Response variability in the mammalian auditory cortex: an objection to feature detection?

Research strategy in the auditory system has tended to parallel that in the visual system, where neurons have been shown to respond selectively to specific stimulus parameters. Auditory neurons have been shown to be sensitive to changes in acoustic parameters, but only rarely have neurons been reported that respond exclusively to only one biologically significant sound. Even at higher levels of the auditory system very few cells have been found that could be described as "vocalization detectors." In addition, variability in responses to artificial sounds have been reported for auditory cortical neurons similar to the response variability that has been reported in the visual system. Recent evidence indicates that the responses of auditory cortical neurons to species-specific vocalizations can also be labile, varying in both strength and selectivity. This is especially true of the secondary auditory cortex. This variability, coupled with the lack of extreme specificity in the secondary auditory cortex, suggests that secondary cortical neurons are not well suited for the role of "vocalization detectors."     

Structures of low molecular weight inhibitors bound to MDMX and MDM2 reveal new approaches for p53-MDMX/MDM2 antagonist drug discovery

Intensive anticancer drug discovery efforts have been made to develop small molecule inhibitors of the p53-MDM2 and p53-MDMX interactions. We present here the structures of the most potent inhibitors bound to MDM2 and MDMX that are based on the new imidazo-indole scaffold. In addition, the structure of the recently reported spiro-oxindole inhibitor bound to MDM2 is described. The structures indicate how the substituents of a small molecule that bind to the three subpockets of the MDM2/X-p53 interaction should be optimized for effective binding to MDM2 and/or MDMX. While the spiro-oxindole inhibitor triggers significant ligand-induced changes in MDM2, the imidazo-indoles share similar binding modes for MDMX and MDM2, but cause only minimal induced-fit changes in the structures of both proteins. Our study includes the first structure of the complex between MDMX and a small molecule and should aid in developing efficient scaffolds for binding to MDMX and/or MDM2.     

On-line evaluation of ultrasonic integrated backscatter

Although it is already known that reflected ultrasonic signals (backscatter) are changed by the structure of the tissue through which they pass, clinicians are still awaiting a practical instrument in which information from backscatter reflections will serve as a diagnostic aid additional to that provided by conventional ultrasonic scans.The equipment described here is both small and fast, and is integrated into a normal ultrasound installation. No new operating procedures have to be learned. The integrated backscatter is calculated on-line and presented on an LED as tissue characterization parameters. In order to minimize noise due to physical movement of the heart during an investigation of the myocardium, the analysis is synchronized with the ECG; and as an aid to the user, the normal system VDU displays both the ECG and the activating trigger pulse derived from the R-wave peak. An A-scan display has been used but this could readily be adapted for B-scan operation and single line analysis.Tests with backscattering models and standard instrumentation have shown no significant difference between results using time domain or frequency domain analysis.     

Chrysochromulina laurentiana: an electron microscopic study of a new species of Prymnesiophyceae from Canadian Shield lakes

Three species of Chrysochromulina have been observed from the plankton of Canadian Shield lakes of the Experimental Lakes Area, northwestern Ontario. Chrysochromulina parva Lackey is ubiquitous and well known. C. breviturrita Nicholls and C. laurentiana described here appear similar to one another under the light microscope, but with the aid of the transmission electron microscope it is possible to distinguish them as two different species.     

Can Molecular Imprinting Explain Heterozygote Deficiency and Hybrid Vigor?

Molecular imprinting, the phenomenon of differential expressions of a gene based on whether it is paternally or maternally derived, has been noted in mice, humans, and other nonmammalian organisms. Effects of differential imprinting are important not only in the study of the manifestation of deleterious genes; they have important evolutionary implications as well. It is shown here that molecular imprinting may mimic observations that are often construed to be due to hybrid vigor and/or inbreeding depression. Furthermore, if a locus undergoes differential imprinting, it also yields observed genotypic proportions which mimic heterozygote deficiency in the population without the aid of natural selection.     

