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Amy Brown, Intekhab Hossain, Lester J. Perez, Carine Nzirorera, Kathleen Tozer, Kenneth D’Souza, Purvi C. Trivedi, Christie Aguiar, Alexandra M. Yip, Jennifer Shea, Keith R. Brunt, Jean-Francois Legare, Ansar Hassan, Thomas Pulinilkunnil, Petra C. Kienesberger
Lysophosphatidic acid receptor mRNA levels in heart and white adipose tissue are associated with obesity in mice and humans
www.plosone.org
www.plosone.org
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10 0 0 10 200.0125 707.4141 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(cardiovascular)Tj
6.0037 0 Td
(morbidity)Tj
4.2349 0 Td
(in)Tj
1.0375 0 Td
(individuals)Tj
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(undergoing)Tj
4.8755 0 Td
(cardiac)Tj
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(surgery.)Tj
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(we)Tj
1.3266 0 Td
(show)Tj
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(a)Tj
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(detailed)Tj
-33.8057 -1.3039 Td
(characterization)Tj
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(of)Tj
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(the)Tj
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(mRNA)Tj
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(expression)Tj
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(patterns)Tj
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(of)Tj
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(known)Tj
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(bona)Tj
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(fide)Tj
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(LPA)Tj
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(receptors)Tj
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(in)Tj
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(the)Tj
-35.0813 -1.2982 Td
(myocardium)Tj
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(and)Tj
1.7348 0 Td
(adipose)Tj
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(tissue)Tj
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(of)Tj
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(humans)Tj
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(with)Tj
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(an)Tj
1.2019 0 Td
(examination)Tj
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(response)Tj
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(obesity,)Tj
3.2598 0 Td
(and)Tj
1.7348 0 Td
(determine)Tj
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(whether)Tj
3.4753 0 Td
(LPA)Tj
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(receptor)Tj
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(expression)Tj
4.4617 0 Td
(is)Tj
0.8504 0 Td
(correlated)Tj
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(to)Tj
1.0261 0 Td
(metabolic)Tj
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(parameters)Tj
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(and)Tj
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(outcomes)Tj
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(after)Tj
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(cardiac)Tj
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(surgery.)Tj
3.4185 0 Td
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1.6101 0 Td
(also)Tj
1.7688 0 Td
(show)Tj
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(LPA)Tj
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(receptor)Tj
3.5546 0 Td
(expression)Tj
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(in)Tj
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(heart)Tj
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(and)Tj
