Stochastic particle barcoding for single-cell tracking and multiparametric analysis.

This study presents stochastic particle barcoding (SPB), a method for tracking cell identity across bioanalytical platforms. In this approach, single cells or small collections of cells are co-encapsulated within an enzymatically-degradable hydrogel block along with a random collection of fluorescent beads, whose number, color, and position encode the identity of the cell, enabling samples to be transferred in bulk between single-cell assay platforms without losing the identity of individual cells. The application of SPB is demonstrated for transferring cells from a subnanoliter protein secretion/phenotyping array platform into a microtiter plate, with re-identification accuracies in the plate assay of 96±2%. Encapsulated cells are recovered by digesting the hydrogel, allowing subsequent genotyping and phenotyping of cell lysates. Finally, a model scaling is developed to illustrate how different parameters affect the accuracy of SPB and to motivate scaling of the method to thousands of unique blocks.

Alcohol and male reproductive health: a cross-sectional study of 8344 healthy men from Europe and the USA.

STUDY QUESTION: Is there an association between alcohol intake and semen quality and serum reproductive hormones among healthy men from the USA and Europe? SUMMARY ANSWER: Moderate alcohol intake is not adversely associated with semen quality in healthy men, whereas it was associated with higher serum testosterone levels. WHAT IS KNOWN ALREADY: High alcohol intake has been associated with a wide range of diseases. However, few studies have examined the correlation between alcohol and reproductive function and most have been conducted in selected populations of infertile men or have a small sample size and the results have been contradictory. STUDY DESIGN, SIZE, DURATION: A coordinated international cross-sectional study among 8344 healthy men. A total of 1872 fertile men aged 18-45 years (with pregnant partners) from four European cities and four US states, and 6472 young men (most with unknown fertility) aged 18-28 years from the general population in six European countries were recruited. PARTICIPANTS/MATERIALS, SETTING, METHODS: The men were recruited using standardized protocols. A semen analysis was performed and men completed a questionnaire on health and lifestyle, including their intake of beer, wine and liquor during the week prior to their visit. Semen quality (semen volume, sperm concentration, percentage motile and morphologically normal sperm) and serum reproductive hormones (FSH, LH, testosterone, sex hormone-binding globulin, and inhibin B and free testosterone) were examined. MAIN RESULTS AND THE ROLE OF CHANCE: The participation rate for our populations was 20-30%. We found no consistent association between any semen variable and alcohol consumption, which was low/moderate in this group (median weekly intake 8 units), either for total consumption or consumption by type of alcohol. However, we found a linear association between total alcohol consumption and total or free testosterone in both groups of men. Young and fertile men who consumed >20 units of alcohol per week had, respectively, 24.6 pmol/l (95% confidence interval 16.3-32.9) and 19.7 pmol/l (7.1-32.2) higher free testosterone than men with a weekly intake between 1 and 10 units. Alcohol intake was not significantly associated with serum inhibin B, FSH or LH levels in either group of men. The study is the largest of its kind and has sufficient power to detect changes in semen quality and reproductive hormones. LIMITATIONS, REASONS FOR CAUTION: The participation rate was low, but higher than in most previous semen quality studies. In addition, the study was cross-sectional and the men were asked to recall their alcohol intake in the previous week, which was used as a marker of intake up to 3 months before. If consumption in that week differed from the typical weekly intake and the intake 3 months earlier, misclassification of exposure may have occurred. However, the men were unaware of their semen quality when they responded to the questions about alcohol intake. Furthermore, we cannot exclude that our findings are due to unmeasured confounders, including diet, exercise, stress, occupation and risk-taking behavior. WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that moderate alcohol intake is not adversely associated with semen quality in healthy men, whereas it was associated with higher serum testosterone levels which may be due to a changed metabolism of testosterone in the liver. Healthy men may therefore be advised that occasional moderate alcohol intake may not harm their reproductive health; we cannot address the risk of high alcohol consumption of longer duration or binge drinking on semen quality and male reproductive hormones. STUDY FUNDING/COMPETING INTERESTS: All funding sources were non-profitable and sponsors of this study played no role in the study design, in data collection, analysis, or interpretation, or in the writing of the article. The authors have no conflicts of interest.

Is γ-ray emission from novae affected by interference effects in the 18F(p,α)15O reaction?

