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Biomedical subjects

M A Wilson

Publications and source records attributed to M A Wilson.

At least 127 records · Page 7Linked to original sources
PubMed1996

Platelet-activating factor mediates pulmonary macromolecular leak following intestinal ischemia-reperfusion.

Platelet-activating factor (PAF) causes hypotension, cardiac dysfunction, increased vascular permeability, intestinal necrosis, and pulmonary microvascular injury when administered experimentally. Receptor antagonism attenuates or abolishes many of these effects in animal models of bacteremia, endotoxemia, and intestinal ischemia/reperfusion (I/R). The purpose of this study was to further examine the role of PAF in intestinal I/R-induced pulmonary injury using the PAF receptor antagonist WEB 2086. Sprague-Dawley rats were anesthetized and cannulated for measurement of mean arterial pressure, heart rate, and cardiac output. Laparotomy and thoracotomy were performed and the superior mesenteric artery was occluded for 45 min and reperfused for 120 min. Sham animals were treated similarly but without I/R. In the treatment groups, iv WEB 2086 (20 mg/kg/l cc NS) was administered as a bolus 15 min prior to reperfusion. Hemodynamic and videomicroscopic data were obtained before and during ischemia, and after reperfusion at 30-min intervals. Alveolar leak index was calculated offline via computer analysis of videomicroscopic images. Intestinal I/R caused pulmonary macromolecular leakage and hemodynamic instability. Treatment with WEB 2086 attenuated the pulmonary leak during the entire reperfusion period but improved cardiac output only during the first 30 min of reperfusion and had no effect on other hemodynamic variables. These data suggest that PAF is an important, but not the exclusive, mediator of pulmonary injury after intestinal I/R. PAF appears to play a minor role in the hemodynamic derangements observed after rat intestinal I/R.

Animals↗
PubMed1996

Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences.

O'Keefe and Recce [1993] Hippocampus 3:317-330 described an interaction between the hippocampal theta rhythm and the spatial firing of pyramidal cells in the CA1 region of the rat hippocampus: they found that a cell's spike activity advances to earlier phases of the theta cycle as the rat passes through the cell's place field. The present study makes use of large-scale parallel recordings to clarify and extend this finding in several ways: 1) Most CA1 pyramidal cells show maximal activity at the same phase of the theta cycle. Although individual units exhibit deeper modulation, the depth of modulation of CA1 population activity is about 50%. The peak firing of inhibitory interneurons in CA1 occurs about 60 degrees in advance of the peak firing of pyramidal cells, but different interneurons vary widely in their peak phases. 2) The first spikes, as the rat enters a pyramidal cell's place field, come 90 degrees-120 degrees after the phase of maximal pyramidal cell population activity, near the phase where inhibition is least. 3) The phase advance is typically an accelerating, rather than linear, function of position within the place field. 4) These phenomena occur both on linear tracks and in two-dimensional environments where locomotion is not constrained to specific paths. 5) In two-dimensional environments, place-related firing is more spatially specific during the early part of the theta cycle than during the late part. This is also true, to a lesser extent, on a linear track. Thus, spatial selectivity waxes and wanes over the theta cycle. 6) Granule cells of the fascia dentata are also modulated by theta. The depth of modulation for the granule cell population approaches 100%, and the peak activity of the granule cell population comes about 90 degrees earlier in the theta cycle than the peak firing of CA1 pyramidal cells. 7) Granule cells, like pyramidal cells, show robust phase precession. 8) Cross-correlation analysis shows that portions of the temporal sequence of CA1 pyramidal cell place fields are replicated repeatedly within individual theta cycles, in highly compressed form. The compression ratio can be as much as 10:1. These findings indicate that phase precession is a very robust effect, distributed across the entire hippocampal population, and that it is likely to be inherited from the fascia dentata or an earlier stage in the hippocampal circuit, rather than generated intrinsically within CA1. It is hypothesized that the compression of temporal sequences of place fields within individual theta cycles permits the use of long-term potentiation for learning of sequential structure, thereby giving a temporal dimension to hippocampal memory traces.

Animals↗
PubMed1996

Vasomotor response to pentoxifylline mediates improved renal blood flow to bacteremia.