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(adi-)Tj
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(tissue)Tj
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(mice)Tj
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(and)Tj
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(cultured)Tj
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(cardiomyocytes)Tj
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(and)Tj
1.7292 0 Td
(adipocytes)Tj
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(to)Tj
1.0262 0 Td
(determine)Tj
4.3256 0 Td
(whether)Tj
3.4753 0 Td
(LPA)Tj
-35.6256 -1.2982 Td
(receptor)Tj
3.5546 0 Td
(regulation)Tj
4.3086 0 Td
(in)Tj
1.0375 0 Td
(response)Tj
3.7304 0 Td
(to)Tj
1.0261 0 Td
(obesogenic)Tj
4.6544 0 Td
(stimuli)Tj
3.0048 0 Td
(is)Tj
0.8503 0 Td
(comparable)Tj
4.9039 0 Td
(among)Tj
2.9934 0 Td
(humans)Tj
3.4356 0 Td
(and)Tj
1.7348 0 Td
(ani-)Tj
-35.2344 -1.2983 Td
(mal/cell)Tj
3.3902 0 Td
(models)Tj
3.101 0 Td
(of)Tj
1.0148 0 Td
(metabolic)Tj
4.1499 0 Td
(and)Tj
1.7292 0 Td
(cardiovascular)Tj
6.0037 0 Td
(disease)Tj
3.016 0 Td
(that)Tj
1.7802 0 Td
(are)Tj
1.4457 0 Td
(used)Tj
2.0636 0 Td
(for)Tj
1.3833 0 Td
(drug)Tj
2.1146 0 Td
(development)Tj
-31.1922 -1.3039 Td
(and)Tj
1.7291 0 Td
(preclinical)Tj
4.388 0 Td
(validation.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 576.0566 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Materials)Tj
4.5071 0 Td
(and)Tj
1.989 0 Td
(methods)Tj
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-6.4961 -1.5023 Td
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3.3874 0 Td
(sampling)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 541.0771 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(All)Tj
1.3946 0 Td
(protocols)Tj
3.9571 0 Td
(involving)Tj
3.9798 0 Td
(human)Tj
3.0785 0 Td
(subjects)Tj
3.3788 0 Td
(were)Tj
2.1203 0 Td
(approved)Tj
3.9742 0 Td
(by)Tj
1.1849 0 Td
(the)Tj
1.4683 0 Td
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3.8041 0 Td
(Ethics)Tj
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(Board)Tj
2.6362 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
-34.6618 -1.3039 Td
(Saint)Tj
2.245 0 Td
(John)Tj
2.1316 0 Td
(Regional)Tj
3.7304 0 Td
(Hospital,)Tj
3.8437 0 Td
(NB,)Tj
1.7632 0 Td
(Canada)Tj
3.2598 0 Td
(\(protocol)Tj
3.9401 0 Td
(#20142006\).)Tj
5.5843 0 Td
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3.3165 0 Td
(tissue)Tj
2.4548 0 Td
(samples)Tj
3.3845 0 Td
(were)Tj
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(collected)Tj
3.736 0 Td
(from)Tj
2.2053 0 Td
(patients)Tj
3.3732 0 Td
(undergoing)Tj
4.8699 0 Td
(elective,)Tj
3.4073 0 Td
(first-time)Tj
3.9628 0 Td
(cardiac)Tj
3.101 0 Td
(surgery)Tj
3.1975 0 Td
(\(coronary)Tj
4.1726 0 Td
(artery)Tj
2.5738 0 Td
(bypass)Tj
-34.5994 -1.2983 Td
(graft)Tj
2.0749 0 Td
(and/or)Tj
2.9367 0 Td
(valve)Tj
2.2337 0 Td
(surgery\))Tj
3.5376 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4683 0 Td
(New)Tj
2.0637 0 Td
(Brunswick)Tj
4.4787 0 Td
(Heart)Tj
2.5171 0 Td
(Centre)Tj
2.948 0 Td
(in)Tj
1.0375 0 Td
(Saint)Tj
2.2394 0 Td
(John,)Tj
2.3584 0 Td
(NB,)Tj
1.7631 0 Td
(Canada)Tj
3.2598 0 Td
(who)Tj
-35.8693 -1.3039 Td
(provided)Tj
3.8154 0 Td
(consent)Tj
3.3278 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(enrolled)Tj
3.5149 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4684 0 Td
(study.)Tj
2.6135 0 Td
(Immediately)Tj
5.2781 0 Td
(before)Tj
2.7382 0 Td
(surgery,)Tj
3.4186 0 Td
(a)Tj
0.6576 0 Td
(venous)Tj
3.0387 0 Td
(blood)Tj
2.5172 0 Td
(sam-)Tj
-35.6029 -1.2983 Td
(ple)Tj
1.4059 0 Td
(was)Tj
1.7008 0 Td
(collected.)Tj
3.9628 0 Td
(During)Tj
3.1351 0 Td
(the)Tj
1.4683 0 Td
(surgery,)Tj
3.4243 0 Td
(samples)Tj
