A Perspective on the Potential Role of Neuroscience in the Court

This Article presents some lessons learned while offering expert testimony on neuroscience in courts. As a biomedical investigator participating in cutting-edge research with clinical and mentoring responsibilities, Dr. Ruben Gur, Ph.D., became involved in court proceedings rather late in his career. Based on the success of Dr. Gur and other research investigators of his generation, who developed and validated advanced methods for linking brain structure and function to behavior, neuroscience findings and procedures became relevant to multiple legal issues, especially related to culpability and mitigation. Dr. Gur found himself being asked to opine in cases where he could contribute expertise on neuropsychological testing and structural and functional neuroimaging. Most of his medical-legal consulting experience has been in capital cases because of the elevated legal requirement for thorough mitigation investigations in such cases, and his limited availability due to his busy schedule as a full-time professor and research investigator who runs the Brain and Behavior Lab at the University of Pennsylvania (“Penn”). Courtroom testimony, however, has not been a topic of his research and so he has not published extensively on the issues in peer-reviewed literature

Global Contagion of Non-Viral Information

Contagion in Online Social Networks (OSN) is typically measured by the tendency of users to re-post information or to adopt a new behavior after exposure to that information/behavior. Most contagion research is bound by modeling: (i) only local neighbor-to-neighbor contagion (ii) the spread of viral information. However, most contagion events are non-viral and can also occur globally by non-neighbors through for example, exposure to information by exploratory browsing, or by content recommendation algorithms. This study is the first to address the phenomenon of both global and local contagion of non-viral information in a quantitative way. Analysis of Twitter networks reveals the prevailing nature of global contagion, the different temporal patterns between global and local contagion, and the ways it varies across topical categories. An interesting finding shows that users who retweeted due to global contagion have more Followers than those who retweeted due to local contagion

Cytoplasmic anchorage of L-selectin controls leukocyte capture and rolling by increasing the mechanical stability of the selectin tether

L-selectin is a leukocyte lectin that mediates leukocyte capture and rolling in the vasculature. The cytoplasmic domain of L-selectin has been shown to regulate leukocyte rolling. In this study, the regulatory mechanisms by which this domain controls L-selectin adhesiveness were investigated. We report that an L-selectin mutant generated by truncation of the COOH-terminal 11 residues of L-selectin tail, which impairs association with the cytoskeletal protein α-actinin, could capture leukocytes to glycoprotein L-selectin ligands under physiological shear flow. However, the conversion of initial tethers into rolling was impaired by this partial tail truncation, and was completely abolished by a further four-residue truncation of the L-selectin tail. Physical anchorage of both cell-free tail-truncated mutants within a substrate fully rescued their adhesive deficiencies. Microkinetic analysis of full-length and truncated L-selectin–mediated rolling at millisecond temporal resolution suggests that the lifetime of unstressed L-selectin tethers is unaffected by cytoplasmic tail truncation. However, cytoskeletal anchorage of L-selectin stabilizes the selectin tether by reducing the sensitivity of its dissociation rate to increasing shear forces. Low force sensitivity (reactive compliance) of tether lifetime is crucial for selectins to mediate leukocyte rolling under physiological shear stresses. This is the first demonstration that reduced reactive compliance of L-selectin tethers is regulated by cytoskeletal anchorage, in addition to intrinsic mechanical properties of the selectin–carbohydrate bond

The incoherent feedforward loop can provide fold-change detection in gene regulation

Many sensory systems (e.g., vision and hearing) show a response that is proportional to the fold-change in the stimulus relative to the background, a feature related to Weber's Law. Recent experiments suggest such a fold-change detection feature in signaling systems in cells: a response that depends on the fold-change in the input signal, and not on its absolute level. It is therefore of interest to find molecular mechanisms of gene regulation that can provide such fold-change detection. Here, we demonstrate theoretically that fold-change detection can be generated by one of the most common network motifs in transcription networks, the incoherent feedforward loop (I1-FFL), in which an activator regulates both a gene and a repressor of the gene. The fold-change detection feature of the I1-FFL applies to the entire shape of the response, including its amplitude and duration, and is valid for a wide range of biochemical parameters

Profiling molecular and behavioral circadian rhythms in the non-symbiotic sea anemone Nematostella vectensis

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 5 (2015): 11418, doi:10.1038/srep11418.Endogenous circadian clocks are poorly understood within early-diverging animal lineages. We have characterized circadian behavioral patterns and identified potential components of the circadian clock in the starlet sea anemone, Nematostella vectensis: a model cnidarian which lacks algal symbionts. Using automatic video tracking we showed that Nematostella exhibits rhythmic circadian locomotor activity, which is persistent in constant dark, shifted or disrupted by external dark/light cues and maintained the same rate at two different temperatures. This activity was inhibited by a casein kinase 1δ/ε inhibitor, suggesting a role for CK1 homologue(s) in Nematostella clock. Using high-throughput sequencing we profiled Nematostella transcriptomes over 48 hours under a light-dark cycle. We identified 180 Nematostella diurnally-oscillated transcripts and compared them with previously established databases of adult and larvae of the symbiotic coral Acropora millepora, revealing both shared homologues and unique rhythmic genes. Taken together, this study further establishes Nematostella as a non-symbiotic model organism to study circadian rhythms and increases our understanding about the fundamental elements of circadian regulation and their evolution within the Metazoa.This work was supported by the Israel-US Binational Science Foundation to OL and AMT (Award 2011187). Additional support was provided by the WHOI Early Career Scientist Award to AMT