A cellular correlate of learning-induced metaplasticity in the hippocampus

Metaplasticity, the plasticity of synaptic plasticity, is thought to have a pivotal role in activity-dependent modulation of synaptic connectivity, which underlies learning and memory. Metaplasticity is usually attributed to modifications in glutamate receptor-mediated synaptic transmission. However, experimental evidence and theoretical considerations suggest that learning reduces the predisposition for further synaptic strengthening, while behavioral studies show that learning capability is enhanced by prior learning. Here we show that enhanced neuronal excitability in CA1 pyramidal neurons, but not enhanced synaptic transmission, occurs prior to rule learning of an olfactory discrimination task. This transient enhancement lasts for 1 day after rule learning, is apparent throughout the cell population and results from reduction in the medium and slow after-hyperpolarizations that control spike frequency adaptation. Such olfactory learning-induced increased excitability in hippocampal neurons enhances the rats' learning capability in another hippocampus-dependent task, the Morris water maze. Once olfactory discrimination rule learning is acquired, its maintenance is not dependent on the reduced post-burst AHP in hippocampal neurons. However, the enhanced spatial learning capability of olfactory-trained rats in the water maze is diminished once the post burst AHP in CA1 pyramidal cells resumes its initial value. We suggest that enhanced excitability of CA1 neurons may serve as a mechanism for generalized enhancement of hippocampus-dependent learning capability. In the presence of such enhanced neuronal excitability, the hippocampal network enters into a 'learning mode' in which a variety of hippocampus-dependent skills are acquired rapidly and efficiently.     

Recto-vaginal/urethral fistula: repair with gracilis muscle transposition

This study was designed to assess the efficacy of gracilis muscle transposition in repairing recto-vaginal and rectourethral fistula. All patients had fecal diversion as a preliminary or concurrent step to fistula repair. Success was defined as healed fistula after stoma closure. Results: Six females and four males underwent gracilis muscle transposition from 1999 to 2006. Gracilis muscle transposition is a viable option for repairing fistulas between the urethra, vagina and the rectum, especially after failed perineal or trans-anal repair. It is associated with low morbidity and good success rate. Underlying Crohn's disease and previous radiation are associated with poor prognosis.     

Proteolytic activation of the SARS-coronavirus spike protein: Cutting enzymes at the cutting edge of antiviral research

The severe acute respiratory syndrome (SARS) pandemic revealed that zoonotic transmission of animal coronaviruses (CoV) to humans poses a significant threat to public health and warrants surveillance and the development of countermeasures. The activity of host cell proteases, which cleave and activate the SARS-CoV spike (S) protein, is essential for viral infectivity and constitutes a target for intervention. However, the identities of the proteases involved have been unclear. Pioneer studies identified cathepsins and type II transmembrane serine proteases as cellular activators of SARS-CoV and demonstrated that several emerging viruses might exploit these enzymes to promote their spread. Here, we will review the proteolytic systems hijacked by SARS-CoV for S protein activation, we will discuss their contribution to viral spread in the host and we will outline antiviral strategies targeting these enzymes. This paper forms part of a series of invited articles in Antiviral Research on “From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.’’     

Classification of cries of infants with cleft-palate using parallel hidden Markov models

This paper addresses the problem of classification of infants with cleft palate. A hidden Markov model (HMM)-based cry classification algorithm is presented. A parallel HMM (PHMM) for coping with age masking, based on a maximum-likelihood decision rule, is introduced. The performance of the proposed algorithm under different model parameters and different feature sets is studied using a database of cries of infants with cleft palate (CLP). The proposed algorithm yields an average of 91% correct classification rate in a subject- and age-dependent experiment. In addition, it is shown that the PHMM significantly outperforms the HMM performance in classification of cries of CLP infants of different ages.     

Differentiating between heat pain intensities: the combined effect of multiple autonomic parameters

Although it is well known that pain induces changes in autonomic parameters, the extent to which these changes correlate with the experience of pain is under debate. The aim of the present study was to compare a combination of multiple autonomic parameters and each parameter alone in their ability to differentiate among 4 categories of pain intensity. Tonic heat stimuli (1minute) were individually adjusted to induce no pain, low, medium, and high pain in 45 healthy volunteers. Electrocardiogram, photoplethysmogram, and galvanic skin response were recorded, and the following parameters were calculated: heart rate; heart rate variability-high frequency (0.15 to 0.4Hz) spectral power; skin conductance level; number of skin conduction fluctuations; and photoplethysmographic pulse wave amplitude. A combination of parameters was created by fitting an ordinal cumulative logit model to the data and using linear coefficients of the model. Friedman test with post-hoc Wilcoxon test were used to compare between pain intensity categories for every parameter alone and for their linear combination. All of the parameters successfully differentiated between no pain and all other pain categories. However, none of the parameters differentiated between all 3 pain categories (i.e., low and medium; medium and high; low and high). In contrast, the linear combination of parameters significantly differentiated not only between pain and no pain, but also between all pain categories (P<.001 to .02). These results suggest that multiparameter approaches should be further investigated to make progress toward reliable autonomic-based pain assessment.     

In vitro assembly of physiological cohesin/DNA complexes

Cohesin is a member of the Smc family of protein complexes that mediates higher-order chromosome structure by tethering different regions of chromatin. We present a new in vitro system that assembles cohesin-DNA complexes with in vivo properties. The assembly of these physiological salt-resistant complexes requires the cohesin holo-complex, its ability to bind ATP, the cohesin loader Scc2p and a closed DNA topology. Both the number of cohesin molecules bound to the DNA substrate and their distribution on the DNA substrate are limited. Cohesin and Scc2p bind preferentially to cohesin associated regions (CARs), DNA sequences with enriched cohesin binding in vivo. A subsequence of CARC1 promotes cohesin binding to neighboring sequences within CARC1. The enhancer-like function of this sequence is validated by in vivo deletion analysis. By demonstrating the physiological relevance of these in vitro assembled cohesin-DNA complexes, we establish our in vitro system as a powerful tool to elucidate the mechanism of cohesin and other Smc complexes.     

Students with visual impairments in Israel: quality of life as a subjective experience

The present paper is based on research that investigated the quality of life of students with visual impairments, included in the regular education system, according to their own perceptions as reported in individual open interviews. The research comprised 19 students between the ages of 14 and 19 years. The main findings revealed three major themes: life in school with a focus on teachers' behavior towards the pupil; peers' reactions and the impact of stigma; family coping with the disability. Mixed feelings appeared in the first two themes. Regarding their teachers, the students reported support while at the same time they also felt a lack of sincere respect. Concerning peers, students felt that stigma affected their friendship behavior. Finally, most reports indicated satisfaction with the family bonds. Yet, there is almost no direct reference to the visual problem.