3.3789 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(right)Tj
2.1486 0 Td
(atrial)Tj
2.2677 0 Td
(appendage)Tj
4.5127 0 Td
(\(AA\))Tj
2.2677 0 Td
(and)Tj
1.7292 0 Td
(thoracic)Tj
-33.8908 -1.2982 Td
(subcutaneous)Tj
5.6635 0 Td
(adipose)Tj
3.2599 0 Td
(tissue)Tj
2.4604 0 Td
(\(SAT\))Tj
2.6702 0 Td
(were)Tj
2.1203 0 Td
(excised,)Tj
3.3392 0 Td
(frozen)Tj
2.7723 0 Td
(in)Tj
1.0318 0 Td
(liquid)Tj
2.5625 0 Td
(nitrogen,)Tj
3.8778 0 Td
(and)Tj
1.7291 0 Td
(stored)Tj
2.7099 0 Td
(at)Tj
0.9524 0 Td
(-80C)Tj
-35.1493 -1.304 Td
(until)Tj
2.1089 0 Td
(further)Tj
3.0274 0 Td
(processing)Tj
4.4617 0 Td
(for)Tj
1.389 0 Td
(quantitative)Tj
4.9776 0 Td
(polymerase)Tj
4.7792 0 Td
(chain)Tj
2.4207 0 Td
(reaction)Tj
3.4923 0 Td
(\(qPCR\))Tj
3.2485 0 Td
(analysis)Tj
3.3278 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
1.8199 0 Td
(1)Tj
0 g
(\).)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 422.7023 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Experimental)Tj
5.9858 0 Td
(models)Tj
3.4063 0 Td
(of)Tj
1.0442 0 Td
(obesity)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 405.6944 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(All)Tj
1.3946 0 Td
(protocols)Tj
3.9571 0 Td
(involving)Tj
3.9798 0 Td
(mice)Tj
2.1544 0 Td
(were)Tj
2.1259 0 Td
(approved)Tj
3.9685 0 Td
(by)Tj
1.1849 0 Td
(the)Tj
1.4683 0 Td
(Dalhousie)Tj
4.252 0 Td
(University)Tj
4.3993 0 Td
(Institutional)Tj
5.1647 0 Td
(Animal)Tj
-34.0495 -1.2982 Td
(Care)Tj
2.1089 0 Td
(and)Tj
1.7348 0 Td
(Use)Tj
1.7405 0 Td
(Committee.)Tj
4.9606 0 Td
(Male)Tj
2.2166 0 Td
(C57BL/6J)Tj
4.0876 0 Td
(mice)Tj
2.1543 0 Td
(\(The)Tj
2.126 0 Td
(Jackson)Tj
3.3165 0 Td
(Laboratory\))Tj
4.9833 0 Td
(were)Tj
2.1259 0 Td
(housed)Tj
3.0898 0 Td
(on)Tj
1.2756 0 Td
(a)Tj
0.6576 0 Td
(12)Tj
-36.578 -1.3039 Td
(h)Tj
0.7483 0 Td
(light:)Tj
2.2507 0 Td
(12)Tj
1.1679 0 Td
(h)Tj
0.7483 0 Td
(dark)Tj
2.0523 0 Td
(cycle)Tj
2.1883 0 Td
(with)Tj
1.9956 0 Td
(ad)Tj
1.1849 0 Td
(libitum)Tj
3.1521 0 Td
(access)Tj
2.6475 0 Td
(to)Tj
1.0261 0 Td
(food)Tj
2.0466 0 Td
(and)Tj
1.7292 0 Td
(water.)Tj
2.6588 0 Td
(Eight)Tj
2.3471 0 Td
(week-old)Tj
3.8778 0 Td
(mice)Tj
2.1543 0 Td
(were)Tj
-33.9758 -1.2983 Td
(randomly)Tj
4.1272 0 Td
(assigned)Tj
3.6113 0 Td
(to)Tj
1.0204 0 Td
(cohorts)Tj
3.2202 0 Td
(fed)Tj
1.457 0 Td
(either)Tj
2.5341 0 Td
(chow)Tj
2.3585 0 Td
(\(5001,)Tj
2.6872 0 Td
(Lab)Tj
1.7008 0 Td
(Diet\))Tj
2.2847 0 Td
(or)Tj
1.0998 0 Td
(high)Tj
2.0069 0 Td
(fat-high)Tj
3.3789 0 Td
(sucrose)Tj
-31.487 -1.2983 Td
(\(HFHS\))Tj
3.4355 0 Td
(diet)Tj
1.7405 0 Td
(\(12451,)Tj
3.1634 0 Td
(Research)Tj
3.8041 0 Td
(Diets\)\()Tj
0.83 0.64 0.02 0 k
(Table)Tj
5.21 0 Td
(1)Tj
0 g
(\))Tj
1.0318 0 Td
(and)Tj
1.7348 0 Td
(fed)Tj
1.457 0 Td
(for)Tj
1.3833 0 Td
(16)Tj
1.1736 0 Td
(weeks)Tj
2.6078 0 Td
([)Tj
0.83 0.64 0.02 0 k
(24)Tj
0 g
(].)Tj
2.075 0 Td
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2.88 0 Td
(and)Tj
1.7291 0 Td
(perigona-)Tj
-33.4259 -1.2982 Td
(dal)Tj
1.4173 0 Td
(adipose)Tj
3.2484 0 Td
(tissue)Tj
2.4492 0 Td
(were)Tj
2.1089 0 Td
(collected)Tj
3.7304 0 Td
(from)Tj
2.194 0 Td
(fed)Tj
1.4513 0 Td
(and)Tj
1.7178 0 Td
(16)Tj
1.1622 0 Td
(h-fasted)Tj
3.4242 0 Td
(mice)Tj
2.143 0 Td
(following)Tj
3.9685 0 Td
(euthanasia)Tj
4.4617 0 Td
(by)Tj
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(decapi-)Tj
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(tation)Tj
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(to)Tj
1.0261 0 Td
(examine)Tj
3.6 0 Td
(the)Tj
1.4683 0 Td
(regulation)Tj
4.3087 0 Td
(of)Tj
1.0148 0 Td
(LPA)Tj
2.0012 0 Td
(receptor)Tj
3.5546 0 Td
(expression)Tj
4.4674 0 Td
(in)Tj
1.0375 0 Td
(response)Tj
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(to)Tj
1.0261 0 Td
(chronic)Tj
