Physically salient objects are thought to attract attention in natural scenes. However, research has shown that meaning maps, which capture the spatial distribution of semantically informative scene ...features, trump physical saliency in predicting the pattern of eye moments in natural scene viewing. Meaning maps even predict the fastest eye movements, suggesting that the brain extracts the spatial distribution of potentially meaningful scene regions very rapidly. To test this hypothesis, we applied representational similarity analysis to ERP data. The ERPs were obtained from human participants (
= 32, male and female) who viewed a series of 50 different natural scenes while performing a modified 1-back task. For each scene, we obtained a physical saliency map from a computational model and a meaning map from crowd-sourced ratings. We then used representational similarity analysis to assess the extent to which the representational geometry of physical saliency maps and meaning maps can predict the representational geometry of the neural response (the ERP scalp distribution) at each moment in time following scene onset. We found that a link between physical saliency and the ERPs emerged first (∼78 ms after stimulus onset), with a link to semantic informativeness emerging soon afterward (∼87 ms after stimulus onset). These findings are in line with previous evidence indicating that saliency is computed rapidly, while also indicating that information related to the spatial distribution of semantically informative scene elements is computed shortly thereafter, early enough to potentially exert an influence on eye movements.
Attention may be attracted by physically salient objects, such as flashing lights, but humans must also be able to direct their attention to meaningful parts of scenes. Understanding how we direct attention to meaningful scene regions will be important for developing treatments for disorders of attention and for designing roadways, cockpits, and computer user interfaces. Information about saliency appears to be extracted rapidly by the brain, but little is known about the mechanisms that determine the locations of meaningful information. To address this gap, we showed people photographs of real-world scenes and measured brain activity. We found that information related to the locations of meaningful scene elements was extracted rapidly, shortly after the emergence of saliency-related information.
Smoking of food is one of the oldest methods of food preservation and still is used widely to help preserve foods such as ham, bacon, sausage, fish, and cheeses. Apart from its conservation function, ...the smoking process also has a considerable influence on the sensory characteristics of the products. A highly trained, skilled descriptive sensory panel identified, defined, and referenced 14 attributes related to the flavor of food products labeled as smoked or smoky. The panel evaluated sauces, meats, fish, cheeses, vegetables, and flavorings that are on the market in addition to samples that were smoked in‐house. Attributes attributed to the smoke flavor in each sample were written down and discussed. The list was narrowed to include only those attributes that were thought to be specifically related to the smoke flavor and not to the base notes of the product or other cooked/processed notes. The lexicon includes: Smoky (Overall), Ashy, Woody, Musty/Dusty, Musty/Earthy, Burnt, Acrid, Pungent, Petroleum‐Like, Creosote/Tar, Cedar, Bitter, Metallic, and Sour. Definitions of these attributes were written and references were found that anchor a 0–15 point scale. The references include market products, chemical solutions and commonly found non‐food products. This lexicon can be used to evaluate the smoke flavor on all types of food products.
Practical applications
This research provides a list of sensory terms that can be used to describe the smoky flavor of products. The lexicon will help sensory analysts, product developers, researchers, and technologists better understand the flavor of products that have been naturally or artificially smoked to modify or improve the products.
Ozanimod (RPC1063) is a specific and potent small molecule modulator of the sphingosine 1-phosphate receptor 1 (S1PR1) and receptor 5 (S1PR5), which has shown therapeutic benefit in clinical trials ...of relapsing multiple sclerosis and ulcerative colitis. Ozanimod and its active metabolite, RP-101075, exhibit a similar specificity profile at the S1P receptor family in vitro and pharmacodynamic profile in vivo. The NZBWF1 mouse model was used in therapeutic dosing mode to assess the potential benefit of ozanimod and RP-101075 in an established animal model of systemic lupus erythematosus. Compared with vehicle-treated animals, ozanimod and RP-101075 reduced proteinuria over the duration of the study and serum blood urea nitrogen at termination. Additionally, ozanimod and RP-101075 reduced kidney disease in a dose-dependent manner, as measured by histological assessment of mesangial expansion, endo- and exo-capillary proliferation, interstitial infiltrates and fibrosis, glomerular deposits, and tubular atrophy. Further exploration into gene expression changes in the kidney demonstrate that RP-101075 also significantly reduced expression of fibrotic and immune-related genes in the kidneys. Of note, RP-101075 lowered the number of plasmacytoid dendritic cells, a major source of interferon alpha in lupus patients, and reduced all B and T cell subsets in the spleen. Given the efficacy demonstrated by ozanimod and its metabolite RP-101075 in the NZBWF1 preclinical animal model, ozanimod may warrant clinical evaluation as a potential treatment for systemic lupus erythematosus.
