EDITOR’S CHOICE Proteins: a brief look in the literature


Following the review of p53 protein in last month’s issue of The Biomedical Scientist (page 175), Brian Nation selects a small sample of protein research to be found in the current literature.


Cancer antigen 125 (CA125, MUC16) protein expression in the diagnosis and progression of pancreatic ductal adenocarcinoma. Jiang K, Tan E, Sayegh Z, Centeno B, Malafa M, Coppola D. Appl Immunohistochem Mol Morphol 2016 Apr 16 (Epub ahead of print).


Pancreatic ductal adenocarcinoma (PDAC) is an aggressive carcinoma, with most patients diagnosed at an advanced stage, with a five- year survival rate of around 5%. Clearly, identifying better diagnostic, prognostic and therapeutic markers for this lethal disease is needed urgently. Recently, CA125 has been identified in


PDAC, and the aim of this research was to study the changes in CA125 expression during the progression of benign pancreatic tissue (BPT) to PDAC, and to assess its value as a biomarker of tumour growth. To address these questions, cellular levels of CA125 in BPT and PDAC were measured using immuno- histochemistry and compared on the basis of tumour staging and tissue microarray technology constructed using resected pancreatic tissues. The staining reactions for each case were evaluated semiquantitatively using the histological score system. The investigation demonstrated a consistent


and significant upregulation of CA125 during the transition from BPT to PDAC. The authors also found a direct correlation between CA125 immunohistochemistry score and tumour stage (P=0.02). In conclusion, the data indicated that CA125 plays a direct role in pancreatic carcinogenesis and suggests that it may be used as a diagnostic and/or prognostic biomarker of pancreatic cancer.


Investigating CFTR and KCa3.1 protein/ protein interactions. Klein H, Abu-Arish A, Trinh NT et al. PLoS One 2016; 11 (4): e0153665.


In epithelia, Cl– channels play a prominent role


in fluid and electrolyte transport. Of particular importance is the cAMP-dependent cystic fibrosis transmembrane conductance regulator Cl–


channel (CFTR) with mutations of


the CFTR encoding gene causing cystic fibrosis. The bulk transepithelial transport of Cl– ions and electrolytes needs to be coupled to an increase in K+


conductance in order to recycle K+ and maintain an electrical driving force for


anion exit across the apical membrane. In this study, the authors showed that CFTR


and KCa3.1 can interact. A two-hybrid screen was performed to identify which KCa3.1 cytosolic domains might mediate an interaction with CFTR. The results showed that both the N-terminal fragment M1-M40 of KCa3.1 and part of the KCa3.1 calmodulin binding domain (residues L345–A400) interact with the NBD2 segment (G1237–Y1420) and C-region of CFTR (residues T1387–L1480), respectively. An association of CFTR and F508del-CFTR with KCa3.1 was confirmed in co-immuno- precipitation experiments demonstrating the formation of immuno-precipitable CFTR/ KCa3.1 complexes in CFBE cells. Evidence was presented through cross-


correlation spectroscopy measurements that KCa3.1 and CFTR co-localise at the plasma membrane and that KCa3.1 channels tend to aggregate as a result of an enhanced interaction with CFTR channels at the plasma membrane following an increase in


Architecture, Function, and Genomics A M Lesk, Oxford: Oxford University Press, 2016. ISBN: 9780198716846. 488 pp. £39.99 (Paperback).


A further edition (the third) in this respected series in a relatively short time period reflects the impact of new developments particularly in bioinformatics with a number of accessible new data banks of amino acids, proteins and structures, and the increased interest in molecular evolution. This is a well- structured and comprehensive textbook which often achieves more depth than the introductory title would suggest. Each chapter includes clearly defined


learning goals, useful summary and additional information ‘boxes’ and exercises,


THE BIOMEDICAL SCIENTIST MAY 2016


which are web-linked, to challenge the reader. The text is well presented and the figures are often visually stunning and are used to good effect in the understanding of structure and its relevance to physiological function. This textbook is highly


recommended for those with a special interest in proteins or working in protein research. Biomedical scientists will find this textbook interesting and a stimulating source of


knowledge of the role of proteins in health and disease, such as in a number of genetic and immunological conditions. The basic principles of protein-related techniques are clearly described, including mass spectrometry and various forms of chromatography and electrophoresis. The closing chapter provides an excellent introduction to genomics,


proteomics and the methods used in systems biology.


S Clarke 271 Introduction to Protein Science: intracellular Ca2+ concentration. The results


suggest that the physical interaction KCa3.1/ CFTR can occur early during the biogenesis of both proteins, and that KCa3.1 and CFTR form a dynamic complex, the formation of which depends on internal Ca2+


.


Maternal mid-pregnancy C-reactive protein and risk of autism spectrum disorders: the early markers for autism study. Zerbo O1, Traglia M2, Yoshida Cet al. Transl Psychiatry 2016 Apr 19; 6: e783.


Maternal pregnancy levels of the inflammatory marker C-reactive protein (CRP) has been associated with autism spectrum disorder (ASD) in the offspring. A population-based, nested case-control study with 500 children with ASD, 235 with developmental delay (DD) and 580 general population (GP) controls was performed to investigate whether elevated CRP during pregnancy increases the risk of ASD. Maternal CRP concentration was measured in archived serum collected at 15–19 weeks of pregnancy and genome-wide SNP data were generated. The levels of CRP were compared between


ASD vs.GP and DD vs.GP. The genetic associations with CRP were assessed via linear regression. Maternal CRP levels in mid- pregnancy were lower in mothers of ASD infants compared with controls. The maternal CRP levels in the upper third and fourth quartiles were associated with a 45% and 44% decreased risk of ASD, respectively. Two SNPs at the CRP locus showed strong association with CRP levels but were not associated with ASD. No difference was found between maternal


CRP levels of DD and controls. The reasons for the lower levels of CRP in mothers are not known but may be related to alterations in the immune response to infectious agents.


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