Bacteremia leads to rapid intrarenal vasoconstriction, mediated by endogenous vasoconstrictors such as TXA2 and endothelin. These changes occur before the onset of neutrophil adherence, platelet aggregation, or increases in proinflammatory cytokines. Pentoxifylline (PTX) increases red cell deformability, reduces neutrophil adhesion, abrogates rises in TNFalpha, and lessens the deleterious effects of other cytokines during prolonged sepsis. PTX also improves renal function in models of established sepsis, but the specific mechanisms of this effect are unclear. Because PTX is a relatively selective visceral vasodilator we sought to determine whether PTX improves renal microvascular hypoperfusion during bacteremia and whether the mechanism involves altered vascular reactivity. Rat hydronephrotic kidneys were studied by videomicroscopy. Interlobular (ILA) arteriolar diameter and flow, afferent (AFF) and efferent (EFF) arteriolar diameters, and cardiac output (CO) were measured at 15-min intervals for 120 min. PTX was infused alone or prior to a bolus injection of live Escherichia coli. The responses were compared to controls infused with equivalent volumes of normal saline alone. PTX led to improved renal blood flow and to pre- and postglomerular vasodilatation. This improvement remained significant compared to bacteremic animals throughout the period of observation. We conclude that PTX improves renal blood flow during bacteremia due to pre- and postglomerular vasodilation. These responses may be a consequence of increased intracellular cAMP and release of vasodilator prostanoids.

Animals↗
PubMed1996

Heparan preserves intestinal perfusion after hemorrhage and resuscitation.

BACKGROUND: Multiple system organ failure (MOF) remains a major source of morbidity and mortality in trauma patients. Despite restoration of central hemodynamics, intestinal hypoperfusion can persist. Mucosal ischemia and barrier breakdown are factors in the genesis of MOF. Heparan sulfate is a gycosaminoglycan similar to heparin, but with minimal anticoagulant properties. As an adjunct to resuscitation, it improves immunologic function and restores mucosal oxygenation and function. We hypothesized that resuscitation with heparan following hemorrhage wound prevents intestinal hypoperfusion. MATERIALS AND METHODS: In vivo videomicroscopy was used to study small intestine microcirculation in rats. Animals were hemorrhaged to 50% of baseline mean arterial pressure (MAP) and maintained there. Resuscitation was initiated when the return of 10% shed blood was required to keep MAP at 50%. Animals received either heparan (7 mg/kg/1 ml saline) or saline (1 ml) followed by the remaining shed blood and an equal volume of saline. MAP, cardiac output (CO), A1 arteriole diameters, and flow were determined. RESULTS: Resuscitation of the saline control group resulted in normal MAP with elevation of CO to 25-40% above baseline. The heparan group had return of MAP but only a moderate increase in CO (7-15%). Saline resuscitation led to progressive deterioration in A1 diameters and flow. The addition of heparan prevented delayed A1 constriction and significantly improved perfusion. CONCLUSIONS: Heparan prior to resuscitation improved intestinal perfusion, despite a relative reduction in CO. Improvement in nutrient blood flow may protect the mucosal barrier, reducing the incidence of MOF, and suggests that heparan may be useful in resuscitation of trauma patients.

Animals↗
PubMed1996

Early postnatal alcohol exposure in rats: maternal behavior and estradiol levels.

Long Evans male and female rats were exposed to alcohol or control conditions during the early postnatal period, and their maternal behavior was assessed between 25 and 29 days of age. Maternal behavior was induced by exposing experimental animals to pups, and behaviors included retrieval of pups and proximity to pups. After 5 days of continuous exposure to pups, experimental animals were decapitated, and trunk blood was measured for levels of estradiol and progesterone. Alcohol-exposed animals showed a deficit in maternal behavior as measured by a longer latency to retrieve pups than rats that were not treated with alcohol. In addition, alcohol-exposed animals had lower levels of circulating estradiol than controls. These effects may also be explained by undernutrition as a result of artificial rearing. No difference in progesterone levels was found. As estradiol is important for the onset of maternal behavior in adult rats, it may be that the alcohol-induced decrease in estradiol levels underlies the deficit in maternal behavior exhibited by alcohol-exposed rats.

Animals↗
PubMed1996

Increased open field locomotion and decreased striatal GABAA binding after activity wheel running.