The (18)F(p,α)(15)O reaction rate is crucial for constraining model predictions of the γ-ray observable radioisotope (18)F produced in novae. The determination of this rate is challenging due to particular features of the level scheme of the compound nucleus, (19)Ne, which result in interference effects potentially playing a significant role. The dominant uncertainty in this rate arises from interference between J(π)=3/2(+) states near the proton threshold (S(p)=6.411 MeV) and a broad J(π)=3/2(+) state at 665 keV above threshold. This unknown interference term results in up to a factor of 40 uncertainty in the astrophysical S-factor at nova temperatures. Here we report a new measurement of states in this energy region using the (19)F((3)He,t)(19)Ne reaction. In stark contrast to previous assumptions we find at least 3 resonances between the proton threshold and E(cm)=50 keV, all with different angular distributions. None of these are consistent with J(π)=3/2(+) angular distributions. We find that the main uncertainty now arises from the unknown proton width of the 48 keV resonance, not from possible interference effects. Hydrodynamic nova model calculations performed indicate that this unknown width affects (18)F production by at least a factor of two in the model considered.

Classical-NOVA CONTRIBUTION to the Milky Way's ²6Al abundance: exit channel of the key ²5Al(p,γ) ²6Si resonance.

Classical novae are expected to contribute to the 1809-keV Galactic γ-ray emission by producing its precursor 26Al, but the yield depends on the thermonuclear rate of the unmeasured 25Al(p,γ)26Si reaction. Using the ß decay of 26P to populate the key J(π)=3(+) resonance in this reaction, we report the first evidence for the observation of its exit channel via a 1741.6±0.6(stat)±0.3(syst) keV primary γ ray, where the uncertainties are statistical and systematic, respectively. By combining the measured γ-ray energy and intensity with other experimental data on 26Si, we find the center-of-mass energy and strength of the resonance to be E(r)=414.9±0.6(stat)±0.3(syst)±0.6(lit.) keV and ωγ=23±6(stat)(-10)(+11)(lit.) meV, respectively, where the last uncertainties are from adopted literature data. We use hydrodynamic nova simulations to model 26Al production showing that these measurements effectively eliminate the dominant experimental nuclear-physics uncertainty and we estimate that novae may contribute up to 30% of the Galactic 26Al.

Upstream Dispersion in Solute Transport Models: A Simple Evaluation and Reduction Methodology.

This article outlines analytical solutions to quantify the length scale associated with "upstream dispersion," the artificial movement of solutes in the opposite direction to groundwater flow, in solute transport models. Upstream dispersion is an unwanted artifact in common applications of the advection-dispersion equation (ADE) in problems involving groundwater flow in the direction of increasing solute concentrations. Simple formulae for estimating the one-dimensional distance of upstream dispersion are provided. These show that under idealized conditions (i.e., steady-state flow and transport, and a homogeneous aquifer), upstream dispersion may be a function of only longitudinal dispersivity. The scale of upstream dispersion in a selection of previously presented situations is approximated to highlight the utility of the presented formulae and the relevance of this ADE anomaly in common transport problems. Additionally, the analytical solution is applied in a hypothetical scenario to guide the modification of dispersion parameters to minimize upstream dispersion.

Severe and extensive neonatal hearing loss in cats results in auditory cortex plasticity that differentiates into two regions.

We examined the response characteristics of primary auditory cortex (A1) neurons in adult cats partially but extensively deafened by ototoxic drugs 2-8 days after birth. The damage evoked extensive A1 topographic map reorganization as also found by others, but a novel finding was that in the majority of cats with low-frequency edges to the cochlear lesion, the area of reorganization segregated into two areas expressing the same novel frequency inputs but differentiated by neuronal sensitivity and responsiveness. Immediately adjacent to normal A1 is an approximately 1.2-mm-wide area of reorganization in which sensitivity and responsiveness to sound are similar to that in normal A1 in the same animals and in unlesioned adult animals. Extending further into deprived A1 is a more extensive area of reorganization where neurons have poorer sensitivity and responsiveness to new inputs. These two areas did not differ in response-area bandwidth and response latency. We interpret these novel changes as the cortical consequences of severe receptor organ lesions extending to low-frequency cochlear regions. We speculate that the two areas of A1 reorganization may reflect differences in the transcortical spatial distribution of thalamo-cortical and horizontal intracortical connections. Qualitatively similar changes in response properties have been seen after retinal lesions producing large areas of visual cortical reorganization, suggesting they might be a general consequence of receptor lesions that deprive large regions of cortex of normal input. These effects may have perceptual implications for the use of cochlear implants in patients with residual low-frequency hearing.

