Epigenomic Convergence of Neural-Immune Risk Factors in Neurodevelopmental Disorder Cortex.

Neurodevelopmental disorders (NDDs) affect 7-14% of all children in developed countries and are one of the leading causes of lifelong disability. Epigenetic modifications are poised at the interface between genes and environment and are predicted to reveal insight into NDD etiology. Whole-genome bisulfite sequencing was used to examine DNA cytosine methylation in 49 human cortex samples from 3 different NDDs (autism spectrum disorder, Rett syndrome, and Dup15q syndrome) and matched controls. Integration of methylation changes across NDDs with relevant genomic and genetic datasets revealed differentially methylated regions (DMRs) unique to each type of NDD but with shared regulatory functions in neurons and microglia. NDD DMRs were enriched within promoter regions and for transcription factor binding sites with identified methylation sensitivity. DMRs from all 3 disorders were enriched for ontologies related to nervous system development and genes with disrupted expression in brain from neurodevelopmental or neuropsychiatric disorders. Genes associated with NDD DMRs showed expression patterns indicating an important role for altered microglial function during brain development. These findings demonstrate an NDD epigenomic signature in human cortex that will aid in defining therapeutic targets and early biomarkers at the interface of genetic and environmental NDD risk factors.

Central arterial stiffness and diastolic dysfunction are associated with insulin resistance and abdominal obesity in young women but polycystic ovary syndrome does not confer additional risk.

STUDY QUESTION: Are arterial stiffness, carotid intima-media thickness and diastolic dysfunction increased in young women with polycystic ovary syndrome (PCOS) independently of the effects of obesity? SUMMARY ANSWER: Insulin resistance and central obesity are associated with subclinical cardiovascular dysfunction in young women, but a diagnosis of PCOS does not appear to confer additional risk at this age. WHAT IS KNOWN ALREADY: Some studies have shown that young women with PCOS may have increased measures of cardiovascular risk, including arterial stiffness, carotid intima-media thickness and myocardial dysfunction. However, it is difficult to establish how much of this risk is due to PCOS per se and how much is due to obesity and insulin resistance, which are common in PCOS and themselves associated with greater vascular risk. STUDY DESIGN, SIZE, DURATION: This cross-sectional study comprised 84 women with PCOS and 95 healthy volunteers, aged 16-45 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted in a university hospital. Subjects underwent a comprehensive assessment of body composition (including computed tomography (CT) assessment of visceral fat; VF), measurements of arterial stiffness (aortic pulse wave velocity; aPWV), common carotid intima-media thickness (ccIMT), diastolic function (longitudinal tissue velocity; e':a') and endocrinological measures. A sample size of 80 in each group gave 80% power for detecting a difference of 0.45 m/s in aPWV or a difference of 0.25 in e':a'. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment for age and body mass index (BMI), PCOS subjects had a greater insulin response (insulin area under the curve-IAUC) following glucose challenge (adjusted difference [AD] 35 900 pmol min/l, P < 0.001) and higher testosterone (AD 0.57 nmol/l, P < 0.001) and high molecular weight adiponectin than controls (AD 3.01 µg/ml, P = 0.02), but no significant differences in aPWV (AD -0.13 m/s, P = 0.33), ccIMT (AD -0.01 mm, P = 0.13), or e':a' (AD -0.01, P = 0.86) were observed. After adjustment for age, height and central pulse pressure, e':a' and aPWV were associated with logVF and IAUC. ccIMT was not related to logVF. The relationships between e':a' or aPWV and insulin resistance were only partly attenuated by adjusting for logVF. There was no significant relationship between aPWV or e':a' and either testosterone or adiponectin. LIMITATIONS, REASONS FOR CAUTION: The study recruited young women meeting the Rotterdam criteria for PCOS diagnosis; hence our findings may not be generalizable to older patients or those meeting other definitions of the syndrome. Biochemical hyperandrogenism was based solely on measurement of total testosterone. Cases and controls were not matched in advance for age and BMI, although the influence of these variables on the cardiovascular outcome measures was adjusted for. WIDER IMPLICATIONS OF THE FINDINGS: This study shows that central arterial stiffness and diastolic dysfunction are not increased in young women with PCOS, whereas they are associated with both insulin resistance and central obesity. Obesity thus represents the greatest modifiable risk factor for cardiovascular disease in young women with PCOS and lifestyle measures which target weight reduction are critical. STUDY FUNDING/COMPETING INTERESTS: This study received no specific grant support from any funding body. The authors have no conflicts of interest to declare.

