Odors modulate color appearance.

Our brain constantly combines multisensory information from our surrounding environment. Odors for instance are often perceived with visual cues; these sensations interact to form our own subjective experience. This integration process can have a profound impact on the resulting experience and can alter our subjective reality. Crossmodal correspondences are the consistent associations between stimulus features in different sensory modalities. These correspondences are presumed to be bidirectional in nature and have been shown to influence our perception in a variety of different sensory modalities. Vision is dominant in our multisensory perception and can influence how we perceive information in our other senses, including olfaction. We explored the effect that different odors have on human color perception by presenting olfactory stimuli while asking observers to adjust a color patch to be devoid of hue (neutral gray task). We found a shift in the perceived neutral gray point to be biased toward warmer colors. Four out of five of our odors also trend toward their expected crossmodal correspondences. For instance, when asking observers to perform the neutral gray task while presenting the smell of cherry, the perceptually achromatic stimulus was biased toward a red-brown. Using an achromatic adjustment task, we were able to demonstrate a small but systematic effect of the presence of odors on human color perception.

Physicochemical features partially explain olfactory crossmodal correspondences.

During the olfactory perception process, our olfactory receptors are thought to recognize specific chemical features. These features may contribute towards explaining our crossmodal perception. The physicochemical features of odors can be extracted using an array of gas sensors, also known as an electronic nose. The present study investigates the role that the physicochemical features of olfactory stimuli play in explaining the nature and origin of olfactory crossmodal correspondences, which is a consistently overlooked aspect of prior work. Here, we answer the question of whether the physicochemical features of odors contribute towards explaining olfactory crossmodal correspondences and by how much. We found a similarity of 49% between the perceptual and the physicochemical spaces of our odors. All of our explored crossmodal correspondences namely, the angularity of shapes, smoothness of textures, perceived pleasantness, pitch, and colors have significant predictors for various physicochemical features, including aspects of intensity and odor quality. While it is generally recognized that olfactory perception is strongly shaped by context, experience, and learning, our findings show that a link, albeit small (6-23%), exists between olfactory crossmodal correspondences and their underlying physicochemical features.

Predicting the crossmodal correspondences of odors using an electronic nose.

When designing multisensorial experiences, robustly predicting the crossmodal perception of olfactory stimuli is a critical factor. We investigate the possibility of predicting olfactory crossmodal correspondences using the underlying physicochemical features. An electronic nose was tuned to the crossmodal perceptual axis of olfaction and was used to foretell people's crossmodal correspondences between odors and the angularity of shapes, smoothness of texture, perceived pleasantness, pitch, and colors. We found that the underlying physicochemical features of odors could be used to predict people's crossmodal correspondences. The human-machine perceptual dimensions that correlated well are the angularity of shapes (r = 0.71), the smoothness of texture (r = 0.82), pitch (r = 0.70), and the lightness of color (r = 0.59). The human-machine perceptual dimensions that did not correlate well (r < 0.50) are the perceived pleasantness (r = 0.20) and the hue of the color (r = 0.42 & 0.44). All perceptual dimensions except for the perceived pleasantness could be robustly predicted (p-values < 0.0001) including the hue of color. While it is recognized that olfactory perception is strongly shaped by learning and experience, our findings suggest that there is a systematic and predictable link between the physicochemical features of odorous stimuli and crossmodal correspondences. These findings may provide a crucial building block towards the digital transmission of smell and enhancing multisensorial experiences with better designs as well as more engaging, and enriched experiences.

FluNet: An AI-Enabled Influenza-Like Warning System.

Influenza is an acute viral respiratory disease that is currently causing severe financial and resource strains worldwide. With the COVID-19 pandemic exceeding 153 million cases worldwide, there is a need for a low-cost and contactless surveillance system to detect symptomatic individuals. The objective of this study was to develop FluNet, a novel, proof-of-concept, low-cost and contactless device for the detection of high-risk individuals. The system conducts face detection in the LWIR with a precision rating of 0.98, a recall of 0.91, an F-score of 0.96, and a mean intersection over union of 0.74 while sequentially taking the temperature trend of faces with a thermal accuracy of ± 1 K. In parallel, determining if someone is coughing by using a custom lightweight deep convolutional neural network with a precision rating of 0.95, a recall of 0.92, an F-score of 0.94 and an AUC of 0.98. We concluded this study by testing the accuracy of the direction of arrival estimation for the cough detection revealing an error of ± 4.78°. If a subject is symptomatic, a photo is taken with a specified region of interest using a visible light camera. Two datasets have been constructed, one for face detection in the LWIR consisting of 250 images of 20 participants' faces at various rotations and coverings, including face masks. The other for the real-time detection of coughs comprised of 40,482 cough / not cough sounds. These findings could be helpful for future low-cost edge computing applications for influenza-like monitoring.