Open-field behavior has been used to model reductions in anxiety-related behaviors in the rat after chronic physical activity. Plausible mechanisms for the increased open field locomotion observed after physical activity have not been studied. Open field locomotion is decreased by gamma-aminobutyric acid (GABA) and its agonists, and increased by GABA antagonists, in the ventral striatum. Hence, we tested the hypothesis that increased open field locomotion following chronic physical activity would be accompanied by a decrease in the number of GABAA receptors in the corpus striatum. Young (approximately 55 days) male Sprague-Dawley rats (N = 24) were randomly assigned to three conditions: 24-h access to an activity wheel (AW), running for 1 h without shock 6 days/week on a motorized treadmill (TM), or sedentary control (C). Open field locomotion (total and center squares traversed), defecation, and urination were assessed on each of 3 consecutive days prior to and again after 8 weeks of physical activity. Open field locomotion (total and center squares) increased after activity wheel running, decreased after treadmill training, and did not change for control animals. GABAA receptor density indicated by [3H] bicuculline binding (fmol/mg) was lower for activity wheel animals compared with treadmill animals and controls. GABA concentration (mumol/g) was not different between activity wheel and treadmill groups but was higher for both groups contrasted with controls. Our findings of decreased GABAA density in the corpus striatum concomitant with an increase in open field locomotion are consistent with an anxiolytic effect of chronic activity wheel running.

Animals↗
PubMed1996

The application of ESEM in dental materials research.

OBJECTIVES: To describe the use of environmental scanning electron microscopy (ESEM) to investigate acid etching of enamel and to comment on future applications of ESEM in dental materials research. METHODS: The acid etching of axially fractured specimens of human enamel by a 35% (ortho) phosphoric acid etchant was observed using ESEM. RESULTS: Most of the etching action, as evidence by gaseous bubbling in the etchant film, was observed to occur within 10 s of applying the etchant. High magnification examination of the etched areas revealed distinct etching patterns. CONCLUSION: ESEM may play an important role in developing the understanding and existing knowledge pertaining to dynamic chemical and physical interactions between components of restorative systems and tooth tissue substrates.

Acid Etching, Dental↗
PubMed1996

Free radical scavenging by lazaroids improves renal blood flow during sepsis.

BACKGROUND: Acute kidney failure in surgical patients is often related to severe infection. Renal vasoconstriction is a major factor in the genesis of kidney failure. Reactive oxygen species (ROS) are known to mediate kidney injury after ischemia-reperfusion and are increased during sepsis. The role of ROS as mediators of intrarenal vasoconstriction and renal dysfunction during sepsis is unclear. Lazaroids such as U74389G are radical quenching antioxidants that inhibit ROS-induced lipid peroxidation. We sought to determine whether radical scavenging affected the renal microvascular response to a septic challenge. METHODS: In vivo videomicroscopy was used to study the rat hydronephrotic kidney. Interlobular artery (ILA) diameter and flow, afferent and efferent arteriolar diameters, and cardiac output were measured. U74389G or vehicle was infused before a bolus injection of live Escherichia coli or normal saline solution. RESULTS: U74389G alone had no effect on the renal vessels or hemodynamics. E. coli caused preglomerular vasoconstriction (ILA, -32%; afferent, -30% of baseline) and hypoperfusion (-66%) despite increased cardiac output (+54%). U74389G significantly attenuated both the constriction (ILA, -16%; afferent, -9%) and hypoperfusion (-38%) but not increased cardiac output (+41%). CONCLUSIONS: E. coli bacteremia led to preglomerular vasoconstriction and hypoperfusion. Inhibition of lipid peroxidation with the radical scavenger U74389G reduced this effect without altering central hemodynamic responses. Free radicals have a deleterious effect on the renal microcirculation during bacteremia, and these data suggest that antioxidants may be of value in preventing sepsis-associated kidney failure.

Animals↗
PubMed1996

Operative strategies for management of abdominal aortic gunshot wounds.

BACKGROUND: Although management of penetrating abdominal trauma has greatly improved, abdominal aortic gunshot wounds (AAGSWs) remain a highly lethal injury. Our experience with AAGSWs was reviewed to define operative strategies that may improve survival. METHODS: Forty-one patients with AAGSWs were treated between 1976 and 1996. Preliminary thoractomy was performed in seven patients. Thirty-nine patients had at least one major associated injury (average, 3.2). RESULTS: Twenty-one patients died. Six of seven patients who underwent preliminary thoracotomy died; all developed coagulopathy, which appeared to contribute to death. Four patients had missed vascular lesions, two of which contributed to their death. Associated injuries are currently managed by "damage control" strategy, in which some injuries are left untreated to focus on hemorrhage control. CONCLUSIONS: We have identified seven operative principles and procedures that we believe may improve survival: (1) thorough knowledge of supraceliac exposure; (2) rapid aortic control at the hiatus rather than by a preliminary thoracotomy; (3) use damage control or abbreviated laparotomy; (4) use packing and mesh closure when coagulopathy and hypothermia are present; (5) primary concern should be cessation of hemorrhage rather than the maintenance of flow; (6) delayed reconstruction using extraanatomic bypass can restore flow; and (7) use angiography to detect missed vascular lesions or problems with vascular repair.