Cyclin-like accumulation and loss of the putative kinetochore motor CENP-E results from coupling continuous synthesis with specific degradation at the end of mitosis.

CENP-E is a kinesin-like protein that binds to kinetochores through the early stages of mitosis, but after initiation of anaphase, it relocalizes to the overlapping microtubules in the midzone, ultimately concentration in the developing midbody. By immunoblotting of cells separated at various positions in the cell cycle using centrifugal elutriation, we show that CENP-E levels increase progressively across the cycle peaking at approximately 22,000 molecules/cell early in mitosis, followed by an abrupt (> 10 fold) loss at the end of mitosis. Pulse-labeling with [35S]methionine reveals that beyond a twofold increase in synthesis between G1 and G2, interphase accumulation results primarily from stabilization of CENP-E during S and G2. Despite localizing in the midbody during normal cell division, CENP-E loss at the end of mitosis is independent of cytokinesis, since complete blockage of division with cytochalasin has no affect on CENP-E loss at the M/G1 transition. Thus, like mitotic cyclins, CENP-E accumulation peaks before cell division, and it is specifically degraded at the end of mitosis. However, CENP-E degradation kinetically follows proteolysis of cyclin B in anaphase. Combined with cyclin A destruction before the end of metaphase, degradation of as yet unidentified components at the metaphase/anaphase transition, and cyclin B degradation at or after the anaphase transition, CENP-E destruction defines a fourth point in a mitotic cascade of timed proteolysis.

ArrayExpress--a public database of microarray experiments and gene expression profiles.

UNLABELLED: ArrayExpress is a public database for high throughput functional genomics data. ArrayExpress consists of two parts--the ArrayExpress Repository, which is a MIAME supportive public archive of microarray data, and the ArrayExpress Data Warehouse, which is a database of gene expression profiles selected from the repository and consistently re-annotated. Archived experiments can be queried by experiment attributes, such as keywords, species, array platform, authors, journals or accession numbers. Gene expression profiles can be queried by gene names and properties, such as Gene Ontology terms and gene expression profiles can be visualized. ArrayExpress is a rapidly growing database, currently it contains data from >50,000 hybridizations and >1,500,000 individual expression profiles. ArrayExpress supports community standards, including MIAME, MAGE-ML and more recently the proposal for a spreadsheet based data exchange format: MAGE-TAB. AVAILABILITY: www.ebi.ac.uk/arrayexpress.

L-histidine augments the response to 1-deamino-8-D-arginine vasopressin in Brattleboro homozygous (di/di) rats.

Studies in vitro have shown that L-histidine increases the hydroosmotic response to vasopressin. We examined whether this phenomenon occurs also in vivo. Homozygous Brattleboro rats (di/di) were fed a regular diet (0.5% histidine) or a diet enriched with histidine and received 1 ng of 1-deamino-8-D-arginine vasopressin (dDAVP) daily. Addition of histidine (1% by weight) increased post-dDAVP urine osmolality to a level higher than that of control (502 +/- 62 vs. 316 +/- 36 mosmol/kg, P less than 0.05). Similar results were seen with 3.0% and 5.5% dietary histidine. There were significant increases in free-water reabsorption and in the ratio of free-water reabsorption to osmolar clearance, but no difference in osmolal clearance. No significant effect was found with supplemental histidine of 0.5% or less. The cause for these findings appears not to be the metabolism of histidine, since the nonmetabolizable D-histidine had a significant, albeit smaller, effect, and the isonitrogenous addition of albumin, alanine, arginine, or glutamine was ineffective. In part, histidine may operate by increasing cAMP since the renal cAMP content in response to vasopressin is increased in histidine-fed rats (13.1 +/- 0.9 vs. 9.8 +/- 0.8 nmol/g dry weight, P less than 0.01). The role of prostaglandins appears less clear. Histidine greatly decreased urinary PGE2 during baseline (1.5 +/- 0.3 vs. 7.0 +/- 2.3 micrograms/mg creatinine, P less than 0.001), but it profoundly augmented urinary prostaglandin excretion after dDAVP stimulation (40.0 +/- 4.2 vs. 7.0 +/- 2.0 micrograms/mg creatinine, P less than 0.001).

An amino-terminal tetrapeptide specifies cotranslational degradation of beta-tubulin but not alpha-tubulin mRNAs.

