Functions of human olfactory mucus and age-dependent changes.

Odorants are detected by olfactory sensory neurons, which are covered by olfactory mucus. Despite the existence of studies on olfactory mucus, its constituents, functions, and interindividual variability remain poorly understood. Here, we describe a human study that combined the collection of olfactory mucus and olfactory psychophysical tests. Our analyses revealed that olfactory mucus contains high concentrations of solutes, such as total proteins, inorganic elements, and molecules for xenobiotic metabolism. The high concentrations result in a capacity to capture or metabolize a specific repertoire of odorants. We provide evidence that odorant metabolism modifies our sense of smell. Finally, the amount of olfactory mucus decreases in an age-dependent manner. A follow-up experiment recapitulated the importance of the amount of mucus in the sensitive detection of odorants by their receptors. These findings provide a comprehensive picture of the molecular processes in olfactory mucus and propose a potential cause of olfactory decline.

Fast and reliable technique for spatial coherence measurement with a temporally modulated nonredundant slit array.

We propose a method of measuring the spatial coherence of light by means of a temporally modulated nonredundant slit array implemented on a digital micromirror device. We first formulate the theory of the spatial coherence measurement to incorporate a general case when the observation plane is not necessarily placed in the far field of the slit array. We then demonstrate experimentally that a single measurement determines the spatial coherence for 15 different slit separations accurately, even if background light is unavoidable, under the condition that a nonredundant array of six slits is illuminated evenly. These results clearly show that fast and highly reliable spatial coherence measurement is achievable with the proposed method without any difficulties.

100 years of Emil Wolf: introduction.

The groundbreaking research and ideas introduced by Emil Wolf continue to inspire researchers and motivate ongoing research in the wave properties of light. This special issue commemorates the legacy of Emil Wolf with research in physical optics, with specific focus on those areas where Wolf was active, such as optical coherence theory, inverse problems, singular optics, imaging, and polarization, and the intersection of these fields of study. Here we discuss the life of Emil Wolf and his influence on optical science and the optics community.

Effectiveness and Safety of Rehabilitation for Pediatric Patients with Nephrotic Syndrome in the Acute Phase: A Case Study.

Background: Exercise therapy for patients with pediatric nephrotic syndrome is necessary to improve physical function to maintain the patient's activities of daily life and school life while managing the risk of relapse; however, few studies have examined exercise therapy in the acute phase of the syndrome. This case study aimed to evaluate the efficacy and safety of exercise therapy in a patient with acute pediatric nephrotic syndrome being treated with steroids. Case: The patient was a 10-year-old boy diagnosed with primary nephrotic syndrome. Prednisolone (50 mg) was started on the 3rd day of hospitalization. Exercise therapy (moderate-intensity, 40 min, five times a week) was started on the 15th day. The urine protein/creatinine ratio from the 15th day (at the start of rehabilitation) to discharge decreased from 1.1  to 0.4, with no recurrence of nephrotic syndrome. At the initial, middle, and final evaluations, respectively, the grip strength was 10.1, 8.9, and 8.3 kg; the knee extension strength was 0.38, 0.46, and 0.45 kgf/kg; the sit-up test results were 18, 18, and 15 times; the side-step test results were 34, 36, and 31 times; the sit-and-reach test results were 22.9, 24.5, and 23.8 cm; and the 6-min walk test results were 420, 490, and 520 m. Leg muscle strength and exercise tolerance improved, but upper limb strength, trunk muscle strength, and agility decreased. Discussion: Moderate-intensity exercises may be effective and safe for pediatric patients with nephrotic syndrome in the acute phase. Exercise therapy may be beneficial to improve physical function and prevent decline during hospitalization in pediatric nephrotic syndrome patients.

Investigation of presenteeism, physical function, and exercise habits in workers with CKD: three case reports with literature review.

