Molecular mechanism of anion permeation through aquaporin 6.

Aquaporins (AQPs) are recognized as transmembrane water channels that facilitate selective water permeation through their monomeric pores. Among the AQP family, AQP6 has an intriguing characteristic as an anion channel, which is allosterically controlled by pH conditions and is eliminated by a single amino acid mutation. However, the molecular mechanism of anion permeation through AQP6 remains unclear. Using molecular dynamics simulations in the presence of a transmembrane voltage utilizing an ion concentration gradient, we show that chloride ions permeate through the pore corresponding to the central axis of the AQP6 homotetramer. Under low pH conditions, a subtle opening of the hydrophobic selectivity filter (SF), located near the extracellular part of the central pore, becomes wetted and enables anion permeation. Our simulations also indicate that a single mutation (N63G) in human AQP6, located at the central pore, significantly reduces anion conduction, consistent with experimental data. Moreover, we demonstrate that the pH-sensing mechanism in which the protonation of H184 and H189 under low pH conditions allosterically triggers the gating of the SF region. These results suggest a unique pH-dependent allosteric anion permeation mechanism in AQP6 and could clarify the role of the central pore in some of the AQP tetramers.

Estimation of the relationship between the thermal environment of a house in winter and its occupants' health.

This study aims to quantify the relationship between the arbitrary thermal environment of houses in winter and their occupants' health through a comprehensive questionnaire survey, involving approximately 24,000 individuals who moved into insulated dwellings in Japan. A relationship between the degree of the thermal insulation of these houses and corresponding rates of improvement in the following 10 diseases were formulated: heart disease, cerebrovascular disease, hypertension, diabetes mellitus, asthma, dermatitis and eczema, pneumonia, inflammatory polyarthropathies, allergic rhinitis, and conjunctivitis. Following the statistical analysis of these outcomes, significant differences in improvement rates were identified among the levels of the thermal insulation of houses for the following five diseases: cerebrovascular diseases, asthma, dermatitis and eczema, allergic rhinitis, and conjunctivitis. In addition, the thermal environments of houses corresponding to each thermal insulation level were estimated by numerical simulations. Using these results, we organized the relationships between the thermal environment conditions of houses and observed prevalence rate for the following four diseases for which the improvement rates increased with increasing insulation levels and significant differences were identified: asthma, dermatitis and eczema, allergic rhinitis, and conjunctivitis. Consequently, we formulated equations to predict the prevalence rates of these diseases using the "mean operative temperature of rooms occupied by each family member from January 1 to February 28."

Thermal transport of confined water molecules in quasi-one-dimensional nanotubes.

Dimensions and molecular structures play pivotal roles in the principle of heat conduction. The dimensional characteristics of a solution within nanoscale systems depend on the degrees of confinement. However, the influence of such variations on heat transfer remains inadequately understood. Here, we perform quasi-one-dimensional non-equilibrium molecular dynamics simulations to calculate the thermal conductivity of water molecules confined in carbon nanotubes. The structure of water molecules is determined depending on the nanotube radius, forming a single-file, a single-layer, and a double-layer structure, corresponding to an increasing radius order. We reveal that the thermal conductivity of liquid water has a sublinear dependency on nanotube length exclusively when water molecules form a single file. A stronger confinement leads to behavioral and structural characteristics closely resembling a one-dimensional nature. Moreover, single-layer-structured water molecules exhibit enhanced thermal conductivity. We elucidate that this is due to the increase in the local water density and the absence of transitions to another layer, which typically occurs in systems with double-layer water structures within relatively large radius nanotubes.

Errors in the Calculation of the Population Attributable Fraction.

One of the common errors in the calculation of the population attributable fraction (PAF) is the use of an adjusted risk ratio in the Levin formula. In this article, we discuss the errors visually using wireframes by varying the standardized mortality ratio (SMR) and associational risk ratio (aRR) when the prevalence of exposure is fixed. When SMR >1 and SMR > aRR, the absolute bias is positive, and its magnitude increases as the difference between SMR and aRR increases. By contrast, when aRR > SMR > 1, the absolute bias is negative and its magnitude is relatively small. Moreover, when SMR > aRR, the relative bias is larger than one, whereas when SMR < aRR, the relative bias is smaller than one. Although the target population of the PAF is the total population, the target of causation of the PAF is not the total population but the exposed group.