Everything’s Relative? Relative Differences in Processing Fluency and the Effects on Liking

Explanations of aesthetic pleasure based on processing fluency have shown that ease-of-processing fosters liking. What is less clear, however, is how processing fluency arises. Does it arise from a relative comparison among the stimuli presented in the experiment? Or does it arise from a comparison to an internal reference or standard? To address these questions, we conducted two experiments in which two ease-of-processing manipulations were applied: either (1) within-participants, where relative comparisons among stimuli varying in processing ease were possible, or (2) between-participants, where no relative comparisons were possible. In total, 97 participants viewed simple line drawings with high or low visual clarity, presented at four different presentation durations, and rated for felt fluency, liking, and certainty. Our results show that the manipulation of visual clarity led to differences in felt fluency and certainty regardless of being manipulated within- or between-participants. However, liking ratings were only affected when ease-of-processing was manipulated within-participants. Thus, feelings of fluency do not depend on the nature of the reference. On the other hand, participants liked fluent stimuli more only when there were other stimuli varying in ease-of-processing. Thus, relative differences in fluency seem to be crucial for liking judgments.     

Molecular beacon sequence design algorithm

A method based on Web-based tools is presented to design optimally functioning molecular beacons. Molecular beacons, fluorogenic hybridization probes, are a powerful tool for the rapid and specific detection of a particular nucleic acid sequence. However, their synthesis costs can be considerable. Since molecular beacon performance is based on its sequence, it is imperative to rationally design an optimal sequence before synthesis. The algorithm presented here uses simple Microsoft Excel formulas and macros to rank candidate sequences. This analysis is carried out using mfold structural predictions along with other free Web-based tools. For smaller laboratories where molecular beacons are not the focus of research, the public domain algorithm described here may be usefully employed to aid in molecular beacon design.     

ESCHERICHIA COLI Gene Induction by Alkylation Treatment

Searches for alkylation-inducible (aid) genes of Escherichia coli have been conducted by screening random fusions of the Mu-dl(ApR lac) phage for fusions showing increased beta-galactosidase activity after treatment with methylating agents, but not after treatments with UV-irradiation. In this report we describe gene fusions that are specifically induced by alkylation treatments. Nine new mutants are described, and their properties are compared with the five mutants described previously. The total of 14 fusion mutants map at five distinct genetic loci. They can be further subdivided on the basis of their induction by methyl methanesulfonate (MMS) and N-methyl-N' -nitro-N-nitrosoguanidine (MNNG). alkA, aidB and aidD are induced by both agents and appear to be regulated by ada. Neither aidC nor aidI is regulated by ada. Moreover, since aidC is induced only by MNNG and aidI is induced only by MMS, these two genes are likely to be individually regulated. Thus, there appear to be at least three different regulatory mechanisms controlling aid genes.     

New observations on the fine structure of Chrysochromulina strobilus Parke and Manton with special reference to some unusual features of the haptonema and scales

Summary A new isolate of C. strobilus Parke and Manton has been investigated with light and electron microscopy to add significant details not previously studied. With the aid of a ciné record, to be described more fully elsewhere, some of the more important haptonema movements have been accurately timed. With the aid of improved technical methods of electron microscopy, new observations have been made on the haptonema base, and on the structure and mode of origin of the scales. The presence of 6 microtubules (instead of the more usual 7) in the very long haptonema of this species has been confirmed but the elaborate changes in tubule number and arrangement which take place in the haptonema base are shown to be essentially like those of other species. The morphology and arrangement of the two types of scale present on the cell are as previously described though information on several new and taxonomically valuable surface features have been added. The cup-shaped scales in particular are shown to be more different from those of other species now known in the genus than might previously have been recognised. This difference extends to the position of nascent scales within the Golgi system which is described in a preliminary way. Further discussion is deferred until some other new isolates representing related taxa have been described and named.     

西藏申扎地区奥陶纪鹦鹉螺类化石的新材料

塔尔玛桥东-扎扛一带是近年发现的藏北地区第二个有可靠生物化石依据的奥陶系出露区。描述的鹦鹉螺化石是该区鹦鹉螺化石的一小部分,包括1新属、2新种和1未定种,分别是Taermaocerasgen.nov.,Taer-maocerasregularegen.etsp.nov.,Taermaocerasovatumgen.etsp.nov.及Taermaocearssp.。     

Use of hydrophobic moment plot methodology to aid the identification of oblique orientated alpha-helices

A number of alpha-helix forming peptides have been reported which appear to promote membrane fusion and other biological events related to the disruption of a hydrophobic/hydrophilic interface, due to the presence of a hydrophobicity gradient along the helical long axis. When alpha-helices from this class were analysed according to hydrophobic moment plot methodology a linear association was found to exist between the mean hydrophobic moment, , and the corresponding mean hydrophobicity, . This association was described by the least squares regression line: =0.508-0.422 and, here, a methodology to aid the prediction of oblique orientated alpha-helices is presented, based on a 99% prediction band around this regression line. This methodology is intended to provide an initial identification of candidates for further investigation by other techniques such as the molecular hydrophobic potential and laboratory based experimentation, not to assign function.     