Management of presenteeism in the context of chronic kidney disease (CKD) is essential for disease management, ensuring the workforce's availability, and reducing health-related costs. The purpose of this case study was to investigate presenteeism, physical function, and exercise habits in three working patients with CKD and discuss their effects. Case 1 was a 71-year-old male security guard; Case 2 was a 72-year-old male agricultural worker; and Case 3 was an 83-year-old male civil engineering employee. Presenteeism was measured using the work functioning impairment scale (WFun), and physical function was measured using grip strength, skeletal muscle mass index, 10 m walk test, short physical performance battery, and exercise habits. The WFun assessment showed that only Case 3 had moderate presenteeism, and the barrier to employment was fatigue. Each value of physical function was higher than the reference value, but Case 3 had the lowest physical function values. All three patients had no exercise habits and were in the interest stage of behavior change. This case report indicates the existence of workers with CKD who need care for presenteeism, even if they have no problems with physical function or activities of daily living. To ensure work productivity in workers with CKD, clinicians may need to evaluate presenteeism, physical function, and exercise habits in addition to popular treatment and care.

Factors affecting health-related quality of life in older patients with chronic kidney disease: a single-center cross-sectional study.

BACKGROUND: Health-related quality of life (HRQoL) assessment is important for patients with chronic kidney disease (CKD). However, few studies have examined factors related to HRQoL, such as physical function, in older patients with predialysis CKD. This study evaluated the relationship between physical function, renal function, and nutritional status on the HRQoL in this patient group. METHODS: This cross-sectional study included 61 patients aged ≥ 65 years with stages 3-5 predialysis CKD who were admitted for CKD education purposes. Using the EuroQoL 5-dimension 5-level (EQ-5D-5L) health status measure, the percentages of each EQ-5D-5L item were investigated. Physical function was measured using the short physical performance battery (SPPB) and grip strength, and characteristics, such as age, sex, diabetes mellitus, estimated glomerular filtration rate, and Geriatric Nutrition Risk Index, were investigated. Factors associated with EQ-5D-5L were identified using multiple regression analysis. RESULTS: More than half of respondents (34/61, 55.7%) selected the second or higher level "have a problem" for the pain/discomfort section. The EQ-5D-5L score was significantly correlated with grip strength (r = 0.34, p = 0.01) and SPPB (r = 0.59, p = 0.00) in a single correlation analysis. Only SPPB (ß = 0.67, p = 0.00) remained a significant factor after adjustment for grip strength, SPPB, age, sex, diabetes mellitus, and estimated glomerular filtration rate. CONCLUSION: Physical function may be an important factor influencing HRQoL in older patients with predialysis CKD.

Spatial coherence measurement via a digital micromirror device based spatiotemporal light modulation.

We propose a method for measuring the spatial coherence of light by means of temporal modulation of a double slit displayed on a digital micromirror device. It is demonstrated theoretically and experimentally that the technique is generally insensitive to background light, and thus its suppression or subtraction is not necessary. Moreover, the visibility of the interference fringe pattern can be enhanced by modulating only either one of the two slits. These favorable features enable one to measure the spatial coherence of even faint light more conveniently and accurately.

Immunosuppressive effect of a non-proteinogenic amino acid from Streptomyces through inhibiting allogeneic T cell proliferation.

The immunosuppressive activity of myriocin (ISP-1), a lead compound of fingolimod (FTY720), is derived from its 2-amino-1,3-propandiol structure. A non-proteinogenic amino acid, (2S,6R)-diamino-(5R,7)-dihydroxy-heptanoic acid (DADH), that contains this structure, was recently identified as a biosynthetic intermediate of a dipeptide secondary metabolite, vazabitide A, in Streptmyces sp. SANK 60404; however its effect on adaptive immunity has not yet been examined. In this study, we examined whether DADH suppresses mixed lymphocyte reaction using mouse bone marrow-derived dendritic cells (BMDCs) and allogeneic splenic T cells. Although T cell proliferation induced by cross-linking CD3 and CD28 were not suppressed by DADH unlike ISP-1, the pre-incubation of BMDCs with DADH but not ISP-1 significantly decreased allogeneic CD8+ T cell expansion. Based on these results, we concluded that DADH suppresses DC-mediated T cell activation by targeting DCs.

(ADP-ribosyl)hydrolases: Structural Basis for Differential Substrate Recognition and Inhibition.