The capability of measuring the complex permittivity of tissues has the potential to provide valuable new insights to inform medical assessment and diagnosis. However, existing electrical impedance ...approaches have practical limitations when aiming to measure tissues' anisotropy with accuracy. Here we present new methods that overcome the limitations of previous approaches by modeling the anisotropy in both the resistivity and reactivity of tissues measured in three or more different directions. These new methods are validated with numerical simulations and in situ experiments on healthy ovine skeletal muscle. The obtained data between 3 kHz and 1 MHz are also made publicly available in the supplementary information.
The prospect of replacing damaged body parts with artificial implants is being transformed from science fiction to science fact through the increasing application of electronics to interface with ...human neurons in the limbs, the brain, and the retina. We propose bio-inspired electronics which adopt the fractal geometry of the neurons they interface with. Our focus is on retinal implants, although performance improvements will be generic to many neuronal types. The key component is a multifunctional electrode; light passes through this electrode into a photodiode which charges the electrode. Its electric field then stimulates the neurons. A fractal electrode might increase both light transmission and neuron proximity compared to conventional Euclidean electrodes. These advantages are negated if the fractal's field is less effective at stimulating neurons. We present simulations demonstrating how an interplay of fractal properties generates enhanced stimulation; the electrode voltage necessary to stimulate all neighboring neurons is over 50% less for fractal than Euclidean electrodes. This smaller voltage can be achieved by a single diode compared to three diodes required for the Euclidean electrode's higher voltage. This will allow patients, for the first time, to see with the visual acuity necessary for navigating rooms and streets.
How regular physical activity is able to improve health remains poorly understood. The release of factors from skeletal muscle following exercise has been proposed as a possible mechanism mediating ...such systemic benefits. We describe a mechanism wherein skeletal muscle, in response to a hypertrophic stimulus induced by mechanical overload (MOV), released extracellular vesicles (EVs) containing muscle‐specific miR‐1 that were preferentially taken up by epidydimal white adipose tissue (eWAT). In eWAT, miR‐1 promoted adrenergic signaling and lipolysis by targeting Tfap2α, a known repressor of Adrβ3 expression. Inhibiting EV release prevented the MOV‐induced increase in eWAT miR‐1 abundance and expression of lipolytic genes. Resistance exercise decreased skeletal muscle miR‐1 expression with a concomitant increase in plasma EV miR‐1 abundance, suggesting a similar mechanism may be operative in humans. Altogether, these findings demonstrate that skeletal muscle promotes metabolic adaptations in adipose tissue in response to MOV via EV‐mediated delivery of miR‐1.
Development of reliable, easy-to-use, rapid diagnostic tests (RDTs) to detect glucose-6-phosphate dehydrogenase (G6PD) deficiency at point of care is essential to deploying primaquine therapies as ...part of malaria elimination strategies. We assessed a kit under research and development called CareStart™ G6PD deficiency screening test (Access Bio, New Jersey, USA) by comparing its performance to quantitative G6PD enzyme activity using a standardized spectrophotometric method ('gold standard'). Blood samples (n = 903) were collected from Cambodian adults living in Pailin province, western Cambodia. G6PD enzyme activities ranged from 0 to 20.5 U/g Hb (median 12.0 U/g Hg). Based on a normal haemoglobin concentration and wild-type G6PD gene, the normal values of G6PD enzymatic activity for this population was 3.6 to 20.5 U/g Hg (95(th) percentiles from 5.5 to 17.2 U/g Hg). Ninety-seven subjects (10.7%) had <3.6 U/g Hg and were classified as G6PD deficient. Prevalence of deficiency was 15.0% (64/425) among men and 6.9% (33/478) among women. Genotype was analyzed in 66 G6PD-deficient subjects and 63 of these exhibited findings consistent with Viangchang genotype. The sensitivity and specificity of the CareStart™ G6PD deficiency screening test was 0.68 and 1.0, respectively. Its detection threshold was <2.7 U/g Hg, well within the range of moderate and severe enzyme deficiencies. Thirteen subjects (1.4%, 12 males and 1 female) with G6PD enzyme activities <2 U/g Hg were falsely classified as "normal" by RDT. This experimental RDT test here evaluated outside of the laboratory for the first time shows real promise, but safe application of it will require lower rates of falsely "normal" results.
