CREP Summer Journal Club Purpose of Summer Journal
CREP Summer Journal Club
Purpose of Summer Journal Club • Read analyze scientific literature • Discussion to increase understanding • Build oral presentation skills Schedule • 5 meetings • Noon-1 pm; B 1 classroom
Picking your article • Ask mentor or lab mates for suggestions • Literature search • Primary article (no reviews) • Basic research, case study, clinical trial • Keep it simple (6 -8 figures) • Avoid journals like Science • Send article to me for distribution (72 hr before presentation) • Looking for 40 -45 minute presentation/discussion
What’s in a scientific paper and how do you talk about it? • Abstract • Brief summary of paper • Concise statements of what was done and outcome • Introduction • Background for work (what others have done) • Frames the problem (what do we still need to know) Don’t mention Provide audience enough of the background so they can understand why this area is important • Materials & Methods • Describes assays/methods used to conduct study • Results • What were the outcomes of the work • Discussion • Interpretation of results • Puts data in context of field (did study fill a knowledge void) Spend most of the discussion here
Things to consider as you read and discuss your article • Look up unfamiliar terms • Read introduction (and conclusion) first • Read with an open mind and critical eye • The author should convince you (with data) that their conclusion is correct
Plasma levels of soluble fibroblast activation protein in arterial thrombosis: determinants and cleavage of its substrate a-2 antiplasmin Uitte de Willige et al. , Int J Cardiol 178 (2015) 105 -110.
Why are we interested in FAP?
Fibroblast Activation Protein (FAP) • Serine protease • Cleaves after Pro residues • Homodimer • Typically transmembrane • Can be present in soluble form • Can cleave a variety of proteins • • Collagen type I a-2 -antiplasmin FGF-21 Several neuropeptides (BNP, substance P)
The goal of this study is to look at s. FAP levels in patients with arterial thrombosis
Patient Population – retrospective study • Eligibility criteria • First arterial thrombotic event (cardiac, cerebral, peripheral) • <45 yrs (male) or <55 yrs (female) • Total of 633 patients (coronary heart disease – CHD; ischemic stroke – IS; peripheral arterial disease – PAD) • Most have risk factors/medications compared to control group • All provided written informed consent
Correlation coefficients • A number that represents the dependence or statistical relationship between two or more values • Pearson (r) – measure of the strength and direction of a linear relationship between 2 variables • Spearman (rho) – how well the relationship between two variables can be described using a monotonic function (doesn’t have to be linear)
s. FAP levels don’t change significantly with disease • Measured serum s. FAP levels by ELISA – no significant differences • For CHD patients • If they looked at time of inclusion in study after event and s. FAP; significant correlation (p=0. 013) • s. FAP levels increased Time between event and study inclusion (CHD patients) They don’t have appear to included the control group in the plot
a 2 AP levels are different in CHD patients • Total a 2 AP levels didn’t change with any of the patient groups • When they looked at specific products • Significant increase in Met-a 2 AP in CHD and IS patients • This means significantly less cleavage
And more correlations……. in healthy controls • With a large enough sample size, you will get correlations but do they really mean anything?
Take home points • In CHD patients, s. FAP levels declined after thrombolytic event but increase over time • Patients in this study were enrolled 1 -3 months after the event so levels are decreased for some time • This agrees with findings in acute coronary events or in patients with stable CAD • Don’t know how this compares to tissue FAP levels or if circulating levels reflect tissue expression • Reduced cleavage of a 2 AP due to reduced s. FAP • What if something else cleaves a 2 AP? • “This indicates that it is likely that s. FAP regulates this cleavage in vivo and that a 2 AP is indeed a physiological substrate of s. FAP”. – not so fast
Limitations • Nature of patient population • • Survival bias Longer time after event for IS and PAD patients Medications Restriction to look at only a 2 AP(R 6) homozygous individuals • There is a Trp/Arg polymorphism at this position but the antibody used in their detection assay only recognizes Arg at position 6 (the Arg allele has a frequency of 80%)
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