Protein ADP-ribosylation is a highly dynamic post-translational modification. The rapid turnover is achieved, among others, by ADP-(ribosyl)hydrolases (ARHs), an ancient family of enzymes that reverses this modification. Recently ARHs came into focus due to their role as regulators of cellular stresses and tumor suppressors. Here we present a comprehensive structural analysis of the enzymatically active family members ARH1 and ARH3. These two enzymes have very distinct substrate requirements. Our data show that binding of the adenosine ribose moiety is highly diverged between the two enzymes, whereas the active sites harboring the distal ribose closely resemble each other. Despite this apparent similarity, we elucidate the structural basis for the selective inhibition of ARH3 by the ADP-ribose analogues ADP-HPD and arginine-ADP-ribose. Together, our biochemical and structural work provides important insights into the mode of enzyme-ligand interaction, helps to understand differences in their catalytic behavior, and provides useful tools for targeted drug design.

Monitoring Poly(ADP-ribosyl)glycohydrolase Activity with a Continuous Fluorescent Substrate.

The post-translational modification (PTM) and signaling molecule poly(ADP-ribose) (PAR) has an impact on diverse biological processes. This PTM is regulated by a series of ADP-ribosyl glycohydrolases (PARG enzymes) that cleave polymers and/or liberate monomers from their protein targets. Existing methods for monitoring these hydrolases rely on detection of the natural substrate, PAR, commonly achieved via radioisotopic labeling. Here we disclose a general substrate for monitoring PARG activity, TFMU-ADPr, which directly reports on total PAR hydrolase activity via release of a fluorophore; this substrate has excellent reactivity, generality (processed by the major PARG enzymes), stability, and usability. A second substrate, TFMU-IDPr, selectively reports on PARG activity only from the enzyme ARH3. Use of these probes in whole-cell lysate experiments has revealed a mechanism by which ARH3 is inhibited by cholera toxin. TFMU-ADPr and TFMU-IDPr are versatile tools for assessing small-molecule inhibitors in vitro and probing the regulation of ADP-ribosyl catabolic enzymes.

Identification of a Novel TRPM8 Agonist from Nutmeg: A Promising Cooling Compound.

The transient receptor potential melastatin 8 (TRPM8) ion channel is the primary receptor for innocuous cold stimuli (<28 °C) in humans. TRPM8 agonists such as l-(-)-menthol are widely used as flavors and additives to impart briskness, in addition to medicinal uses for inflammation and pain. Though various natural and synthetic agonists have been explored, only few natural compounds are known. We report herein the identification and characterization of the novel neolignan agonist erythro- and threo-Δ8'-7-ethoxy-4-hydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan (1) with an EC50 of 0.332 µM, which was isolated from a well-known spice, nutmeg (Myristica fragrans Houtt.). Structure activity relationships are also disclosed, showing that the 7-d-menthoxy derivative is the most potent agonist (EC50 = 11 nM). The combination of 1 and l-(-)-menthol has an additive effect, suggesting that neolignan compounds interact with TRPM8 at different sites from those of l-(-)-menthol.

Predictive compound accumulation rules yield a broad-spectrum antibiotic.

Most small molecules are unable to rapidly traverse the outer membrane of Gram-negative bacteria and accumulate inside these cells, making the discovery of much-needed drugs against these pathogens challenging. Current understanding of the physicochemical properties that dictate small-molecule accumulation in Gram-negative bacteria is largely based on retrospective analyses of antibacterial agents, which suggest that polarity and molecular weight are key factors. Here we assess the ability of over 180 diverse compounds to accumulate in Escherichia coli. Computational analysis of the results reveals major differences from the retrospective studies, namely that the small molecules that are most likely to accumulate contain an amine, are amphiphilic and rigid, and have low globularity. These guidelines were then applied to convert deoxynybomycin, a natural product that is active only against Gram-positive organisms, into an antibiotic with activity against a diverse panel of multi-drug-resistant Gram-negative pathogens. We anticipate that these findings will aid in the discovery and development of antibiotics against Gram-negative bacteria.

Intensity-interferometric spectral-domain optical coherence tomography with dispersion cancellation.

We describe a technique for cancelling group-velocity dispersion in spectral-domain (SD) optical coherence tomography (OCT) based on classical intensity correlations. As a classical analogue of quantum OCT, a Hong-Ou-Mandel interferometer is combined with a conventional SD-OCT setup, and correlations between different spectral intensities are calculated. It is shown theoretically that a simple computational procedure used in SD-OCT enables scanless cross-sectional imaging with both dispersion cancellation and a factor-of-√2 resolution enhancement. The method involves no ultrafast detectors and works with common light sources.

