The evolving ribosome: from non-coded peptide bond formation to sophisticated translation machinery

Structural analysis supported by biochemical, mutagenesis and computational evidence, revealed that the contemporary ribosome's active site is a universal symmetrical pocket made of ribosomal RNA. This pocket seems to be the remnant of the proto-ribosome, a dimeric RNA assembly evolved by gene duplication, capable of autonomously catalyzing peptide bond formation and non-coded amino acid polymerization.     

OT promotes closer interpersonal distance among highly empathic individuals

The space between people, or ‘interpersonal distance’, creates and defines the dynamics of social interactions and is a salient cue signaling responsiveness and feeling comfortable. This distance is implicit yet clearly felt, especially if someone stands closer or farther away than expected. Increasing evidence suggests that Oxytocin (OT) serves as a social hormone in humans, and that one of its roles may be to alter the perceptual salience of social cues. Considering that empathic ability may shape the way individuals process social stimuli, we predicted that OT will differentially affect preferred interpersonal distance depending on individual differences in empathy. Participants took part in two interpersonal distance experiments: In the first, they had to stop a (computer visualized) protagonist when feeling most comfortable; in the second, they were asked to choose the room in which they would later discuss intimate topics with another. Both experiments revealed an interaction between the effect of OT and empathy level. Among highly empathic individuals, OT promoted the choice of closer interpersonal distances. Yet, OT had an opposite effect on individuals with low empathic traits. We conclude that the enhancement of social cues following OT administration may have opposite effects on individuals with different empathic abilities.     

Ashkenazi Parkinson’s disease patients with the LRRK2 G2019S mutation share a common founder dating from the second to fifth centuries

The LRRK2 G2019S mutation is a major genetic determinant of Parkinson’s disease (PD) across the world that occurs at an elevated frequency in Ashkenazi Jews. We determined the LRRK2 haplotypes in 77 G2019S carriers, mostly Ashkenazi Jews, and in 50 noncarrier Ashkenazi PD patients, using 16 genetic markers. A single haplotype was detected in all mutation carriers, indicating that these individuals share a common founder. Using a maximum-likelihood method, we estimate that Ashkenazi Jews with G2019S share a common ancestor who lived ～1,830 (95% CI 1,560–2,160) years ago, around the second century, after the second Jewish Diaspora.     

Bullying perpetration and victimization associations to suicide behavior: a longitudinal study

Previous studies have reported a longitudinal association between cybervictimization and suicidal thoughts and behavior. However, the relationship between cyber-perpetration and prospective suicide risk remains unclear. The sample was composed of 2150 at-risk adolescents (mean age 15.42), enrolled in Vocational Education and Training high schools in Israel. Cyberbullying, traditional bullying, depression, hostility, serious suicidal ideations, and suicide attempts were assessed through self-report questionnaires at the beginning of the school year and one year later. All types of victimization and preparation were cross-sectionally associated with suicide ideation and attempts. Longitudinal associations were found between cyber-perpetration and suicidal ideation/attempts. Cyber-perpetrators were found to be over twice more likely to report serious suicidal ideation (OR = 2.04) or attempt suicide (OR = 2.64) in the subsequent year compared to noninvolved adolescents. These associations were significant even after adjusting for baseline depression, hostility, and traditional bullying. Traditional bullying perpetration was prospectively associated with suicide attempts. Traditional victimization was cross-sectionally associated with suicide ideation and attempts but not prospectively. Cybervictimization was prospectively associated with suicide ideation but not to suicide attempts. The findings demonstrate the prospective risk of involvement in bullying in regard to suicide ideation and behavior. Cyberbullying was found to be a somewhat differentiated phenomena from traditional bullying.

     

Dorsal Raphe Dopamine Neurons Signal Motivational Salience Dependent on Internal State,Expectation, and Behavioral Context

The ability to recognize motivationally salient events and adaptively respond to them is critical for survival. Here, we tested whether dopamine (DA) neurons in the dorsal raphe nucleus (DRN) contribute to this process in both male and female mice. Population recordings of DRN^DA neurons during associative learning tasks showed that their activity dynamically tracks the motivational salience, developing excitation to both reward-paired and shock-paired cues. The DRN^DA response to reward-predicting cues was diminished after satiety, suggesting modulation by internal states. DRN^DA activity was also greater for unexpected outcomes than for expected outcomes. Two-photon imaging of DRN^DA neurons demonstrated that the majority of individual neurons developed activation to reward-predicting cues and reward but not to shock-predicting cues, which was surprising and qualitatively distinct from the population results. Performing the same fear learning procedures in freely-moving and head-fixed groups revealed that head-fixation itself abolished the neural response to aversive cues, indicating its modulation by behavioral context. Overall, these results suggest that DRN^DA neurons encode motivational salience, dependent on internal and external factors.SIGNIFICANCE STATEMENT Dopamine (DA) contributes to motivational control, composed of at least two functional cell types, one signaling for motivational value and another for motivational salience. Here, we demonstrate that DA neurons in the dorsal raphe nucleus (DRN) encode the motivational salience in associative learning tasks. Neural responses were dynamic and modulated by the animal''s internal state. The majority of single-cells developed responses to reward or paired cues, but not to shock-predicting cues. Additional experiments with freely-moving and head-fixed mice showed that head-fixation abolished the development of cue responses during fear learning. This work provides further characterization on the functional roles of overlooked DRN^DA populations and an example that neural responses can be altered by head-fixation, which is commonly used in neuroscience.     