Analysis of non-conjugated steroids in water using paper spray mass spectrometry.

A novel strategy for the direct analysis of non-conjugated steroids in water using paper spray mass spectrometry (PS-MS) has been developed. PS-MS was used in the identification and quantification of non-conjugated (free) steroids in fish tank water samples. Data shown herein indicates that individual amounts of free steroids can be detected in aqua as low as; 0.17 ng/µL, 0.039 ng/µL, 0.43 ng/µL, 0.0076 ng/µL for aldosterone, corticosterone, cortisol, and ß-estrone, respectively, and with an average relative standard deviation of ca. < 10% in the positive ion mode using PS-MS/MS. Direct detection of free steroids in a raw water mixture, from aquaculture, without prior sample preparation is demonstrated. The presence of free steroids released in fish water samples was confirmed via tandem mass spectrometry using collision-induced dissociation. This approach shows promise for rapid and direct water quality monitoring to provide a holistic assessment of non-conjugated steroids in aqua.

Wnt and Notch signaling govern self-renewal and differentiation in a subset of human glioblastoma stem cells.

Developmental signal transduction pathways act diversely, with context-dependent roles across systems and disease types. Glioblastomas (GBMs), which are the poorest prognosis primary brain cancers, strongly resemble developmental systems, but these growth processes have not been exploited therapeutically, likely in part due to the extreme cellular and genetic heterogeneity observed in these tumors. The role of Wnt/ßcatenin signaling in GBM stem cell (GSC) renewal and fate decisions remains controversial. Here, we report context-specific actions of Wnt/ßcatenin signaling in directing cellular fate specification and renewal. A subset of primary GBM-derived stem cells requires Wnt proteins for self-renewal, and this subset specifically relies on Wnt/ßcatenin signaling for enhanced tumor burden in xenograft models. In an orthotopic Wnt reporter model, Wnthi GBM cells (which exhibit high levels of ßcatenin signaling) are a faster-cycling, highly self-renewing stem cell pool. In contrast, Wntlo cells (with low levels of signaling) are slower cycling and have decreased self-renewing potential. Dual inhibition of Wnt/ßcatenin and Notch signaling in GSCs that express high levels of the proneural transcription factor ASCL1 leads to robust neuronal differentiation and inhibits clonogenic potential. Our work identifies new contexts for Wnt modulation for targeting stem cell differentiation and self-renewal in GBM heterogeneity, which deserve further exploration therapeutically.

Multipotent CD15+ cancer stem cells in patched-1-deficient mouse medulloblastoma.

Subpopulations of tumorigenic cells have been identified in many human tumors, although these cells may not be very rare in some types of cancer. Here, we report that medulloblastomas arising from Patched-1-deficient mice contain a subpopulation of cells that show a neural precursor phenotype, clonogenic and multilineage differentiation capacity, activated Hedgehog signaling, wild-type Patched-1 expression, and the ability to initiate tumors following allogeneic orthotopic transplantation. The normal neural stem cell surface antigen CD15 enriches for the in vitro proliferative and in vivo tumorigenic potential from uncultured medulloblastomas, supporting the existence of a cancer stem cell hierarchy in this clinically relevant mouse model of cancer.

Cancer stem cells: at the headwaters of tumor development.

According to the cancer stem cell hypothesis, only a subpopulation of cells within a cancer has the capacity to sustain tumor growth. This subpopulation of cells is made up of cancer stem cells, which are defined simply as the population of cells within a tumor that can self-renew, differentiate, and regenerate a phenocopy of the cancer when injected in vivo. Cancer stem cells have now been prospectively isolated from human cancers of the blood, breast, and brain, and putative cancer stem cells have been identified from human skin, bone, and prostate tumors and from multiple established mammalian cancer cell lines. Furthermore, researchers are actively seeking cancer stem cells in every human cancer type. We present the current scientific evidence supporting the cancer stem cell hypothesis and discuss the experimental and therapeutic implications of the discovery of human cancer stem cells.

Chemical genetics reveals a complex functional ground state of neural stem cells.