The steady-state level of alpha- and beta-tubulin synthesis is autoregulated by a posttranscriptional mechanism that selectively alters alpha- and beta-tubulin mRNA levels in response to changes in the unassembled tubulin subunit concentration. For beta-tubulin mRNAs, previous efforts have shown that this is the result of a selective mRNA degradation mechanism which involves cotranslational recognition of the nascent amino-terminal beta-tubulin tetrapeptide as it emerges from the ribosome. Site-directed mutagenesis is now used to determine that the minimal sequence requirement for conferring the full range of beta-tubulin autoregulation is the amino-terminal tetrapeptide MR(E/D)I. Although tubulin-dependent changes in alpha-tubulin mRNA levels are shown to result from changes in cytoplasmic mRNA stability, transfection of wild-type and mutated alpha-tubulin genes reveals that alpha- and beta-tubulin mRNA degradation is not mediated through a common pathway. Not only does the amino-terminal alpha-tubulin tetrapeptide MREC fail to confer regulated mRNA degradation, neither wild-type alpha-tubulin transgenes nor an alpha-tubulin gene mutated to encode an amino-terminal MREI yields mRNAs that are autoregulated. Further, although slowing ribosome transit accelerates the autoregulated degradation of endogenous alpha- and beta-tubulin mRNAs, degradation of alpha-tubulin transgene mRNAs is not enhanced, and in one case, the mRNA is actually stabilized. We conclude that, despite similarities, alpha- and beta-tubulin mRNA destabilization pathways utilize divergent determinants to link RNA instability to tubulin subunit concentrations.

ArrayExpress--a public repository for microarray gene expression data at the EBI.

ArrayExpress is a public repository for microarray data that supports the MIAME (Minimum Information About a Microarray Experiment) requirements and stores well-annotated raw and normalized data. As of November 2004, ArrayExpress contains data from approximately 12,000 hybridizations covering 35 species. Data can be submitted online or directly from local databases or LIMS in a standard format, and password-protected access to prepublication data is provided for reviewers and authors. The data can be retrieved by accession number or queried by various parameters such as species, author and array platform. A facility to query experiments by gene and sample properties is provided for a growing subset of curated data that is loaded in to the ArrayExpress data warehouse. Data can be visualized and analysed using Expression Profiler, the integrated data analysis tool. ArrayExpress is available at http://www.ebi.ac.uk/arrayexpress.

Switching off and on of synaptic sites at aplysia sensorimotor synapses.

Using the highly plastic synapses between mechanoreceptor sensory neurons and siphon motor neurons of Aplysia as a model, we have investigated whether switching off and on of individual synaptic release sites is a strategy that is used by neurons in forms of short-term synaptic modulation with a time course of minutes to hours. We have modified some of the techniques of classical quantal analysis and examined the kinetics of synaptic depression under different stimulation protocols to answer this question. Our analysis shows that both synaptic depression caused by homosynaptic activity and synaptic facilitation induced by an endogenous facilitatory transmitter occur by means of the shutting off and turning on, respectively, of synaptic sites, without intermediate changes in the probability of release. Our findings imply that other forms of plasticity at these synapses, such as post-tetanic potentiation, long-term facilitation, and long-term potentiation, are also expressed by all-or-none changes in activity at individual sites. We thus show that in addition to the mechanisms of synaptic integration that are known to operate in single cells and networks, neurons can exercise a further layer of fine control, at the level of individual release sites.

Augmentation by chlorpropamide of 1-deamino-8-D-arginine vasopressin-induced antidiuresis and stimulation of renal medullary adenylate cyclase and accumulation of adenosine 3',5'-monophosphate.

The effect of chlorpropamide was determined in Brattleboro diabetes insipidus (DI) rats that were injected with 1-deamino-8-D-arginine vasopressin (dDAVP). Chlorpropamide augmented the antidiuretic responses to 0.78 and 1.56 ng dDAVP but not to larger doses. In an effort to explain this observation we investigated the effect of chlorpropamide on renal medullary adenylate cyclase activation by dDAVP and on phosphodiesterase activity. We found that the injection of chlorpropamide increased adenylate cyclase activation by dDAVP added in vitro to renal medullary cell membrane preparations from Brattleboro DI rats but had no effect on phosphodiesterase activity. When kidneys from Brattleboro DI rats, treated and not treated with chlorpropamide, were perfused in vitro, we found that 10(-4) M dDAVP increased the concentration of cAMP in comparison to untreated and chlorpropamide-treated groups, and that chlorpropamide plus dDAVP resulted in a greater concentration of renal cAMP than was found with dDAVP alone. We believe that treatment with chlorpropamide increases dDAVP-stimulated renal medullary adenylate cyclase activity without altering phosphodiesterase activity and that this leads to increased renal cAMP concentrations. This, in turn, causes an augmented antidiuresis in response to dDAVP.

