Hovering at a low altitiude

In the spring quarter of 1988 I became acquainted with computer graphics which opened up great visual possibilities for me. The computer enabled me to layer and integrate various photographic fragments of reality, and enhanced my ability to reveal aspects of my personality-- my fears, my desires, and my feeling of confusion between contrasting values within my life. I could now communicate on a more general level, dealing with not just personal but cultural issues such as the role of mythology in our everyday life and how we deal with all the information that we absorb in modern life

A prospective clinical cohort-based study of the prevalence of OCD, obsessive compulsive and related disorders, and tics in families of patients with OCD

Background: The lifetime prevalence of obsessive − compulsive disorder (OCD) is currently estimated at 2 − 3% and the prevalence in first-degree family members is estimated to range between 10 and 11%. Separating OCD from other anxiety disorders and including it into the new “obsessive − compulsive and related disorders” (OCRDs) category has had a dramatic impact on the diagnosis, while also contributing to the better understanding of the genetics of these disorders. Indeed, grouping OCD with body dysmorphic disorder (BDD), and body-focused repetitive behaviors such as trichotillomania (hair pulling), onychophagia (nail biting), and excoriation (skin picking) into the same diagnostic family has resulted in a much greater lifetime prevalence (> 9%). These diagnostic changes necessitate an updated epidemiological study, thus motivating this investigation. Methods: The study sample comprised of 457 patient’s cases from an Israeli and an Australian OCD center. Interviews were completed as a part of the intake or during treatment in each of the centers. Prevalence of OCD, OCRDs, tics, and other psychiatric comorbidities in first- and second-degree relatives was assessed by interviewing the OCD patients. Interviews were conducted by at least two researchers (LC, OBA, JZ) and only family information on which the interviewers have reached consensus was considered. Results: Initial analyses revealed an increase of OCD and OCRD prevalence in first- and second-degree family members as compared to the current literature due to reclassification of these disorders in DSM-5. Conclusion: The new category of OCRD has changed the landscape of epidemiological studies in OCD. Further and broader studies are needed in order to better understand the lifetime prevalence of OCRD in first- and second-degrees family member

Upregulation of Neurotrophic Factors Selectively in Frontal Cortex in Response to Olfactory Discrimination Learning

We have previously shown that olfactory discrimination learning is accompanied by several forms of long-term enhancement in synaptic connections between layer II pyramidal neurons selectively in the piriform cortex. This study sought to examine whether the previously demonstrated olfactory-learning-task-induced modifications are preceded by suitable changes in the expression of mRNA for neurotrophic factors and in which brain areas this occurs. Rats were trained to discriminate positive cues in pair of odors for a water reward. The relationship between the learning task and local levels of mRNA for brain-derived neurotrophic factor, tyrosine kinase B, nerve growth factor, and neurotrophin-3 in the frontal cortex, hippocampal subregions, and other regions were assessed 24 hours post olfactory learning. The olfactory discrimination learning activated production of endogenous neurotrophic factors and induced their signal transduction in the frontal cortex, but not in other brain areas. These findings suggest that different brain areas may be preferentially involved in different learning/memory tasks

PAR Genes: Molecular Probes to Pathological Assessment in Breast Cancer Progression

Taking the issue of tumor categorization a step forward and establish molecular imprints to accompany histopathological assessment is a challenging task. This is important since often patients with similar clinical and pathological tumors may respond differently to a given treatment. Protease-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR), is the first member of the mammalian PAR family consisting of four genes. PAR1 and PAR2 play a central role in breast cancer. The release of N-terminal peptides during activation and the exposure of a cryptic internal ligand in PARs, endow these receptors with the opportunity to serve as a “mirror-image” index reflecting the level of cell surface PAR1&2-in body fluids. It is possible to use the levels of PAR-released peptide in patients and accordingly determine the choice of treatment. We have both identified PAR1 C-tail as a scaffold site for the immobilization of signaling partners, and the critical minimal binding site. This binding region may be used for future therapeutic modalities in breast cancer, since abrogation of the binding inhibits PAR1 induced breast cancer. Altogether, both PAR1 and PAR2 may serve as molecular probes for breast cancer diagnosis and valuable targets for therapy