The identification of self-renewing and multipotent neural stem cells (NSCs) in the mammalian brain holds promise for the treatment of neurological diseases and has yielded new insight into brain cancer. However, the complete repertoire of signaling pathways that governs the proliferation and self-renewal of NSCs, which we refer to as the 'ground state', remains largely uncharacterized. Although the candidate gene approach has uncovered vital pathways in NSC biology, so far only a few highly studied pathways have been investigated. Based on the intimate relationship between NSC self-renewal and neurosphere proliferation, we undertook a chemical genetic screen for inhibitors of neurosphere proliferation in order to probe the operational circuitry of the NSC. The screen recovered small molecules known to affect neurotransmission pathways previously thought to operate primarily in the mature central nervous system; these compounds also had potent inhibitory effects on cultures enriched for brain cancer stem cells. These results suggest that clinically approved neuromodulators may remodel the mature central nervous system and find application in the treatment of brain cancer.

Pharmacological telomerase inhibition can sensitize drug-resistant and drug-sensitive cells to chemotherapeutic treatment.

Effective strategies to reverse or prevent chemotherapeutic resistance are required before cancer therapies can be curative. Telomerase is the ribonucleoprotein responsible for de novo synthesis and maintenance of telomeres, and its activity is predominantly observed in cancer cells. The telomerase enzyme has been successfully inhibited or inactivated to sensitize cells to cellular stresses; however, no studies have determined yet the effect of combining a pharmacological inhibitor of telomerase catalysis and traditional chemotherapeutics for the treatment of drug-sensitive or drug-resistant cancers. Here, we describe the effect of 2-[(E)-3-naphtalen-2-yl-but-2-enoylamino]-benzoic acid (BIBR1532), a small-molecule inhibitor of telomerase catalytic activity, on drug-resistant leukemia and breast cancer cells and their parental counterparts when treated in combination with chemotherapeutics. We observed that BIBR1532-treated cells show progressive telomere shortening, decreased proliferative capacity, and sensitization to chemotherapeutic treatment. These effects are telomere length-dependent, because cells insensitive to BIBR1532 or cells released from telomerase inhibition did not demonstrate changes in growth ability or drug sensitivity. Our novel observations suggest that pharmacological telomerase inhibition in combination therapy may be a valid strategy for the treatment of both drug-sensitive and drug-resistant cancers.

An anchor site-type defect in human telomerase that disrupts telomere length maintenance and cellular immortalization.

Telomerase-mediated telomeric DNA synthesis is important for eukaryotic cell immortality. Telomerase adds tracts of short telomeric repeats to DNA substrates using a unique repeat addition form of processivity. It has been proposed that repeat addition processivity is partly regulated by a telomerase reverse transcriptase (TERT)-dependent anchor site; however, anchor site-mediating residues have not been identified in any TERT. We report the characterization of an N-terminal human TERT (hTERT) RNA interaction domain 1 (RID1) mutation that caused telomerase activity defects consistent with disruption of a template-proximal anchor site, including reduced processivity on short telomeric primers and reduced activity on substrates with nontelomeric 5' sequences, but not on primers with nontelomeric G-rich 5' sequences. This mutation was located within a subregion of RID1 previously implicated in biological telomerase functions unrelated to catalytic activity (N-DAT domain). Other N-DAT and C-terminal DAT (C-DAT) mutants and a C-terminally tagged hTERT-HA variant were defective in elongating short telomeric primers, and catalytic phenotypes of DAT variants were partially or completely rescued by increasing concentrations of DNA primers. These observations imply that RID1 and the hTERT C terminus contribute to telomerase's affinity for its substrate, and that RID1 may form part of the human telomerase anchor site.

Telomerase RNA mutated in autosomal dyskeratosis congenita reconstitutes a weakly active telomerase enzyme defective in telomere elongation.

Dyskeratosis congenita (DC) is a rare multi-system syndrome characterized by nail dystrophy, abnormal skin pigmentation and mucosal leukoplakia. The gene mutated in the X-linked form of human DC encodes for dyskerin, a nucleolar pseudourydilase that is involved in rRNA maturation. Dyskerin is also involved in telomerase function through its interaction with the telomerase RNA (hTR). Mutations in dyskerin result in low levels of hTR, decreased telomerase activity and telomere shortening. Autosomal dominant DC is characterized by mutations in hTR, supporting the hypothesis that the DC phenotype may be caused by impaired telomere maintenance. Several mutations have been identified in different regions of hTR in patients affected by autosomal dominant DC. Recent reports have shown that coexpression of wild-type hTR with hTR harboring mutations found in the pseudoknot domain does not affect telomerase activity in vitro. However, these studies did not assess the consequences of mutant hTR expression at the telomeres. Here we provide the first direct in vivo evidence that a mutant hTR carrying the GC to AG double substitution in the pseudoknot at nucleotides 107-108 found in patients affected by autosomal dominant DC does not behave as a dominant-negative for telomere maintenance. Rather it reconstitutes a weakly active telomerase enzyme, which is defective in telomere elongation.