Lack of impact of semen quality on fertilization in assisted conception.

BACKGROUND: Defective semen quality is one of the commonest causes of infertility. The diagnosis of male fertility depends upon a descriptive evaluation of human semen, however a normal semen analysis does not necessarily indicate satisfactory fertility potential. AIMS: (i) to examine the semen quality of patients undergoing treatment by assisted conception, (ii) to explore relationships between semen quality and treatment outcomes, and (iii) to look at inter-laboratory variation in the assessment of semen quality. METHODS: Semen quality in patients undergoing assisted conception treatment between 2001 and 2004 was reviewed. Data on female age, egg numbers and fertilization outcomes was obtained by case note review. RESULTS: The thresholds used to direct patients towards IVF or ICSI treatment were comparable with the normal values promulgated by WHO, with the exception of morphology. Semen quality was not predictive of fertilization rates. When the results of independent measurements of the same sample were compared, there was diagnostic disagreement in between 10%-29% of samples. CONCLUSIONS: The conventional criteria of semen quality are used to determine treatment strategy for couples undergoing assisted conception but are not reflected in fertilization rates, emphasising the limited utility of the conventional criteria of semen quality in the assessment of sperm function. There remains significant inter-laboratory variation in the results of semen analysis.

Centromere protein B null mice are mitotically and meiotically normal but have lower body and testis weights.

CENP-B is a constitutive centromere DNA-binding protein that is conserved in a number of mammalian species and in yeast. Despite this conservation, earlier cytological and indirect experimental studies have provided conflicting evidence concerning the role of this protein in mitosis. The requirement of this protein in meiosis has also not previously been described. To resolve these uncertainties, we used targeted disruption of the Cenpb gene in mouse to study the functional significance of this protein in mitosis and meiosis. Male and female Cenpb null mice have normal body weights at birth and at weaning, but these subsequently lag behind those of the heterozygous and wild-type animals. The weight and sperm content of the testes of Cenpb null mice are also significantly decreased. Otherwise, the animals appear developmentally and reproductively normal. Cytogenetic fluorescence-activated cell sorting and histological analyses of somatic and germline tissues revealed no abnormality. These results indicate that Cenpb is not essential for mitosis or meiosis, although the observed weight reduction raises the possibility that Cenpb deficiency may subtly affect some aspects of centromere assembly and function, and result in reduced rate of cell cycle progression, efficiency of microtubule capture, and/or chromosome movement. A model for a functional redundancy of this protein is presented.

The use of graft copolymers to bind immiscible blends.

Computer simulations and experimental studies were combined to design copolymers that enhance the strength of polymer composites. These copolymers contain side chains that associate across the boundary between phase-separated regions to form a "molecular velcro" that effectively binds the regions together. This behavior significantly improves the structural integrity and mechanical properties of the material. Because the side chains can be fabricated from a large class of compounds, the technique greatly increases the variety of copolymers that can be used in forming high-strength polymer blends.

A Comparison of SIR-B Directional Ocean Wave Spectra with Aircraft Scanning Radar Spectra.

Directional ocean wave spectra derived from Shuttle Imaging Radar-B (SIR-B) L-band imagery collected off the coast of southern Chile on 11 and 12 October 1984 were compared with independent spectral estimates from two airborne scanning radars. In sea states with significant wave heights ranging from 3 to 5 meters, the SIR-B-derived spectra at 18 degrees and 25 degrees off nadir yielded reasonable estimates of wavelengths, directions, and spectral shapes for all wave systems encountered, including a purely azimuth-traveling system. A SIR-B image intensity variance spectrum containing predominantly range-traveling waves closely resembles an independent aircraft estimate of the slope variance spectrum. The prediction of a U.S. Navy global spectral ocean wave model on 11 October 1984 exhibited no significant bias in dominant wave number but contained a directional bias of about 30 degrees espect to the mean of the aircraft and spacecraft estimates.

Improved Vertical Streambed Flux Estimation Using Multiple Diurnal Temperature Methods in Series.