Endocrine regulation of tissue glucose-6-phosphatase activity in the fetal sheep during late gestation.

Endocrine regulation of tissue glucose-6-phosphatase activity in utero was examined by measuring enzyme levels in liver and kidneys of fetal sheep during the second half of gestation and after experimental manipulation of fetal plasma cortisol and insulin levels. Tissue glucose-6-phosphatase activities increased toward term in parallel with the rise in fetal plasma cortisol. At birth, the activities were significantly higher than in utero, but significantly less than in adult nonpregnant sheep. Fetal hypophysectomy lowered fetal plasma cortisol and reduced hepatic and renal glucose-6-phosphatase activities compared with those in intact fetuses near term. Conversely, intrafetal cortisol infusion raised fetal plasma cortisol and significantly increased tissue glucose-6-phosphatase activity to values similar to those in older fetuses. When the data from these groups of fetuses and the newborn lambs were combined, there was a significant positive correlation between the plasma cortisol level and the glucose-6-phosphatase activity in both liver and kidney. Fetal hypoinsulinemia was induced by fasting the ewe for 48 h and by fetal pancreatectomy. Fetal hepatic and renal glucose-6-phosphatase activities were higher in fasted than in fed animals, while pancreatectomy had little apparent effect on enzyme activity in either tissue. However, when differences in plasma cortisol were taken into account, hepatic, but not renal, glucose-6-phosphatase activities were higher in both groups of hypoinsulinemic fetuses than would have been observed in normoinsulinemic animals with a similar plasma cortisol level. Partial correlation analysis of the data showed that plasma insulin and cortisol were both significant influences on hepatic glucose-6-phosphatase activity in utero, but plasma cortisol had the more pronounced effect. Cortisol, therefore, appears to be a physiological regulator of tissue glucose-6-phosphatase activity in utero and enhances the glucogenic capacity of the sheep fetus during late gestation.

Further studies on the mechanism by which chlorpropamide alters the action of vasopressin.

The injection of chlorpropamide into Brattleboro homozygous rats (di/di) has previously been shown to result in enhanced activation of renal medullary adenylate cyclase activity and increased renal medullary content of cAMP in response to 1-desamino-8-D-arginine vasopressin (dDAVP). In contrast, in vivo chlorpropamide did not alter GTP, guanylylimidodiphosphate, or fluoride-stimulated adenylate cyclase activities in these renal membranes. We have now found that the effect of in vivo chlorpropamide in enhancing dDVAP-stimulated adenylate cyclase activity involves lowering the Km for ATP. We have also found that dDAVP increases urinary prostaglandin E2 (PGE2) excretion, and treatment with chlorpropamide causes an even greater PGE2 response to dDAVP. In contrast, in vivo chlorpropamide treatment did not increase vascular responses to arginine vasopressin (AVP) in the perfused kidney preparation and, in fact, inhibited the AVP-induced decrease in the glomerular filtration rate. Chlorpropamide, therefore, enhances the renal responses to dDAVP in terms of the cAMP and PG systems, while not increasing responses to postreceptor stimuli of the adenylate cyclase system or vascular responses to AVP. These observations support the concept that in vivo chlorpropamide acts at the receptor of the vasopressin-sensitive part of the tubule to augment responsiveness to vasopressin. In addition, in vivo chlorpropamide may inhibit certain vascular responses to AVP.

Using 3' untranslated sequences to identify differentially expressed genes in Leishmania.

A more sensitive screen for Leishmania major genes differentially expressed as the insect stage develops into an infectious form (metacyclogenesis) has been devised. The screen expolits the observation that in kinetoplastid protozoa differentially expressed genes are often associated with unique 3' untranslated regions (UTRs). To obtain probes encoding this region, cDNA is synthesised using an oligo-dT primer containing the universal vectorette sequence in the first strand reaction and an oligonucleotide comprising the spliced leader sequence in the second strand reaction. The cDNAs are then cleaved with Sau3AI, ligated to the vectorette and the 3' UTRs polymerase chain reaction (PCR) amplified using the universal vectorette sequence as the primer. Differential screening with PCR-amplified 3' UTRs uncovered: (1) previously identified metacyclic-specific expressed genes; (2) cloned genes which had not been shown to be differentially regulated; and (3) a new gene identified only as a match to two identical L. major expressed sequence tags (ESTs) that is upregulated in the infectious stage.