Using a mock trial to make a difficult clinical decision.

Many clinical decisions have to be taken with inadequate scientific information. Reaching a consensus among experts has been tried as one response to this problem. Another, described here, is to use legal process to dissect a difficult question. In this case a mock trial--using barristers, expert witnesses, and a jury--was conducted on whether bone marrow transplantation should be offered to all children with symptomatic sickle cell disease. Transplantation seems to offer about a 90% cure rate for a condition that may kill 15% of children before they reach 20. But transplantation carries a 10% risk of death or severe disability, and doctors cannot predict which children will suffer severely from their sickle cell disease and which will suffer little or nothing. The jury eventually reached a majority decision that transplantation should not be offered now to all symptomatic children.     

Potential of Olfactory Ensheathing Cells from Different Sources for Spinal Cord Repair

Spinal cord injury (SCI) induces a permanent disability in patients. To this day no curative treatment can be proposed to restore lost functions. Therefore, extensive experimental studies have been conducted to induce recovery after SCI. One of the most promising therapies is based on the use of olfactory ensheathing cells (OECs). OECs can be obtained from either the olfactory bulbs (OB-OECs) or from olfactory mucosa (OM-OECs), involving a less invasive approach for autotransplantation. However the vast majority of experimental transplantations have been focusing on OB-OECs although the OM represents a more accessible source of OECs. Importantly, the ability of OM-OECs in comparison to OB-OECs to induce spinal cord recovery in the same lesion paradigm has never been described. We here present data using a multiparametric approach, based on electrophysiological, behavioral, histological and magnetic resonance imaging experiments on the repair potential of OB-OECs and OM-OECs from either primary or purified cultures after a severe model of SCI. Our data demonstrate that transplantation of OECs obtained from OB or OM induces electrophysiological and functional recovery, reduces astrocyte reactivity and glial scar formation and improves axonal regrowth. We also show that the purification step is essential for OM-OECs while not required for OB-OECs. Altogether, our study strongly indicates that transplantation of OECs from OM represents the best benefit/risk ratio according to the safety of access of OM and the results induced by transplantations of OM-OECs. Indeed, purified OM-OECs in addition to induce recovery can integrate and survive up to 60 days into the spinal cord. Therefore, our results provide strong support for these cells as a viable therapy for SCI.     

Localization of one gene for tuberous sclerosis within 9q32-9q34, and further evidence for heterogeneity.

Tuberous sclerosis (TSC) is an autosomal dominant disorder with both neurological and cutaneous manifestations often resulting in significant disability. Although it has been studied clinically and biochemically for many years, the underlying pathophysiology remains unknown. Genetic linkage analysis provides an alternative strategy for understanding the genetic etiology of this disease. Genetic linkage of a gene for TSC to loci in 9q32-9q34 has been reported but has not been a universal finding, since absence of linkage to 9q loci, as well as linkage to loci on 11q, have also been reported. We present here data on 22 families (21 previously unreported) segregating TSC. Our results strongly support a TSC locus in the 9q32-34 region for approximately one-third of families and provide significant evidence for genetic heterogeneity. Application of newly described highly polymorphic dinucleotide repeat marker loci in TSC greatly enhanced the informativeness of our pedigrees and was vital for detecting the heterogeneity. No clear evidence of linkage to chromosome 11q22 markers was found, suggesting that a still unidentified TSC locus elsewhere in the genome may account for the majority of TSC families.     