The different faces of Creutzfeldt-Jacob Disease CJD in psychiatry

Objective

Creutzfeldt-Jacob Disease (CJD) is a rapidly progressive spongiform disease of the central nervous system. Psychiatric symptoms, though considered rare, can be the presenting symptoms of CJD and impose diagnosis difficulties. We reviewed prospectively our database to identify the frequency of psychiatric symptoms as identifying symptoms among our community.

Methods

We included all patients in Sheba Medical Center who were diagnosed with CJD between the years 2006 and 2012. Data were collected retrospectively.

Results

Twenty-three patients with CJD were admitted to our hospital during this 6-year period. Among them, 10 (44%) were diagnosed first as “psychiatric patients” due to psychiatric presenting symptoms.

Conclusion

In our series, the frequency of misleading psychiatric symptom was 44%. Clinicians should therefore include CJD in their differential diagnoses of new onset dementia, particularly when associated psychosis and depression symptoms persist and worsen, despite standard psychiatric treatments.     

Fall risk and gait in Parkinson's disease: The role of the LRRK2 G2019S mutation

Patients with Parkinson's disease (PD) who carry the G2019S mutation (a glycine to serine substitution at amino acid 2019) in the leucine‐rich repeat kinase 2 (LRRK2) gene are generally believed to be clinically indistinguishable from patients with sporadic PD. There are, however, conflicting reports on the relationship between the mutation and the motor phenotype. We quantitatively compared gait and mobility in patients with PD carriers of the G2019S mutation to non‐carrier patients with PD to better understand the genotype‐phenotype relationship. Fifty patients with PD carriers of the G2019S LRRK2 mutation and 50 age, disease duration, and disease severity matched PD non‐carriers were studied. An accelerometer quantified gait under three walking conditions: usual‐walking, dual‐tasking, and fast‐walking. The Unified Parkinson's Disease Rating Scale classified patients into PD sub‐types and the Timed Up and Go quantified mobility and fall risk. In all three walking conditions, gait variability was larger and the walking pattern was less consistent among the PD mutation carriers (P < 0.016). The PD carriers also took longer to complete the Timed Up and Go (P = 0.011) and were more likely to report having fallen in the previous year (P = 0.018). 64% of the PD carriers were classified as belonging to the postural‐instability‐gait‐difficulty (PIGD) sub‐type compared to only 17% of the PD non‐carriers (P < 0.0001). Among patients with PD, the G2019S mutation in the LRRK2 gene is apparently associated with increased gait variability, an increased fall risk, and the PIGD sub‐type. Therapeutic approach specifically designed to delay gait disturbances and falls may be justified in patients who carry the G2019S mutation. © 2013 International Parkinson and Movement Disorder Society     

Bone strength in multiple sclerosis: cortical midtibial speed-of-sound assessment

It has been previously suggested that multiple sclerosis (MS) patients are at increased risk for osteoporosis due to reduced mobility, decreased exposure to sunlight and recurrent steroid treatment. In order to systematically evaluate bone strength we assessed 256 MS patients (171 females, 75 males) through quantitative ultrasound measurement of cortical bone. Tibial speed of sound (SOS, m/sec) was measured at midpoint of the tibial shaft using a Soundscan 2000 (Myriad Ultrasound Systems, Rehovot, Israel) and results were compared to age- and gender-matched population norms. T-score distribution in male MS patients was similar to normal population. In contrast, for female MS patients T-score distribution was significantly different from population norms, reflected by increased SOS in 30.4% (T-score intervals 1-2 and >2 above normal values; P=0.001), compared with 7.4% in controls. These findings held true for both female patients younger and older than 45 years of age. Increased neurological disability and specifically motor involvement were more frequent in female patients with increased SOS (P<0.05). Bone strength was preserved in MS patients. In a subgroup of female patients increased SOS was conceivably related to spasticity.     

Effect of a niobium-containing titanium alloy on osteoblast behavior in culture

Background: The chemistry of titanium is a key factor in determining implant–tissue interactions. Reports that a vanadium-based titanium alloy (Ti–6Al–4V) exhibits some cytotoxicity led to a search for an alternative.
Aim: The aim of the present study was to investigate the behavior of human osteoblast-like cells (Saos-2) cultured on Ti–6Al–4V or Ti–6Al–7Nb disks with a rough or a machined surface.
Results: In all four groups, the cells proliferated rapidly between days 1 and 3, and then plateaued. On day 1 of culture, the highest proliferation rate was of cells cultured on disks containing Nb with a machined surface. On day 7, there was no significant difference in cell density on all the tested surfaces. Alkaline phosphatase (ALP) activity was lower on the machined surfaces, regardless of the material used, suggesting that cells on rough surfaces exhibit a more mature phenotype. On day 3, cells cultured on rough disks made of Ti–6Al–7Nb showed the highest ALP activity; the lowest activity was observed on the machined Ti–6Al–4V surface. The highest level of osteocalcin (day 7) was found in the cells cultured on rough Ti–6Al–7Nb disks. Also, higher levels of transforming growth factor (TGFβ) were noted for cells cultured on the rough Ti–6Al–7Nb disks, suggesting that the Nb-containing alloy supports more rapid maturation of the osteoblast.
Conclusions: The results of the present study suggest that according to our cell culture preclinical model, Ti–6Al–7Nb may replace the Ti–6Al–4V alloy as an implant material.