Adult↗
PubMed1996

Measurement of bone mineral density by dual-energy x-ray absorptiometry in patients with the Wisconsin hip, an uncemented femoral stem.

Although qualitative evidence of femoral bone remodeling, secondary to total hip arthroplasty (THA), is apparent on radiographs, quantification of change in bone mass from radiographs is limited. Dual-energy x-ray absorptiometry overcomes many of the limitations and yields accurate and precise bone mineral density (BMD) data. In this study, regional changes in femoral BMD were examined in 89 THA patients with a 2-year follow-up period. Thirty-two patients were evaluated initially before surgery and followed through the first 2 postoperative years. A second group was comprised of 57 patients whose surgery had been performed 1 to 6 years prior to entry into the study; they were also followed for 2 years hence. Thus, both immediate and later bone responses were evaluated prospectively. Maximal bone remodeling was seen in the first 6 months after THA and with a near plateau by the end of the first year. A slow yearly decline in BMD appeared to occur as long as 8 years after THA, thus demonstrating the long-term effects of the introduction of a femoral stem. Variance in preoperative BMD was explained by disease only; no other factors (age, weight, sex) showed significant associations, and body weight was the only variable that affected rate of remodeling after THA (not age, weight, sex, prosthesis size, nor disease). All patients were healthy, relatively young individuals who were good candidates for uncemented implantation, and none showed evidence of clinical complications or surgical failure. It is therefore suggested that the patterns and results reported here be viewed as normative data, that is, the typical skeletal adaptation to THA. In future application, observation of disparate BMD results as compared with these "normal" data may be predictive of abnormal response to surgery and potential for later problems.

Absorptiometry, Photon↗
PubMed1996

Delivery of human fibroblast growth factor-1 gene to brain by modified rat brain endothelial cells.

Fibroblast growth factor (FGF) is an endothelial cell mitogen and serves as a mitogen and/or differentiating factor that can be neuroprotective for other cell types within the CNS. We established brain microvascular endothelial cell lines that secrete FGF-1 with the ultimate goal of examining their usefulness as a cellular platform for FGF gene delivery to brain. A chimeric gene consisting of the secretory sequence of FGF-4 linked at the 5' end of human FGF-1 (sp-hst/KS3:FGF-1) was transfected into rat microvascular endothelial cells previously altered to express the lacZ reporter gene (RBEZ), and numerous clones were found to secrete FGF-1 (RBEZ-FGF). Immunoblotting of conditioned medium demonstrated an 18-kDa protein corresponding to FGF-1. Conditioned medium from RBEZ-FGF cells enhanced [3H]thymidine incorporation in BALB/c3T3 fibroblasts by up to sevenfold when compared with conditioned medium of control cell lines, corresponding to as much as 110 ng of active FGF-1/mg of cell protein/24 h. RBEZ-FGF cell lines remained contact-inhibited and proliferated independent of exogenous endothelial mitogens, in contrast to control lines that are mitogen-dependent. Incubation of PC12 cells with RBEZ-FGF cells or their conditioned medium induced neurite outgrowth by PC12 cells. RBEZ-FGF cells survived following implantation to neonatal and adult rat caudate-putamen for at least 21 days based on 5-bromo-4-chloro-3-indolyl beta-D-galactopyranoside (X-gal) histochemistry, and FGF-1 gene expression by these cells in vivo was demonstrated by in situ hybridization and reverse transcriptase-PCR. These findings suggest that endothelial cells may be useful for FGF gene delivery to the CNS.

Animals↗
PubMed1996

Predicting the need to pack early for severe intra-abdominal hemorrhage.