Analytical solutions that use diurnal temperature signals to estimate vertical fluxes between groundwater and surface water based on either amplitude ratios (Ar ) or phase shifts (Δϕ) produce results that rarely agree. Analytical solutions that simultaneously utilize Ar and Δϕ within a single solution have more recently been derived, decreasing uncertainty in flux estimates in some applications. Benefits of combined (Ar Δϕ) methods also include that thermal diffusivity and sensor spacing can be calculated. However, poor identification of either Ar or Δϕ from raw temperature signals can lead to erratic parameter estimates from Ar Δϕ methods. An add-on program for VFLUX 2 is presented to address this issue. Using thermal diffusivity selected from an Ar Δϕ method during a reliable time period, fluxes are recalculated using an Ar method. This approach maximizes the benefits of the Ar and Ar Δϕ methods. Additionally, sensor spacing calculations can be used to identify periods with unreliable flux estimates, or to assess streambed scour. Using synthetic and field examples, the use of these solutions in series was particularly useful for gaining conditions where fluxes exceeded 1 m/d.

SELEXION. Systematic evolution of ligands by exponential enrichment with integrated optimization by non-linear analysis.

Recently, novel technologies for isolation of nucleic acid molecules with specific biological activities have been reported. In each case, the enrichment process involves repeated rounds of selection from complex mixtures of nucleic acid sequences, followed by polymerase chain reaction (PCR) amplification of ligand sequences that function in the desired manner. Particular variations in experimental conditions can dramatically alter the outcome of these processes. In this study, we use mathematical analysis and computer simulation to predict which variations have the greatest impact and to develop strategies and guidelines for enhanced effectiveness. First, we perform reconstruction tests to demonstrate that a mathematical description based on equilibrium binding is sufficient to explain the high levels of enrichment attained in the laboratory after just a few rounds. Then, we show the expected enrichment for an extensive range of conditions; and, finally, we determine the optimum protein and nucleic acid concentrations to use for maximum enrichment, while also ensuring a high likelihood of recovering even the rare molecule that binds well. The strategies and guidelines for enhanced effectiveness are generally applicable to processes for systematic enrichment of DNA, RNA or peptide ligands and have been implemented in an interactive simulation program for integrated non-linear optimization of enrichment using any target of interest.

Embryonic expression and activity of doughnut, a second RYK homolog in Drosophila.

In the Drosophila embryo, a subset of muscles require expression and function of the RYK subfamily RTK gene derailed (drl) for correct attachment. We have isolated a second RYK homolog, doughnut (dnt), from Drosophila. The DNT protein exhibits 60% amino acid identity to DRL, and is structurally as similar to the mammalian RYK proteins as is DRL, indicating an ancient duplication event. dnt is expressed in dynamic patterns in the embryonic epidermis, being found at high level in epithelia adjacent to cells that are invaginating into the interior of the embryo, including ventral furrow, cephalic furrow, fore- and hindgut, optic lobe and tracheal pits. dnt is capable of a partial rescue of the muscle attachment defect of drl-/- embryos, indicating that it encodes a receptor with a related and significantly overlapping biochemical function.

The influence of dispersant concentration on the pore morphology of hydroxyapatite ceramics for bone tissue engineering.

There is a clinical need for synthetic scaffolds that will promote bone regeneration. Important factors include obtaining an optimal porosity and size of interconnecting windows whilst maintaining scaffold mechanical strength, enabling complete penetration of cells and nutrients throughout the scaffold, preventing the formation of necrotic tissue in the centre of the scaffold. To address this we investigated varying slip deflocculation in order to control the resulting porosity, pore size and interconnecting window size whilst maintaining mechanical strength. Hydroxyapatite (HA) porous ceramics were prepared using a modified slip casting process. Rheological measurements of the HA slips were used to identify deflocculation conditions which resulted in changes in the cell and window sizes of the resulting ceramics. Sintered ceramics were characterised by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Pore and window size distribution was determined by SEM. XRD analysis confirmed that the crystal structure remained HA after the sintering process. SEM showed that HA porous ceramics presented a highly interconnected porous network with average pore sizes ranging from 391+/-39 to 495+/-25 microm. The average window size varied from 73+/-5 to 135+/-7 microm. Pore diameters obtained were controllable in the range 200-500 microm. Window sizes were in the range 30-250 microm. The use of dispersant concentration allows pore and window size to be modified whilst maintaining control over porosity demonstrated by a porosity of 85% for seven different dispersant concentrations. The advantage of this approach allows the correlation between the rheological conditions of the slip and the resultant sintered ceramic properties. In particular, optimising the ceramic strength by controlling the agglomeration during the casting process.