Renal responses to PTH in patients with hormone-resistant (pseudo) hypoparathyroidism.

Five patients with pseudohypoparathyroidism were compared to normal subjects and patients with hypoparathyroidism in their ability to respond to the infusion of parathyroid hormone (PTH) by altering excretion of calcium, sodium, potassium, phosphate and bicarbonate. In patients with pseudohypoparathyroidism, impairment in renal responses to PTH was more generalized than has been recognized. The patterns of response varied from patient to patient. The most commonly observed abnormality, aside from lack of increase in urinary cyclic adenosine 5'-monophosphate (AMP) was failure to decrease the calcium to sodium clearance ratio, and indication of impaired renal calcium reabsorption. The responses which most closely approximated normal, including a normal decrease in the calcium to sodium clearance ratio, occurred in a patient (Case 1) who had the largest, although impaired, response in cyclic AMP excretion. Conversely, the most abnormal responses occurred in three patients (Cases 2, 4 and 5) who had the smallest increases in cyclic AMP excretion after the administration of PTH. The impaired renal reabsorption of calcium after the administration of PTH (lack of decrease in calcium to sodium clearance ratio) may, when present, be in part responsible for hypocalcemia.

Isolation of genes showing increased or unique expression in the infective promastigotes of Leishmania major.

The trypanosomatid parasite Leishmania major is one of the principal causal agents of human cutaneous leishmaniasis. Promastigotes grown in vitro undergo growth cycle-dependent differentiation, associated with morphological and biochemical changes, to produce forms which are infective to the mammalian host. By differentially screening a cDNA library constructed from stage-specific mRNA, we have isolated 4 clones encoding mRNAs which show unique or elevated expression in the infective promastigotes of Leishmania major. One of these clones is homologous to a heat-shock protein 70-related gene, that is non-heat-inducible but shows up-regulation during promastigote differentiation. Each of the other cDNAs isolated also recognises multiple transcripts, which show differential regulation between parasite stages and are encoded by repeated, linked nuclear genes. In trypanosomatids, this genomic organisation is indicative of polycistronic transcription.

Differential expression of Leishmania major beta-tubulin genes during the acquisition of promastigote infectivity.

Tubulin expression has been analysed as the insect stage of the protozoan parasite Leishmania major differentiates from a non-infective to an infective form. This transformation of the promastigote stage occurs in vitro and analysis of beta-tubulin mRNA expression in axenically grown promastigotes showed that a 2200 nt transcript is predominately expressed in non-infective promastigotes. The message contains a motif associated with mRNA intracellular localisation and its level is reduced by an order of magnitude in infective promastigotes through a mechanism involving RNA stability. A 3200 nt RNA, the major beta-tubulin transcript in the infective stage, is encoded by a single copy gene at the 3' end of the array that encodes the 2200 nt RNA. These RNAs, as well as a gene encoding a beta-tubulin transcript highly up-regulated in the mammalian stage of the parasite, encode polypeptides that are apparently functionally equivalent but have highly diverged 3' untranslated regions. This differential regulation of the dispersed isogenes may reflect the involvement of a mechanism altering tubulin synthesis during the Leishmania life cycle. The analysis of alpha-tubulin RNA levels revealed the abundance of this message falls as promastigotes differentiate into an infectious stage and the transcript is destabilised in infective promastigotes. These data demonstrate that the regulation of mRNA half-life contributes to controlling gene expression as promastigotes differentiate into an infectious form.

Discrepancy in stoichiometry of steady-state muscle [Pi] and [PCr] induced by exercise.