OBJECTIVE: To determine if the decision to pack for hemorrhage could be refined. MATERIALS AND METHODS: Seventy consecutive trauma patients for whom packing was used to control hemorrhage were studied. The patients had liver injuries, abdominal vascular injuries, and bleeding retroperitoneal hematomas. Preoperative variables were analyzed and survivors compared with nonsurvivors. RESULTS: Packing controlled hemorrhage in 37 (53%) patients. Significant differences (p < 0.05) between survivors and nonsurvivors were Injury Severity Score (29 vs. 38), initial pH (7.3 vs. 7.1), platelet count (229,000 vs. 179,000/mm3), prothrombin time (14 vs. 22 seconds), partial thromboplastin time (42 vs. 69 seconds), and duration of hypotension (50 vs. 90 minutes). Nonsurvivors received 20 units of packed red blood cells before packing compared to 13 units for survivors. CONCLUSION: Patients who suffer severe injury, hypothermia, refractory hypotension, coagulopathy, and acidosis need early packing if they are to survive. Failure to control hemorrhage is related to severity of injury and delay in the use of pack tamponade. A specific protocol that mandates packing when parameters reach a critical limit should be considered.

Abdominal Injuries↗
PubMed1996

Fluid resuscitation attenuates early cytokine mRNA expression after peritonitis.

OBJECTIVE: To study the hypothesis that fluid resuscitation alters cytokine gene expression after experimental murine peritonitis. MATERIALS AND METHODS: Mice underwent cecal ligation and puncture (CLP) to induce peritonitis and were randomized to receive variable amounts of normal saline (0, 0.25, 1.0 ml. subcutaneously) and serum (0 or 0.1 mL) after operation. Hepatic and small intestinal (ileal) tissue were harvested at 3 or 6 hours after CLP, and total tissue RNA was extracted. Reverse transcriptase polymerase chain reaction was used to provide relative quantitation of tumor necrosis factor-alpha and interleukin (IL)-1 beta messenger RNA (mRNA) compared with beta-actin. RESULTS: CLP without resuscitation resulted in significant increases in hepatic tumor necrosis factor-alpha mRNA (1190% at 6 hours compared with normal animals), and IL-1 beta mRNA (1475%), and intestinal IL-1 beta mRNA (1243%). Volume administration attenuated cytokine expression at both 3 and 6 hours, and saline seemed to have more potent effects than serum. The volume of resuscitation correlated with survival at 18 hours. Survival in the saline (1 mL) + serum group was 90% at 18 hours compared with 20 to 40% in the groups with little or no resuscitation. Overall, there were no survivors at 30 hours. CONCLUSIONS: Fluid resuscitation (amount, composition, timing) should be an important consideration in the utilization of experimental infection models. Furthermore, optimization of the patient's intravascular volume status during sepsis may have important effects on immune responses, in addition to improving hemodynamic variables.

Animals↗
PubMed1996

GABA physiology: modulation by benzodiazepines and hormones.

This review compares the ability of acute and chronic benzodiazepine treatments (BZs), gonadal hormone treatments, and neurosteroids to modify gamma-aminobutyric acid (GABA) physiologic responses in animals. Both BZ ligands and certain "neurosteroid" derivatives of steroid hormones can modulate GABA responses through direct interactions with the GABA receptor complex. Fluctuations in gonadal steroids can be anticonvulsant or proconvulsant, anxiolytic or anesthetic, suggesting a pharmacologic profile comparable to that of the BZs. A comparison of neuronal physiological responses in spinal cord, hippocampus, amygdala, hypothalamus-preoptic area, cerebellum, dorsal raphe, locus coeruleus, and cortex indicates that both acute and chronic BZ treatments produce region-specific effects on in vivo GABAergic responses. This appears to be based on regional variability in intrinsic sensitivity to GABA and/or BZ ligands, the level of ongoing GABA neurotransmission in a region, and the indirect influences of BZs on afferent inputs to an area. Regionally specific adaptations to chronic BZ treatments that lead to the development of tolerance include the following: intrinsic subsensitivity to GABA, reduced activity in GABAergic circuits (e.g., reduced recurrent inhibition in hippocampus), attenuated responses to BZs without alterations in GABA sensitivity, modulation of the intrinsic properties of neurons, and alterations in the activity of non-GABAergic afferent inputs. The in vivo evidence that neurosteroid derivatives modify physiological responses to GABA is also beginning to emerge. Progesterone, through conversion to its neurosteroid metabolite 3 alpha-OH DHP, potentiates GABA responses of cerebellar Purkinje cells. This neurosteroid also enhances GABA responses in hippocampal slices, including recurrent inhibition, in a BZ-like manner. Despite the evidence that fluctuations in estrogen levels can modulate several aspects of GABA neurotransmission, neither in vivo estrogen treatments nor in vitro administration of estrogen to brain slices clearly modifies physiological GABA responses. Although estrogens alter excitability in several areas, these changes are associated with estrogenic effects on responses to excitatory neurotransmitters or inputs. Relatively few studies have examined the in vivo influences of androgenic steroids on GABA responses.