Chiroptical control in helical receptor-anion complexes.

Dimers of appropriately arranged anion-responsive π-conjugated moieties form helical structures by interaction with chiral anions. Terphenyl-bridged dimers of dipyrrolyldiketone boron complexes show chirality induced by binding l-amino acid anions, as observed by circular dichroism (CD) and circularly polarized luminescence (CPL). The preferred configurations of helical structures depend on the geometries of the terphenyl spacer moieties.

Anion-driven structures of radially arranged anion receptor oligomers.

Radially arranged oligomers of π-conjugated acyclic anion receptors showed various anion-driven structures depending on the positions and numbers of the receptor units.

Resolution improvement in spectral-domain optical coherence tomography based on classical intensity correlations.

We describe a resolution-improved spectral-domain (SD) optical coherence tomography (OCT) based on classical intensity correlations as a counterpart of the recently proposed intensity-based time-domain OCT. Similarly to quantum OCT, the setup employs the Hong-Ou-Mandel interferometer at the output of the conventional SD-OCT. It is shown theoretically that a factor-of-√2 improvement in axial resolution is obtained with this arrangement. Some unique and useful features of our proposed system are addressed.

Image quality in double- and triple-intensity ghost imaging with classical partially polarized light.

Classical ghost imaging is a correlation-imaging technique in which the image of the object is found through intensity correlations of light. We analyze three different quality parameters, namely the visibility, the signal-to-noise ratio (SNR), and the contrast-to-noise ratio (CNR), to assess the performance of double- and triple-intensity correlation-imaging setups. The source is a random partially polarized beam of light obeying Gaussian statistics, and the image quality is evaluated as a function of the degree of polarization (DoP). We show that the visibility improves when the DoP and the order of imaging increase, while the SNR behaves oppositely. The CNR is for the most part independent of DoP and the imaging order. The results are important for the development of new imaging devices using partially polarized light.

Oximetry of retinal capillaries by multicomponent analysis.

Retinal oximetry of capillaries was performed for early detection of retinal vascular abnormalities, which are caused predominantly by complications of systemic circulatory diseases. As the conventional method for determining absorbance is not applicable to capillaries, multicomponent analysis was used to estimate the absorbance spectra of the retinal blood vessels. In this analysis, the capillary spectrum was classified as intermediate between those of the retinal arteries and veins, enabling relative estimation of oxygen saturation in the capillaries. This method could be useful for early recognition of disturbances in the peripheral circulation. Furthermore, a spectroscopic ophthalmoscope system based on the proposed method was developed to examine the human retina. A clinical trial of this system demonstrated that oximetry of the retinal capillaries may be an improvement over the present diagnosis for patients of malignant hypertension.

Imaging through an aberrating medium with classical ghost diffraction.

We describe a method for image transmission through an aberrating medium by means of a modified configuration for conventional ghost diffraction with classical incoherent beams. On the basis of optical coherence theory, we show that the effects of phase disturbances, be they deterministic or random, can be canceled out in our method and the squared modulus of the Fourier transform of the object is obtained in terms of intensity-correlation measurements. From the measurement data, the object can be reconstructed using standard phase retrieval algorithms.

Two new indole alkaloids, 2-(3,3-dimethylprop-1-ene)-costaclavine and 2-(3,3-dimethylprop-1-ene)-epicostaclavine, from the marine-derived fungus Aspergillus fumigatus.

Two new indole alkaloids, 2-(3,3-dimethylprop-1-ene)-costaclavine (1) and 2-(3,3-dimethylprop-1-ene)-epicostaclavine (2), together with the known compounds costaclavine (3), fumgaclavine A (4) and C (5), were isolated from the marine-derived fungus Aspergillus fumigatus. The planar structures of the two new compounds were elucidated on the basis of chemical and physicochemical evidence including MS, UV, IR and NMR spectra. Their stereochemistry was studied by NOESY, (1)H-(1)H coupling constant and CD spectra. The compounds 1, 2, 3 and 5 showed weak cytotoxicity against a mouse leukemia cell line (P388).