Phosphorus nuclear magnetic resonance was used to quantify the relations between metabolic phosphates, intracellular pH, and work rate in forearm muscle of six adult men over a range of work rates from 1.0 to 3.5 W. Three work rates were studied in each of four sessions (either 1.0, 2.0, and 3.0 or 1.5, 2.5, and 3.5 W), with measurements made before and during each bout, thereby permitting the partition of the variance attributable to rest, work-dependent, and time-dependent metabolic functions by regression analysis. There were no time-dependent changes in either [ATP] or intracellular [H+] as assessed during the rest intervals between bouts of exercise. In contrast, the total nuclear magnetic resonance (NMR)-visible phosphorus pool (TVPP) decreased with time, with both phosphocreatine (PCr) and inorganic phosphate (Pi) contributing significantly to TVPP reduction. Muscle [ATP] was unchanged by work at all intensities. Intracellular [H+] increased moderately and proportionately to work rate. [PCr] decreased and [Pi] increased in proportion to work rate, with the work-dependent coefficient for PCr consumption approximately 1.5 times that of Pi production. Neither Pi line width nor motion artifact accounted for the decrease in TVPP, so the reduced Pi accumulation in exercise may represent its sequestering in some NMR-invisible muscle pool and/or loss to the blood. Whatever the process involved, it is proportional to work rate and persists for at least 10-15 min after exercise.

In vivo 31P-NMR in human muscle: transient patterns with exercise.

Evaluation of dynamic changes in pH and concentrations of adenosine 5'-triphosphate (ATP), phosphocreatine (PCr), and inorganic phosphate (Pi) during the transition from rest to steady-state exercise in the human has been methodologically limited. Previous work has relied on muscle biopsy of exercising subjects at different times in different exercise bouts. Chemical evaluation of metabolites has been hampered by continuing change in metabolic concentration during the biopsy procedure. Recently, Fourier-transformed 31P nuclear magnetic resonance (31P-NMR), employing surface coils, has made evaluation of phosphorus metabolites possible by noninvasive atraumatic means in human muscle. Relative concentrations of PCr, Pi, and ATP, together with pH, have been obtained with 31P-NMR from the flexor digitorum superficialis muscle on two occasions in four adult men during the transition from rest to exercise. [PCr] rapidly fell and was mirrored by a rise in [Pi]. The former temporarily exceeded the latter with the discrepancy apparently being absorbed by a transient rise in [ATP], which was itself mirrored by alteration in [H+].

Cytochalasin D inhibits penetration of hamster eggs by guinea pig and human spermatozoa.

Fertilization experiments using zona-free hamster eggs and spermatozoa from both guinea pig and human were conducted in the presence of cytochalasin D to evaluate the possible role of actin filaments in fertilization processes. When the actin filament inhibitor, cytochalasin D, was added to fertilization media at concentrations of 10 to 30 microM, penetration of eggs was significantly inhibited. Preincubation of the eggs with cytochalasin D and washing prior to addition of spermatozoa had no effect on penetration as quantitated by the number of swollen heads in the egg cytoplasm. However, spermatozoa preincubated with cytochalasin D and subsequently washed prior to egg addition showed reduced penetration of the same magnitude as when spermatozoa and eggs were coincubated with cytochalasin D. Both the percentage of zona-free eggs showing decondensed sperm heads and the penetration indices (total decondensed spermatozoa/total eggs) were significantly affected when spermatozoa were exposed to cytochalasin D. The DMSO vehicle used to dissolve cytochalasin D had little effect on the number of decondensed heads. When the concentration of cytochalasin D was increased (DMSO remaining constant) in human sperm experiments, percent penetration decreased and progressively fewer decondensed spermatozoa were recorded, indicating dose-responsiveness to cytochalasin D. Motility parameters of human spermatozoa were not altered at any of the concentrations of cytochalasin D tested. Neither guinea pig sperm motility nor acrosome reaction was altered significantly by cytochalasin D or the DMSO vehicle. These experiments suggest that cytochalasin D may be an inhibitor of some fertilization processes such as sperm penetration or sperm head decondensation.

A survey of medical school teachers to identify basic biomedical concepts medical students should understand.

Insights from the cognitive sciences indicate a continuing need for physicians to understand conceptual knowledge from the basic sciences, despite recent concerns regarding the increasing amount of information in medicine and the growing emphasis on performance skills. A 1987 survey of selected basic science and clinical teachers in North American medical schools was undertaken to identify basic biomedical concepts that are important in the practice of medicine and to specify how difficult these are for students to learn, apply, or both. Responses from faculty (nominated by their deans to answer the survey) from 82% of the medical schools indicated considerable agreement between the basic science teachers and clinical teachers on the relative importance of a set of biomedical concepts, and showed relatively minor levels of disagreement on how difficult these concepts are. The judgments of these teachers could prove extremely useful in (1) determining concepts that--because of their importance--should receive special attention in curriculum efforts, and (2) determining concepts that--because of their difficulty--need "special handling."