BackgroundDespite some successes with checkpoint inhibitors for treating cancer, most patients remain refractory to treatment, possibly due to the inhibitory nature of the tumor stroma that impedes ...the function and entry of effector cells. We devised a new technique of combining immunotherapy with radiotherapy (XRT), more specifically low-dose XRT, to overcome the stroma and maximize systemic outcomes.MethodsWe bilaterally established 344SQ lung adenocarcinoma tumors in 129Sv/Ev mice. Primary and secondary tumors were irradiated with either high-dose or low-dose of XRT with systemic anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte associated protein 4 administration. Survival and tumor growth were monitored for the various groups, and secondary tumors were phenotyped by flow cytometry for immune populations. Tumor growth factor-beta (TGF-β) cytokine levels were assessed locally after low-dose XRT, and specific immune-cell depletion experiments were conducted to identify the major contributors to the observed systemic antitumor effect.ResultsThrough our preclinical and clinical studies, we observed that when tumor burden was high, there was a necessity of combining high-dose XRT to ‘prime’ T cells at the primary tumor site, with low-dose XRT directed to secondary (metastatic) tumors to ‘modulate the stroma’. Low-dose XRT improved the antitumor outcomes of checkpoint inhibitors by favoring M1 macrophage polarization, enhancing natural killer (NK) cell infiltration, and reducing TGF-β levels. Depletion of CD4+ T cells and NK cells abrogated the observed antitumor effect.ConclusionOur data extend the benefits of low-dose XRT to reprogram the tumor environment and improve the infiltration and function of effector immune cells into secondary tumors.
Sex is an important factor in mental health, and a non-binary view of how variation in sex and gender influence mental health represents a new research frontier that may yield new insights. The ...recent acceleration of research into sexual orientation, gender identity, and mental health has generally been conducted without sufficient understanding of the opinions of sexual and gender minorities (SGM) toward this research. We surveyed 768 individuals, with an enrichment of LGBTQ+ stakeholders, for their opinions regarding genetic research of SGM and mental health. We found that the key predictors of attitudes toward genetic research specifically on SGM are 1) general attitudes toward genetic and mental health research 2) tolerance of SGM and associated behaviors and 3) age of the participant. Non-heterosexual stakeholder status was significantly associated with increased willingness to participate in genetic research if a biological basis for gender identity were discovered. We also found that heterosexual, cisgender participants with a low tolerance for SGM indicated their SGM views would be positively updated if science showed a biological basis for their behaviors and identities. These findings represent an important first step in understanding and engaging the LGBTQ+ stakeholder community in the context of genetic research.
Leaves and floral organs are polarized along their adaxial-abaxial (dorsal-ventral) axis. In Arabidopsis, this difference is particularly obvious in the first two rosette leaves, which possess ...trichomes (leaf hairs) on their adaxial surface but not their abaxial surface. Mutant alleles of KANADI (KAN) were identified in a screen for mutants that produce abaxial trichomes on these first two leaves. kan mutations were originally identified as enhancers of the mutant floral phenotype of crabs claw (crc), a gene that specifies abaxial identity in carpels. Here we show that KAN is required for abaxial identity in both leaves and carpels, and encodes a nuclear-localized protein in the GARP family of putative transcription factors. The expression pattern of KAN messenger RNA and the effect of ectopically expressing KAN under the regulation of the cauliflower mosaic virus (CAMV) 35S promoter indicate that KAN may also specify peripheral identity in the developing embryo.
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