Morphology and molecular phylogeny of Pseudotrichonympha hertwigi and Pseudotrichonympha paulistana (Trichonymphea, parabasalia) from neotropical rhinotermitids

Pseudotrichonympha is a large hypermastigote parabasalian found in the hindgut of several species of rhinotermitid termites. The genus was discovered more than 100 years ago, and although over a dozen species have since been described, this represents only a small fraction of its likely diversity: the termite genera from which Pseudotrichonympha is known are all species rich, and in most cases their hindgut symbionts have not been examined. Even formally described species are mostly lacking in detailed microscopic data and/or sequence data. Using small subunit ribosomal RNA gene sequences and light and scanning electron microscopy we describe here the morphology and molecular phylogenetic position of two Pseudotrichonympha species: the type species for the genus, Pseudotrichonympha hertwigi from Coptotermes testaceus (described previously in line drawing only), and Pseudotrichonympha paulistana from Heterotermes tenuis (described previously based on light microscopy only).     

The effect of elastase on chickens with endogenous hyperlipidemia

Elastase has been reported to have a multiplicity of activities which may be protective against atherosclerosis. The data reported here support those reports and show a clear antiatherosclerotic effect in hyperlipidemic chickens. We have shown here that a reduction in calcium and lipid accumulation in aortic tissue and possibly a plasma cholesterol lowering effect can be seen in the chicken when treated with elastase. The most important effect in this animal is probably to aid removal of lipid bound to elastin in the intima. This was achieved at a dose of only 600 U elastase while reductions in tissue calcium required 1800 U elastase.     

The human faecal flora and Crohn’s disease

The aetiology of Crohn’s disease (CD), a chronic inflammatory disease of the intestines, is not known but a genetic predisposition to CD has been well demonstrated. Studies on the isolation of bacteria from tissues and the faecal flora from CD patients are reviewed and their results compared with those from our laboratory. Serum antibodies against a variety of bacteria have been described but none has been found to be specific for CD. In our laboratory, higher numbers of coccoid anaerobes have been found in the faecal flora of CD patients. The use of agglutination reactions with four coccoid anaerobes as a diagnostic aid for CD is reviewed. No evidence has been found, however, for a primary role of the agglutinating antibodies in the pathogenesis of CD. On the other hand, one of the coccoid strains has been found to have several characteristics suggesting a role in CD, such as activation of the alternative pathway of complement, the failure of opsonization by specific IgG antibody and the binding of (non-specific) IgG onto the bacteria by the Fc portion. The composition of the faecal flora has been found to depend on genetic characteristics of the host. It is suggested that the genetic predisposition to CD is based on the genetically determined indigenous faecal flora present.     

Auditory evoked potentials for the assessment of depth of anaesthesia: different configurations of artefact detection algorithms.

Monitoring the depth of anaesthesia has become an important research topic in the field of biosignal processing. Auditory evoked potentials (AEPs) have been shown to be a promising tool for this purpose. Signals recorded in the noisy environment of an operating theatre are often contaminated by artefacts. Thus, artefact detection and elimination in the underlying electroencephalogram (EEG) are mandatory before AEP extraction. Determination of a suitable artefact detection configuration based on EEG data from a clinical study is described. Artefact detection algorithms and an AEP extraction procedure encompassing the artefact detection results are presented. Different configurations of artefact detection algorithms are evaluated using an AEP verification procedure and support vector machines to determine a suitable configuration for the assessment of depth of anaesthesia using AEPs.     

Fingerspelling as a Novel Gateway into Reading Fluency in Deaf Bilinguals

Studies have shown that American Sign Language (ASL) fluency has a positive impact on deaf individuals’ English reading, but the cognitive and cross-linguistic mechanisms permitting the mapping of a visual-manual language onto a sound-based language have yet to be elucidated. Fingerspelling, which represents English orthography with 26 distinct hand configurations, is an integral part of ASL and has been suggested to provide deaf bilinguals with important cross-linguistic links between sign language and orthography. Using a hierarchical multiple regression analysis, this study examined the relationship of age of ASL exposure, ASL fluency, and fingerspelling skill on reading fluency in deaf college-age bilinguals. After controlling for ASL fluency, fingerspelling skill significantly predicted reading fluency, revealing for the first-time that fingerspelling, above and beyond ASL skills, contributes to reading fluency in deaf bilinguals. We suggest that both fingerspelling—in the visual-manual modality—and reading—in the visual-orthographic modality—are mutually facilitating because they share common underlying cognitive capacities of word decoding accuracy and automaticity of word recognition. The findings provide support for the hypothesis that the development of English reading proficiency may be facilitated through strengthening of the relationship among fingerspelling, sign language, and orthographic decoding en route to reading mastery, and may also reveal optimal approaches for reading instruction for deaf and hard of hearing children.