Sagit Shushan

Human Tears Contain a Chemosignal

Merely sniffing womens negative emotional tears reduces sexual arousal in men. Emotional tearing is a poorly understood behavior that is considered uniquely human. In mice, tears serve as a chemosignal. We therefore hypothesized that human tears may similarly serve a chemosignaling function. We found that merely sniffing negative-emotion–related odorless tears obtained from women donors induced reductions in sexual appeal attributed by men to pictures of women’s faces. Moreover, after sniffing such tears, men experienced reduced self-rated sexual arousal, reduced physiological measures of arousal, and reduced levels of testosterone. Finally, functional magnetic resonance imaging revealed that sniffing women’s tears selectively reduced activity in brain substrates of sexual arousal in men.

Neural activity at the human olfactory epithelium reflects olfactory perception

Organization of receptive surfaces reflects primary axes of perception. In vision, retinal coordinates reflect spatial coordinates. In audition, cochlear coordinates reflect tonal coordinates. However, the rules underlying the organization of the olfactory receptive surface are unknown. To test the hypothesis that organization of the olfactory epithelium reflects olfactory perception, we inserted an electrode into the human olfactory epithelium to directly measure odorant-induced evoked responses. We found that pairwise differences in odorant pleasantness predicted pairwise differences in response magnitude; that is, a location that responded maximally to a pleasant odorant was likely to respond strongly to other pleasant odorants, and a location that responded maximally to an unpleasant odorant was likely to respond strongly to other unpleasant odorants. Moreover, the extent of an individuals perceptual span predicted their span in evoked response. This suggests that, similarly to receptor surfaces for vision and audition, organization of the olfactory receptor surface reflects key axes of perception.

A role for TENM1 mutations in congenital general anosmia

Congenital general anosmia (CGA) is a neurological disorder entailing a complete innate inability to sense odors. While the mechanisms underlying vertebrate olfaction have been studied in detail, there are still gaps in our understanding of the molecular genetic basis of innate olfactory disorders. Applying whole‐exome sequencing to a family multiply affected with CGA, we identified three members with a rare X‐linked missense mutation in the TENM1 (teneurin 1) gene (ENST00000422452:c.C4829T). In Drosophila melanogaster, TENM1 functions in synaptic‐partner‐matching between axons of olfactory sensory neurons and target projection neurons and is involved in synapse organization in the olfactory system. We used CRISPR‐Cas9 system to generate a Tenm1 disrupted mouse model. Tenm1−/− and point‐mutated Tenm1A/A adult mice were shown to have an altered ability to locate a buried food pellet. Tenm1A/A mice also displayed an altered ability to sense aversive odors. Results of our study, that describes a new Tenm1 mouse, agree with the hypothesis that TENM1 has a role in olfaction. However, additional studies should be done in larger CGA cohorts, to provide statistical evidence that loss‐of‐function mutations in TENM1 can solely cause the disease in our and other CGA cases.

Individual olfactory perception reveals meaningful nonolfactory genetic information

Significance Cyrano de Bergerac observed that “a large nose is the mark of a witty, courteous, affable, generous and liberal man.” Here we report that individual noses, not how they look but rather how they function, indeed say a lot about a person. Each person expresses a nearly unique set of different olfactory receptor genes, and therefore may have unique olfactory perception. We developed a highly sensitive perceptual test we call the “olfactory fingerprint” that captures this variability. Individual olfactory fingerprints are therefore mirrors of individual olfactory genomes. We demonstrate that such fingerprints predict genetic features linked to the olfactory system, such as aspects of immune regulation. Thus, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information. Each person expresses a potentially unique subset of ∼400 different olfactory receptor subtypes. Given that the receptors we express partially determine the odors we smell, it follows that each person may have a unique nose; to capture this, we devised a sensitive test of olfactory perception we termed the “olfactory fingerprint.” Olfactory fingerprints relied on matrices of perceived odorant similarity derived from descriptors applied to the odorants. We initially fingerprinted 89 individuals using 28 odors and 54 descriptors. We found that each person had a unique olfactory fingerprint (P < 10−10), which was odor specific but descriptor independent. We could identify individuals from this pool using randomly selected sets of 7 odors and 11 descriptors alone. Extrapolating from this data, we determined that using 34 odors and 35 descriptors we could individually identify each of the 7 billion people on earth. Olfactory perception, however, fluctuates over time, calling into question our proposed perceptual readout of presumably stable genetic makeup. To test whether fingerprints remain informative despite this temporal fluctuation, building on the linkage between olfactory receptors and HLA, we hypothesized that olfactory perception may relate to HLA. We obtained olfactory fingerprints and HLA typing for 130 individuals, and found that olfactory fingerprint matching using only four odorants was significantly related to HLA matching (P < 10−4), such that olfactory fingerprints can save 32% of HLA tests in a population screen (P < 10−6). In conclusion, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information.

