Negative transcriptional feedback loops are a core feature of eukaryotic circadian clocks and are based on rhythmic interactions between clock-specific repressors and transcription factors. In Drosophila , the repression of dCLOCK (dCLK)-CYCLE (CYC) transcriptional activity by dPERIOD (dPER) is critical for driving circadian gene expression. Although growing lines of evidence indicate that circadian repressors such as dPER function, at least partly, as molecular bridges that facilitate timely interactions between other regulatory factors and core clock transcription factors, how dPER interacts with dCLK-CYC to promote repression is not known. Here, we identified a small conserved region on dPER required for binding to dCLK, termed CBD (for dCLK binding domain). In the absence of the CBD, dPER is unable to stably associate with dCLK and inhibit the transcriptional activity of dCLK-CYC in a simplified cell culture system. CBD is situated in close proximity to a region that interacts with other regulatory fac...

Since 2004, herbal mixtures broadly known as Spice/K2, containing synthetic cannabinoids (SC) such as JWH-018, have been marketed as a legal marijuana surrogate. Previous studies of our group showed that JWH-018 has CB1-receptor dependent reinforcing pr...

The attentional system (AttS) is important for the survival and behavioral performance of the species. Cannabinoids have become a research interest in light of possible adverse effects that the use of marijuana can have. These substances bind to CB1 and...

Indoleamine 2,3-dioxygenases (Ido1 and Ido2) are the first and rate-limiting enzymes for the conversion of tryptophan to kynurenine (Kyn). Kyn production, following Ido1/2 upregulation in response to inflammatory signals, promotes immunosuppression. Add...

The neurotransmitter dopamine (DA) plays a central role in the regulation of learning, memory, emotion, cognition and locomotion. Aberrant dopaminergic signaling is associated with a variety of neurological and neuropsychiatric pathologies, including Pa...

We investigated isoform composition of aggregated tau in the brains of Pick’s disease (PiD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), argyrophilic grain disease (AGD) and ‘senile dementia of the tangle type (SDT)’ by immunoblot analysis of sarkosyl-insoluble fractions of brain homogenates. We also examined the adjacent brain tissues immunohistochemically with a rabbit antibody, Ex10, which specifically recognizes exon 10 of tau. The Ex10 recognizes tau isoforms with four microtubule-binding repeats (4Rtau) but not those with three microtubule-binding repeats (3Rtau). Sarkosyl-insoluble tau from the brains of patients with CBD and PSP consisted of 4Rtau. Insoluble tau from the brains of PiD, AGD, and SDT contained both 3Rtau and 4Rtau, where 3Rtau predominated over 4Rtau in PiD brains. In brain tissues of CBD and PSP, Ex10 immunostained all neuronal and glial structures such as pre-tangles, astrocytic plaques and oligodendroglial coiled bodies. In the PiD brains, astrocytic inc...

Addiction to cocaine is commonly preceded by experiences with legal and decriminalized drugs, such as alcohol, nicotine and marijuana. The biological mechanisms by which these gateway drugs contribute to cocaine addiction are only beginning to be unders...

Autism spectrum disorder (ASD) is a group of neuro-developmental disabilities which are characterized by impairments in communication, social interaction, behavioral control, and emotional instability. In Israel, individual with ASD with sever aggressiv...

Objective: To objectively quantify neuropathological white matter (WM) burden in relation to grey matter (GM) in frontotemporal lobar degeneration (FTLD) subtypes. Background: Antemortem distinction of FTLD proteinopathies, including tauopathies (FTLD-T...

In terrestrial locomotion, sensory feedback from load sensors is important for altering ongoing motor output on a step-by-step basis. We investigated the influence of load signals from the leg on motoneuron pools of the thorax-coxa (ThC) joint in the stick insect walking system. Load sensors were stimulated during rhythmic, alternating activity in protractor coxae (ProCx) and retractor coxae (RetCx) motoneuron pools. Alternating activity in the segment of interest was induced by mechanical stimulation of the animal or pharmacological activation of the isolated thoracic ganglia. Load signals from the legs altered the timing of ThC motoneuron activity by resetting and entraining the activity of the central rhythm generating network of the ThC joint. In the front and middle legs, load signals induced or promoted RetCx activity and decreased or terminated ProCx activity. In the hindleg, reverse transitions were elicited, with increasing load terminating RetCx and initiating ProCx activity. Studies in semi-inta...