Brown recluse spider bites: a complex problem wound. A brief review and case study.

Brown recluse spiders (Loxosceles reclusa) are responsible for virtually all documented cases of spider bites leading to significant necrosis. The actual spider bite often goes unnoticed for as long as 4 to 6 hours, which makes diagnosis and, therefore, appropriate treatment, difficult. The spider bite generally results in either a necrotic wound or systemic symptoms that can lead to hemolysis. The patient described in this article experienced both complications. Dapsone and hyperbaric oxygen therapy brought the adverse response to the bite under control. The patient was hospitalized for 7 days during treatment for hemolysis and an extensive, necrotic wound. Efforts are underway to develop an assay to provide a definitive diagnosis for the brown recluse spider bite, but none is yet commercially available. Antivenom is scarce; capture of the offending spider appears to be most helpful in the diagnosis and proper treatment of spider bites.

Optimizing geometric accuracy of four-dimensional CT scans acquired using the wall- and couch-mounted Varian® Real-time Position Management™ camera systems.

OBJECTIVE: The aim of this study was to identify sources of anatomical misrepresentation owing to the location of camera mounting, tumour motion velocity and image processing artefacts in order to optimize the four-dimensional CT (4DCT) scan protocol and improve geometrical-temporal accuracy. METHODS: A phantom with an imaging insert was driven with a sinusoidal superior-inferior motion of varying amplitude and period for 4DCT scanning. The length of a high-density cube within the insert was measured using treatment planning software to determine the accuracy of its spatial representation. Scan parameters were varied, including the tube rotation period and the cine time between reconstructed images. A CT image quality phantom was used to measure various image quality signatures under the scan parameters tested. RESULTS: No significant difference in spatial accuracy was found for 4DCT scans carried out using the wall- or couch-mounted camera for sinusoidal target motion. Greater spatial accuracy was found for 4DCT scans carried out using a tube rotation speed of 0.5 s rather than 1.0 s. The reduction in image quality when using a faster rotation speed was not enough to require an increase in patient dose. CONCLUSION: The 4DCT accuracy may be increased by optimizing scan parameters, including choosing faster tube rotation speeds. Peak misidentification in the recorded breathing trace may lead to spatial artefacts, and this risk can be reduced by using a couch-mounted infrared camera. ADVANCES IN KNOWLEDGE: This study explicitly shows that 4DCT scan accuracy is improved by scanning with a faster CT tube rotation speed.

The extragenomic action of progesterone on human spermatozoa: evidence for a ubiquitous response that is rapidly down-regulated.

Image analysis techniques have been used to demonstrate that progesterone induces a rapid calcium transient in the acrosomal domain of greater than 90% of human spermatozoa (n = 2354). These results are at variance with previous reports, suggesting that progesterone receptors are only expressed on a small subpopulation of these cells, by virtue of their ability to bind fluorescent probes incorporating progesterone 3- (O-carboxymethyl) oxime conjugated to BSA. In the present study, we could confirm that such probes only bound to a small proportion of human spermatozoa (3.01 +/- 0.29%; n = 7557) although 91.79 +/- 1.8% of the same sperm populations exhibited a calcium transient in response to progesterone. These results indicate that the binding of labeled progesterone conjugates to human spermatozoa does not reflect the size of the progesterone responsive population; the response elicited by this steroid is essentially ubiquitous. Progesterone action was shown to involve an influx of extracellular calcium via mechanisms that did not involve voltage sensitive- or second messenger operated-channels, phospholipase C, or G proteins. Despite previous evidence suggesting that progesterone action might involve a GABAA receptor/chloride channel, neither GABA nor the GABA agonist muscimol had any effect on intracellular calcium concentrations in human spermatozoa or influenced their functional competence. The only factor that disrupted the responses of human spermatozoa to progesterone was this steroid itself. Progesterone exposure induced a prolonged period of refractoriness to further stimulation that influenced the capacity of these cells to generate calcium transients, and their ability to exhibit a biological response to changes in intracellular calcium. There are implications in these results for our understanding of the extragenomic action of progesterone on human spermatozoa and the clinical manipulation of this system for the assessment and suppression of human sperm function.

ERbeta1 and the ERbeta2 splice variant (ERbetacx/beta2) are expressed in distinct cell populations in the adult human testis.