From Nose to Brain: Un-Sensed Electrical Currents Applied in the Nose Alter Activity in Deep Brain Structures

Rules linking patterns of olfactory receptor neuron activation in the nose to activity patterns in the brain and ensuing odor perception remain poorly understood. Artificially stimulating olfactory neurons with electrical currents and measuring ensuing perception may uncover these rules. We therefore inserted an electrode into the nose of 50 human volunteers and applied various currents for about an hour in each case. This induced assorted non-olfactory sensations but never once the perception of odor. To validate contact with the olfactory path, we used functional magnetic resonance imaging to measure resting-state brain activity in 18 subjects before and after un-sensed stimulation. We observed stimulation-induced neural decorrelation specifically in primary olfactory cortex, implying contact with the olfactory path. These results suggest that indiscriminate olfactory activation does not equate with odor perception. Moreover, this effort serendipitously uncovered a novel path for minimally invasive brain stimulation through the nose.

Smelling Pseudomonas aeruginosa infections using a whole-cell biosensor – An alternative for the gold-standard culturing assay

Improved easy-to-use diagnostic tools for infections are in strong demand worldwide. Yet, despite dramatic advances in diagnostic technologies, the gold-standard remains culturing. Here we offer an alternative tool demonstrating that a bacterial biosensor can efficiently detect Pseudomonas aeruginosa infections in patients suffering from otitis externa. Detection was based on specific binding between the biosensor and 2-aminoacetophenone (2-AA), a volatile produced by P. aeruginosa in high amounts. We collected pus samples from ears of 26 subjects exhibiting symptoms of otitis externa. Detection of P. aeruginosa using the biosensor was compared to detection using gold-standard culturing assay and to gas-chromatograph-mass-spectrometry (GC-MS) analyses of 2-AA. The biosensor strain test matched the culture assay in 24 samples (92%) and the GC-MS analyses in 25 samples (96%). With this result in hand, we designed a device containing a whole-cell luminescent biosensor combined with a photo-multiplier tube. This device allowed detection of 2-AA at levels as low as 2 nmol, on par with detection level of GC-MS. The results of the described study demonstrate that the volatile 2-AA serves as an effective biomarker for P. aeruginosa in ear infections, and that activation of the biosensor strain by 2-AA provides a unique opportunity to design an easy-to-use device that can specifically detect P. aeruginosa infections.

Using a Sniff Controller to Self-Trigger Abdominal Functional Electrical Stimulation for Assisted Coughing Following Cervical Spinal Cord Lesions

Individuals with cervical spinal cord lesions (SCLs) typically depend on caregivers to manually assist in coughing by pressing against their abdominal wall. Coughing can also be assisted by functional electric stimulation (FES) applied to abdominal muscles via surface electrodes. Efficacy of FES, however, depends on precise temporal synchronization. The sniff controller is a trigger that enables paralyzed individuals to precisely control external devices through alterations in nasal airflow. We hypothesized that FES self-triggering by sniff controller may allow for effective cough timing. After optimizing parameters in 16 able-bodied subjects, we measured peak expiratory flow (PEF) in 14 subjects with SCL who coughed with or without assistance. Assistance was either manual assistance of a caregiver, caregiver activated FES, button self-activated FES (for SCL participants who could press a button), or sniff-controlled self-activated FES. We found that all assisted methods provided equally effective improvements, increasing PEF on average by 25 ± 27%

Next-generation sequencing of patients with congenital anosmia

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Disinhibition of olfaction: Human olfactory performance improves following low levels of alcohol

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Functional Brain Imaging of Human Olfaction

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