THE INTRODUCTION 123 I EXERCISE 4.1: INTRODUCTIONS 1. For each Introduction below, identify the steps in the story (known, un- ‘Inown, question, and also experimental approach, ifit is included). 2. Based on the summary of guidelines for Introductions, list the main strengths and weaknesses of each Introduction. Pay particular attention to the precise statement of the question and clear logical narrowing of the story of where the question came from. Also consider paragraph structure, sentence structure, and word choice. Also consider the tile. 3. Rewrite one of these Introductions, avoiding the weaknesses you named and heeping the strengths. Introduction 1 HEAT STORAGE IN RUNNING ANTELOPE: INDEPENDENCE OF BRAIN AND BODY TEMPERATURES 1 Athe existence of camels, oryxes, gazelles, and other ungulates in hot deserts has long fascinated physiologists. BUnlike rodents, these animals are too large to burrow and cannot escape the desert sun, CUnderstandably, most of the work on temperature regulation of ungulates has been concerned with heat loads from the environment (6, 8, 10, 12, 16, 17, 19, 20, 23). Pinternal heat loads, however, may pose thermal problems as great as or greater than the sun does. #Tremendous amounts of heat are produced when antelopes run at high speed. FGazelles and eland have been clocked at 70-80 km/h (43-50 mph). @Using the recently developed relationship between body size and energetic cost of locomotion (22), we can calculate that a 15-kg gazelle running at 70 km/h would be producing heat at 40 times its resting metabolic rate. HThese high bursts of speed are usually of short duration. “it seemed possible that antelopes might store rather than dissipate this heat. 2. Jrhis study set out to answer two simple questions: (1) Does heat stor- age play an important role? and (2) If heat storage is important, do these an- imals possess unusual physiological mechanisms for coping with high body temperatures? STRENGTHS WEAKNESSES124 THE TEXT OF THE BIOMEDICAL RESEARCH PAPER Introduction 2 ‘THE INHIBITORY EFFECT OF APOLIPOPROTEIN E4 ON NEURITE OUTGROWTH IS ASSOCIATED WITH MICROTUBULE DEPOLYMERIZATION 1 AApolipoprotein (apo) E is a 34-kDa protein component of lipoproteins that mediates their binding to the low density lipoprotein (LDL) receptor and to the LDL receptor-related protein (LRP) (1-4). BApolipoprotein E is a ma- Jor apolipoprotein in the nervous system, where it is thought to redistribute lipoprotein cholesterol among the neurons and their supporting cells and to maintain cholesterol homeostasis (5-7). CApart from this function, apo E in the peripheral nervous system functions in the redistribution of lipids during regeneration (8-10). 2 Dihere are three common isoforms of apo E (apoE2, apoE3, and apoE4) that are the products of three alleles (e2, e8, and e4) at a single gene locus on chromosome 19 (11). FApolipoprotein E3, the most common isoform, has cysteine and arginine at positions 112 and 158, respectively, whereas apoE2 has cysteine at both of these positions and apoE4 has arginine at both (1, 12). 3. FAccumulating evidence demonstrates that the apoE allele (e4) is specifically associated with sporadic and familial late-onset Alzheimer's dis- ease and is a major risk factor for the disease (13-16). GIn accord with these findings, apoE immunoreactivity is associated with both the amyloid plaques and the intracellular neurofibrillary tangles seen in postmortem examina- tions of brains from Alzheimer's disease patients (17, 18). HThe mechanism by which apoE4 might contribute to Alzheimer’s disease is unknown. THow- ever, our recent data demonstrating that apoE stunts the outgrowth of neu- rites from dorsal root ganglion (DRG) neurons suggest that apoE may have a direct effect on neuronal development or remodeling (19, 20). In an exten- sion of these previous studies, we have now examined the effects of the apoE isoforms on neurite outgrowth and on the cytoskeleton of Neuro-2a cells, a murine neuroblastoma cell line. KApolipoprotein E4 inhibits neurite out- growth from these cells, and this isoform-specific effect is associated with de- polymerization of microtubules. STRENGTHS WEAKNESSESTHE INTRODUCTION 125 Introduction 3 ‘THE SEQUENCE OF EXPOSURE TO THE STIMULI DETERMINES THE EFFECT OF ALKALOSIS ON HYPOXIA-INDUCED PULMONARY VASOCONSTRICTION IN LUNGS FROM NEWBORN RABBITS 1 AAlveolar hypoxia causes pulmonary vasoconstriction. BTo determine whe- ther alkalosis or acidosis can increase or reduce hypoxia-induced pulmonary vasoconstriction, numerous investigators have studied the effects of alkalosis and acidosis on constriction of the pulmonary circulation in response to hypoxia (1-14), COnly a few of these investigators have studied the effect of alkalosis on hypoxia-induced pulmonary vasoconstriction in the lungs of newborn ani- ‘mals (10, 18, 14), DThe results of these studies have been variable. FAlkalosis has been shown either to reduce or to have no effect on constriction of the neonatal pulmonary circulation in response to alveolar hypoxia. 2 FUnderstanding the effect of alkalosis on the neonatal pulmonary cireula- tion and on the response of the pulmonary circulation to hypoxia is important because alkalosis, produced primarily by mechanical hyperventilation, is widely used in the treatment of newborns who have the syndrome of persistent pul- monary hypertension (15, 16). @Mechanical hyperventilation is often clinically effective in the treatment of these infants, but it is not clear whether the im- provements are due to the alkalosis resulting from the therapy. If alkalosis is responsible for the clinical improvement in these infants, it is possible that some of the deleterious effects of mechanical hyperventilation could be avoided by using alternative means of inducing alkalosis. JA clearer understanding of the effect of alkalosis on the constriction of the neonatal pulmonary circulation in response to hypoxia would aid in the management of these patients. 3 IThe purpose of this study was to determine whether or not alkalosis re- duces constriction of the neonatal pulmonary circulation in response to hy- poxia by answering the following specific questions: 1) does alkalosis reduce pulmonary vascular resistance after it has increased in response to hypoxia, 2) does alkalosis reduce the ability of the pulmonary circulation to constrict in response to subsequent hypoxia, 3) does alkalosis introduced simultane- ously with hypoxia reduce constriction of the pulmonary circulation, and 4) do both respiratory and metabolic alkalosis have the same effect on the pul- monary circulation and its response to hypoxia. K'To answer these questions, SF126 THE TEXT OF THE BIOMEDICAL RESEARCH PAPER we exposed isolated perfused lungs of newborn rabbits to alkalosis and alveo- lar hypoxia. LFor each pair of lungs we used one of the following three se- quences of exposure to the stimuli: 1) alveolar hypoxia followed by metabolic or respiratory alkalosis, 2) metabolic or respiratory alkalosis followed by alve- olar hypoxia, or 3) simultaneous alveolar hypoxia with respiratory alkalosis, ‘MWe found that both metabolic and respiratory alkalosis reduced pulmonary vascular resistance that was elevated in response to hypoxia; neither meta- bolic nor respiratory alkalosis reduced constriction of the pulmonary vascula- ture in response to subsequent hypoxia; and simultaneous respiratory alkalo- sis and hypoxia significantly reduced pulmonary vascular constriction. NWe conclude that the sequence of exposure to the stimuli determines the effect of both respiratory and metabolic alkalosis on hypoxia-induced pulmonary vaso- constriction in isolated, perfused lungs of newborn rabbits, ‘STRENGTHS WEAKNESSES