Estrogens can regulate germ cell function. Estrogen action is mediated via high affinity ERs; two subtypes (ERalpha and ERbeta) have been identified. We have shown previously that ERbeta is expressed in nuclei of multiple human testicular cells. A variant isoform of human (h) ERbeta (hERbetacx/2), formed by alternative splicing, has been identified in testicular cDNA libraries by two laboratories. The present study examined the expression of wild-type (ERbeta1) and variant (ERbeta2) beta receptors in human testes by 1) RT-PCR with isoform specific primers, and 2) single and double immunohistochemistry using monoclonal antibodies raised against peptides unique to the C termini of hERbeta1 and hERbeta2. PCR products specific for ERbeta1 and ERbeta2 were amplified from cDNA pools prepared from human testes and granulosa cells. On Western blots, the anti-ERbeta1 monoclonal antibody bound to recombinant ERbeta1 and the anti-ERbeta2 monoclonal to recombinant hERbeta2. Neither bound to the other ERbeta isoform nor to recombinant ERalpha. ERbeta1 and ERbeta2 proteins were both detected in human testis. Immunoexpression of ERbeta1 was most intense in pachytene spermatocytes and round spermatids, whereas low levels of expression were detected in Sertoli cells, spermatogonia, preleptotene, leptotene, zygotene, and diplotene spermatocytes. Highest levels of expression of ERbeta2 protein were detected in Sertoli cells and spermatogonia with low/variable expression in preleptotene, pachytene, and diplotene spermatocytes. No immunostaining was detected in elongating spermatids. Most interstitial cells expressed more ERbeta2 than ERbeta1. It is speculated that the cells most susceptible to modulation by estrogenic ligands are round spermatids in which levels of expression of ERbeta1 are high. In contrast, expression of ERbeta2, an isoform that may act as a dominant negative inhibitor of ER action, in Sertoli cells and spermatogonia, could protect these cells from adverse effects of estrogens.

Superoxide dismutase in human sperm suspensions: relationship with cellular composition, oxidative stress, and sperm function.

Sensitive techniques have been developed for monitoring superoxide dismutase (SOD) activities in human sperm preparations. In contradiction to the protective role normally assigned to SOD, populations of defective spermatozoa recovered from the low density region of Percoll gradients were found to have three times more SOD than functionally competent preparations pelleting in high density Percoll. SOD activity was negatively correlated with the movement characteristics of human spermatozoa and their capacity for oocyte fusion, and positively associated with the induction of peroxidative damage. SOD activity was also highly correlated with other markers of the cytoplasmic space, creatine kinase (CK), and glucose-6-phosphate dehydrogenase (G-6-PDH). We conclude that while SOD may play a physiological role in maintaining a balance between O2.- and H2O2, high levels of this enzyme are associated with impaired sperm function because (a) the human spermatozoon is highly susceptible to the cytotoxic effects of H2O2, (b) O2.- is an important mediator of normal sperm function, and (c) high SOD activities reflect errors in spermatogenesis associated with germ cell exfoliation and the retention of excess residual cytoplasm by the spermatozoa.

Plasticity of frequency organization in auditory cortex of guinea pigs with partial unilateral deafness.

We have examined the effect of restricted unilateral cochlear lesions on the orderly topographic mapping of sound frequency in the auditory cortex of adult guinea pigs. These lesions, although restricted in spatial extent, resulted in a variety of patterns of histological damage to receptor cells and nerve fibres within the cochlea. Nevertheless, all lesions resulted in permanent losses of sensitivity of the cochlear neural output across a limited frequency range. Thirty-five to 81 days after such damage to the organ of Corti, the area of contralateral auditory cortex in which the lesioned frequency range would normally have been represented was partly occupied by an expanded representation of sound frequencies adjacent to the frequency range damaged by the lesion. The thresholds at their new characteristic frequencies (CFs) of clusters of cortical neurones in these regions were close to normal thresholds at those frequencies (mean difference across all animals was 3.8 dB). In a second series of experiments, the responses of neurone clusters were examined within hours of making similar cochlear lesions. It was found that shifts in CF toward frequencies spared by the lesions could occur, but thresholds were greatly elevated compared to normal (mean difference was 31.7 dB in five animals). The emergence of sensitive drive in such regions after prolonged recovery periods in lesioned animals thus suggests that the auditory cortical frequency map undergoes reorganization in cases of partial deafness. Some features of this reorganization are similar to changes reported in somatosensory cortex after peripheral nerve injury, and this form of plasticity may therefore be a feature of all adult sensory systems.