Text mining for biology - the way forward: opinions from leading scientists

This article collects opinions from leading scientists about how text mining can provide better access to the biological literature, how the scientific community can help with this process, what the next steps are, and what role future BioCreative evaluations can play. The responses identify several broad themes, including the possibility of fusing literature and biological databases through text mining; the need for user interfaces tailored to different classes of users and supporting community-based annotation; the importance of scaling text mining technology and inserting it into larger workflows; and suggestions for additional challenge evaluations, new applications, and additional resources needed to make progress

Molecular imaging of cell death in vivo by a novel small molecule probe

Apoptosis has a role in many medical disorders, therefore assessment of apoptosis in vivo can be highly useful for diagnosis, follow-up and evaluation of treatment efficacy. ApoSense is a novel technology, comprising low molecular-weight probes, specifically designed for imaging of cell death in vivo. In the current study we present targeting and imaging of cell death both in vitro and in vivo, utilizing NST-732, a member of the ApoSense family, comprising a fluorophore and a fluorine atom, for both fluorescent and future positron emission tomography (PET) studies using an 18F label, respectively. In vitro, NST-732 manifested selective and rapid accumulation within various cell types undergoing apoptosis. Its uptake was blocked by caspase inhibition, and occurred from the early stages of the apoptotic process, in parallel to binding of Annexin-V, caspase activation and alterations in mitochondrial membrane potential. In vivo, NST-732 manifested selective uptake into cells undergoing cell-death in several clinically-relevant models in rodents: (i) Cell-death induced in lymphoma by irradiation; (ii) Renal ischemia/reperfusion; (iii) Cerebral stroke. Uptake of NST-732 was well-correlated with histopathological assessment of cell-death. NST-732 therefore represents a novel class of small-molecule detectors of apoptosis, with potential useful applications in imaging of the cell death process both in vitro and in vivo

UDP-N-Acetylglucosamine 2-Epimerase/N-Acetylmannosamine Kinase (GNE) Binds to Alpha-Actinin 1: Novel Pathways in Skeletal Muscle?

Hereditary inclusion body myopathy (HIBM) is a rare neuromuscular disorder caused by mutations in GNE, the key enzyme in the biosynthetic pathway of sialic acid. While the mechanism leading from GNE mutations to the HIBM phenotype is not yet understood, we searched for proteins potentially interacting with GNE, which could give some insights about novel putative biological functions of GNE in muscle. We used a Surface Plasmon Resonance (SPR)-Biosensor based assay to search for potential GNE interactors in anion exchanged fractions of human skeletal muscle primary culture cell lysate. Analysis of the positive fractions by in vitro binding assay revealed alpha-actinin 1 as a potential interactor of GNE. The direct interaction of the two proteins was assessed in vitro by SPR-Biosensor based kinetics analysis and in a cellular environment by a co-immunoprecipitation assay in GNE overexpressing 293T cells. Furthermore, immunohistochemistry on stretched mouse muscle suggest that both GNE and alpha-actinin 1 localize to an overlapping but not identical region of the myofibrillar apparatus centered on the Z line. The interaction of GNE with alpha-actinin 1 might point to its involvement in alpha-actinin mediated processes. In addition these studies illustrate for the first time the expression of the non-muscle form of alpha-actinin, alpha-actinin 1, in mature skeletal muscle tissue, opening novel avenues for its specific function in the sarcomere. Although no significant difference could be detected in the binding kinetics of alpha-actinin 1 with either wild type or mutant GNE in our SPR biosensor based analysis, further investigation is needed to determine whether and how the interaction of GNE with alpha-actinin 1 in skeletal muscle is relevant to the putative muscle-specific function of alpha-actinin 1, and to the muscle-restricted pathology of HIBM