Animals↗
PubMed1996

Preoperative saline loading improves outcome after elective, noncardiac surgical procedures.

Patients with multiple system disease undergoing elective noncardiac surgical procedures are at variable risk for developing postoperative complications and death. To determine whether preoperative expansion of plasma volume would improve outcome, 306 patients were admitted to the Surgical Intensive Care Unit of the Veterans Administration Center for Swan-Ganz catheter placement and measurement of hemodynamic responses to a 2 L infusion of normal saline over 2 hours. Intraoperative stability and postoperative outcome were assessed by chart review and compared with similar operative groups of patients who did not receive saline infusion. Eighty-eight per cent of the patients had a positive expansion of blood volume with saline infusion. In patients undergoing aortic reconstructive procedures, there was a reduction in the incidence of postoperative complications (52% to 28%) primarily attributed to a reduction in pulmonary complications. In all patients there was an improvement in intraoperative cardiovascular stability (57% saline vs 38% control), a reduction in the need for pharmacologic support of blood pressure (19% saline vs 30% control), and reduction in the amount of intraoperative fluid administration (hydration index: 5.12 saline vs 8.61 control). We therefore conclude that preoperative saline loading is associated with improved outcome in high risk elderly patients undergoing elective, noncardiac surgical procedures.

Adult↗
PubMed1996

Effects of benzodiazepine agonist exposure on corticotropin-releasing factor content and hormonal stress responses: divergent responses in male and ovariectomized female rats.

Benzodiazepine agonists affect endocrine responses of the hypothalamic-pituitary-adrenal axis and can antagonize many of the actions of corticotropin-releasing factor (CRF). Gender and gonad-related factors can influence both the development of tolerance to the benzodiazepines in rats and the concomitant neural adaptations associated with chronic benzodiazepine agonist exposure. This study compared changes in CRF content, corticosterone release and ACTH levels after diazepam exposure in ovariectomized female (OVX) and male rats. After treatment with diazepam for 3 days (acute) or 3 weeks (chronic), content of CRF immunoreactivity in eight brain areas and serum corticosterone were determined by radioimmunoassay in handling-habituated rats. The effects of acute and chronic benzodiazepine exposure on swim stress-induced corticosterone and ACTH release were also examined. Chronic diazepam exposure reduced stress-induced corticosterone and ACTH release in OVX, but not male, rats. Acute diazepam exposure similarly attenuated stress-induced corticosterone release in OVX rats, but did not affect ACTH release. OVX control groups had greater levels of CRF than males in several brain regions. Gender-specific alterations in CRF content after chronic diazepam exposure were observed in amygdala, locus ceruleus and median eminence. Chronic benzodiazepine agonist exposure increased CRF levels in the amygdala of OVX rats, but not males. Both chronic and acute diazepam exposure increased CRF content in the locus ceruleus of male, but not OVX, rats. These results indicate that the effects of benzodiazepine exposure on neural CRF systems are region specific and influenced by gender-related factors.

Adrenocorticotropic Hormone↗
PubMed1996

Molecular modeling of protocellular functions.

The mechanisms of three protocellular functions have been studied using molecular modeling techniques. These functions are (1) the transport of ions across membranes, (2) the formation of photoactivated proton gradient that could drive chemical synthesis in the protocell, and (3) the organization of small peptides necessary for catalytic activity. In all these processes, membranes play an essential role. The transfer of ions across the barrier formed by protocellular walls is facilitated by the formation of deep, thinning defects in the membrane. Membranes also form a barrier to charged species that allows for retaining proton gradients. These gradients can be generated by a simple transmembrane proton pump consisting of a proton source and two acceptors. The directionality of the pump is ensured by a "gate-keeping" mechanism involving a water molecule, conformational change of the primary acceptor or tautomerization of a histidine. The pump can be formed by two transmembrane helices but not one helix. They provide surfaces at which organic molecules concentrate and small peptides can organize into ordered, amphiphilic structures. In general, valuable information about the origins and evolution of protocells can be obtained from the knowledge of physical and chemical principles that govern functioning of contemporary cells.

Amino Acid Sequence↗