Salivary diagnostics is a rapidly advancing field that offers clinicians and patients the potential of rapid, noninvasive diagnostics with excellent accuracy. In order for the complete realization of the potential of saliva, however, extensive profiling of constituents must be conducted and diagnostic biomarkers must be thoroughly validated. This article briefly overviews the process of conducting a study of salivary biomarkers in a patient cohort and highlights the studies that have been conducted on different classes of molecules in the saliva. Emerging frontiers in salivary diagnostics research that may significantly advance the field will also be highlighted.

The Reelin-signaling pathway is essential for correct neuronal positioning within the central nervous system. Mutant mice with a deletion of Reelin, its lipoprotein receptors, or its intracellular adaptor protein Disabled-1 (Dab1), exhibit nociceptive abnormalities: thermal (heat) hyperalgesia and reduced mechanical sensitivity. To determine dorsal horn alterations associated with these nociceptive abnormalities, we first characterized the correctly positioned Dab1 neurons in wild-type and mispositioned neurons in Reelin-signaling pathway mutant lumbar spinal cord. Using immunofluorescence, we found that 70% of the numerous Dab1 neurons in Reln+/+ laminae I–II and 67% of those in the lateral reticulated area and lateral spinal nucleus co-express the LIM-homeobox transcription factor 1 beta (Lmx1b), an excitatory glutamatergic neuron marker. Evidence of Dab1- and Dab1-Lmx1b neuronal positioning errors was found within the isolectin B4 terminal region of Reln−/− lamina IIinner and in the lateral reticulated area and lateral spinal nucleus, where about 50% of the Dab1-Lmx1b neurons are missing. Importantly, Dab1-Lmx1b neurons in laminae I–II and the lateral reticulated area express Fos after noxious thermal or mechanical stimulation and thus participate in these circuits. In another pain relevant locus – the lateral cervical nucleus, we also found about a 50% loss of Dab1-Lmx1b neurons in Reln−/− mice. We suggest that extensively mispositioned Dab1 projection neurons in the lateral reticulated area, lateral spinal nucleus, and lateral cervical nucleus and the more subtle positioning errors of Dab1 interneurons in laminae I–II contribute to the abnormalities in pain responses found in Reelin-signaling pathway mutants.

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We present a Pedestrian Dominance Model (PDM) to identify the dominance characteristics of pedestrians for robot navigation. Through a perception study on a simulated dataset of pedestrians, PDM models the perceived dominance levels of pedestrians with varying motion behaviors corresponding to trajectory, speed, and personal space. At runtime, we use PDM to identify the dominance levels of pedestrians to facilitate socially-aware navigation for the robots. PDM can predict dominance levels from trajectories with~85% accuracy. Prior studies in psychology literature indicate that when interacting with humans, people are more comfortable around people that exhibit complementary movement behaviors. Our algorithm leverages this by enabling the robots to exhibit complementing responses to pedestrian dominance. We also present an application of PDM for generating dominance-based collision-avoidance behaviors in the navigation of autonomous vehicles among pedestrians. We demonstrate the benefits of our algorithm for robots navigating among tens of pedestrians in simulated environments.

Background: Molecular tweezers (MTs) are broad-spectrum inhibitors of abnormal protein aggregation. A lead MT, called CLR01, has been demonstrated to inhibit the aggregation and toxicity of multiple amyloidogenic proteins in vitro and in vivo. Previously, we evaluated the effect of CLR01 in the 3×Tg mouse model of Alzheimer’s disease, which overexpresses mutant human presenilin 1, amyloid β-protein precursor, and tau and found that subcutaneous administration of the compound for one month led to a robust reduction of amyloid plaques, neurofibrillary tangles, and microgliosis. CLR01 also has been demonstrated to inhibit tau aggregation in vitro and tau seeding in cell culture, yet because in Alzheimer’s disease (AD) and in the 3×Tg model, tau hyperphosphorylation and aggregation are thought to be downstream of Aβ insults, the study in this model left the question whether CLR01 affected tau in vivo directly or indirectly open.Methods: To determine if CLR01 could ameliorate tau pathology directly in vivo, we tested the compound similarly using the P301S-tau (line PS19) mouse model. Mice were administered 0.3- or 1.0-mg/Kg per day CLR01 and tested for muscle strength and behavioral deficits, including anxiety- and disinhibition-like behavior. Their brains then were analyzed by immunohistochemical and biochemical assays for pathological forms of tau, neurodegeneration, and glial pathology.Results: CLR01 treatment ameliorated muscle-strength deterioration, anxiety-, and disinhibition-like behavior. Improved phenotype was associated with decreased levels of pathologic tau forms, suggesting that CLR01 exerts a direct effect on tau in vivo. Limitations of the study included a relatively short treatment period of the mice at an age in which full pathology is not yet developed. In addition, high variability in this model lowered the statistical significance of the findings of some outcome measures.Conclusions: The findings suggest that CLR01 is a particularly attractive candidate for the treatment of AD because it targets simultaneously the two major pathogenic proteins instigating and propagating the disease, amyloid β-protein (Aβ) and tau, respectively. In addition, our study suggests that CLR01 can be used for the treatment of other tauopathies in the absence of amyloid pathology.