3.2882 0 Td
(obesity)Tj
-33.0971 -1.2983 Td
(and)Tj
1.7291 0 Td
(acute)Tj
2.3244 0 Td
(changes)Tj
3.4072 0 Td
(in)Tj
1.0318 0 Td
(nutritional)Tj
4.5354 0 Td
(status)Tj
2.5001 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
1.8199 0 Td
(1)Tj
0 g
(\).)Tj
1.2642 0 Td
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1.6271 0 Td
(subsequent)Tj
4.7055 0 Td
(qPCR)Tj
2.5681 0 Td
(studies,)Tj
3.2088 0 Td
(heart)Tj
2.2791 0 Td
(ventricles)Tj
-33.0007 -1.2983 Td
(and)Tj
1.7291 0 Td
(adipose)Tj
3.2598 0 Td
(tissue)Tj
2.4548 0 Td
(samples)Tj
3.3845 0 Td
(were)Tj
2.1203 0 Td
(snap-frozen)Tj
4.9833 0 Td
(in)Tj
1.0375 0 Td
(liquid)Tj
2.5625 0 Td
(nitrogen)Tj
3.651 0 Td
(and)Tj
1.7291 0 Td
(stored)Tj
2.7099 0 Td
(at)Tj
0.9524 0 Td
(-80C.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 274.337 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Primary)Tj
3.6283 0 Td
(mouse)Tj
3.1938 0 Td
(cardiomyocytes)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 257.3291 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Cardiomyocytes)Tj
6.7294 0 Td
(were)Tj
2.1259 0 Td
(isolated)Tj
3.2825 0 Td
(from)Tj
2.2054 0 Td
(chow)Tj
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(and)Tj
1.7292 0 Td
(HFHS-fed)Tj
4.3483 0 Td
(C57BL/6J)Tj
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(mice)Tj
2.1543 0 Td
(as)Tj
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(previously)Tj
-30.0413 -1.2982 Td
(described)Tj
4.0535 0 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
(].)Tj
2.0749 0 Td
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3.2542 0 Td
(hearts)Tj
2.6362 0 Td
(were)Tj
2.1259 0 Td
(immersed)Tj
4.235 0 Td
(in)Tj
1.0318 0 Td
(ice-cold)Tj
3.3902 0 Td
(mouse)Tj
2.8573 0 Td
(heart)Tj
2.2734 0 Td
(perfusion)Tj
4.0365 0 Td
(buffer)Tj
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(con-)Tj
-34.5937 -1.2983 Td
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(113)Tj
1.6441 0 Td
(mM)Tj
1.9332 0 Td
(NaCl,)Tj
2.5228 0 Td
(14.7)Tj
1.8766 0 Td
(mM)Tj
1.9275 0 Td
(KCl,)Tj
2.0296 0 Td
(0.6)Tj
1.4003 0 Td
(mM)Tj
1.9275 0 Td
(KH)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 397.5874 229.6629 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 401.1023 231.3637 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(PO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 414.1984 229.6629 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(4)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 417.7133 231.3637 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(,)Tj
0.4478 0 Td
(0.6)Tj
1.3947 0 Td
(mM)Tj
1.9332 0 Td
(Na)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 467.2062 229.6629 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 470.7212 231.3637 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(HPO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 491.4708 229.6629 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(4,)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 498.8976 231.3637 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(1.2)Tj
1.4003 0 Td
(mM)Tj
1.9275 0 Td
(MgSO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 558.0283 229.6629 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(4)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 561.5433 231.3637 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(,)Tj
0.4478 0 Td
(12)Tj
-36.6006 -1.3039 Td
(mM)Tj
1.9332 0 Td
(NaHCO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 252.7937 216.6803 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(3,)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 260.2204 218.3244 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
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