach. However, there are still several difficulties such as difficult-to-solubilize proteins, poor proteomic analysis in complex tissue samples, and the presence of sample impurities. Henceforth, there is a great demand to formulate a highly efficient protein extraction buffer with high protein extraction efficiency from tissue samples, high compatibility with in-solution digestion, reduced number of sample handling steps to reduce sample loss, low time consumption, low cost, and ease of usage. Here, we evaluated various existing protein extraction buffers with zebrafish liver tumor samples and found that sodium deoxycholate- (DOC-) based extraction buffer with heat denaturation was the most effective approach for highly efficient extraction of proteins from complex tissues such as the zebrafish liver tumor. A total of 4,790 proteins have been identified using shotgun proteomics approach with 2D LC, which to our knowledge is the most comprehensive study for zebrafish liver tumor proteome

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

THE BIO-MOLECULAR ANALYSIS OF TITANIUM DIOXIDE NANOPARTICLES EXPOSURE ON CARDIOMYOCYTES

Ph.DDOCTOR OF PHILOSOPHY (FOS

The redox language in neurodegenerative diseases: oxidative post-translational modifications by hydrogen peroxide

10.1038/s41419-020-03355-3Cell Death and Disease1215

Optimal management of upper tract urothelial carcinoma : current perspectives

Introduction: Upper tract urothelial carcinoma (UTUC) is a relatively uncommon urologic malignancy for which there has not been significant improvement in survival over the past few decades, highlighting the need for optimal multi-modality management. Methods: A non-systematic review of the latest literature was performed to include relevantarticles up to June 2019. It summarizes the epidemiologic risk factors associated with UTUC,including smoking, carcinogenic aromatic amines, arsenic, aristolochic acid, and Lynchsyndrome. Molecular pathways underlying UTUC and potential druggable targets are outlined. Results: Surgical management for UTUC includes kidney-sparing surgery (KSS) for low-risk disease and radical nephroureterectomy (RNU) for high-risk disease. Endoscopic man-agement of UTUC may include ureteroscopic or percutaneous resection. Topical instillationtherapy post-KSS aims to reduce recurrence, progression and to treat carcinoma-in-situ; thismay be achieved retrogradely (via ureteric catheterization), antegradely (via percutaneousnephrostomy) or via reflux through double-J stent. RNU, which may be performed via open,laparoscopic or robot-assisted approaches, is the gold standard treatment for high-riskUTUC. The distal cuff may be dealt with extravesical, transvesical or endoscopic techniques.Peri-operative chemotherapy and immunotherapy are increasingly utilized; level 1 evidenceexists for adjuvant chemotherapy, but neoadjuvant chemotherapy is favored as kidneyfunction is better prior to RNU. Immunotherapy is primarily reserved for metastatic UTUCbut is currently being investigated in the perioperative setting. Conclusion: The optimal management of UTUC includes afirm understanding of theepidemiological factors and molecular pathways. Surgical management includes KSS forlow-risk disease and RNU for high-risk disease. Peri-operative immunotherapy and che-motherapy may be considered as evidence mounts.Published versio