Cytonuclear interactions modulate the plasticity of photosynthetic rhythmicity and growth in wild barley.

In plants, the contribution of the plasmotype (mitochondria and chloroplast) in controlling the circadian clock plasticity and possible consequences on cytonuclear genetic makeup have yet to be fully elucidated. A genome-wide association study in the wild barley (Hordeum vulgare ssp. spontaneum) B1K collection identified overlap with our previously mapped DRIVERS OF CLOCKS (DOCs) loci in wild-cultivated interspecific population. Moreover, we identified non-random segregation and epistatic interactions between nuclear DOCs loci and the chloroplastic RpoC1 gene, indicating an adaptive value for specific cytonuclear gene combinations. Furthermore, we show that DOC1.1, which harbours the candidate SIGMA FACTOR-B (SIG-B) gene, is linked with the differential expression of SIG-B and CCA1 genes and contributes to the circadian gating response to heat. High-resolution temporal growth and photosynthesis measurements of B1K also link the DOCs loci to differential growth, Chl content and quantum yield. To validate the involvement of the Plastid encoded polymerase (PEP) complex, we over-expressed the two barley chloroplastic RpoC1 alleles in Arabidopsis and identified significant differential plasticity under elevated temperatures. Finally, enhanced clock plasticity of de novo ENU (N-Ethyl-N-nitrosourea) -induced barley rpoB1 mutant further implicates the PEP complex as a key player in regulating the circadian clock output. Overall, this study highlights the contribution of specific cytonuclear interaction between rpoC1 (PEP gene) and SIG-B with distinct circadian timing regulation under heat, and their pleiotropic effects on growth implicate an adaptive value.

Development of 12 sets of chromosome segment substitution lines that enhance allele mining in Asian cultivated rice.

Many agronomic traits that are important in rice breeding are controlled by multiple genes. The extensive time and effort devoted so far to identifying and selecting such genes are still not enough to target multiple agronomic traits in practical breeding in Japan because of a lack of suitable plant materials in which to efficiently detect and validate beneficial alleles from diverse genetic resources. To facilitate the comprehensive analysis of genetic variation in agronomic traits among Asian cultivated rice, we developed 12 sets of chromosome segment substitution lines (CSSLs) with the japonica background, 11 of them in the same genetic background, using donors representing the genetic diversity of Asian cultivated rice. Using these materials, we overviewed the chromosomal locations of 1079 putative QTLs for seven agronomic traits and their allelic distribution in Asian cultivated rice through multiple linear regression analysis. The CSSLs will allow the effects of putative QTLs in the highly homogeneous japonica background to be validated.

Mistaken information can lead only to misguided conclusions and policies: a commentary regarding Schüz et al.'s response.

BACKGROUND: After reviewing selected scientific evidence, Schüz et al. made two recommendations in the 2018 International Agency for Research on Cancer (IARC) Technical Publication No. 46. Their first recommendation was against population thyroid screening after a nuclear accident, and the second was that consideration be given to offering a long-term thyroid monitoring program for higher-risk individuals (100-500 mGy or more radiation) after a nuclear accident. However, their review of the scientific evidence was inadequate and misrepresented the information from both Chernobyl and Fukushima. We wrote a review article published in Environmental Health in 2022 using the "Toolkit for detecting misused epidemiological methods." Schüz et al. critiqued our 2022 review article in 2023; their critique, based also on their 2018 IARC Technical Publication No. 46, was so fraught with problems that we developed this response. MAIN BODY: Schüz et al. suggest that hundreds of thyroid cancer cases in children and adolescents, detected through population thyroid examinations using ultrasound echo and conducted since October 2011 in Fukushima, were not caused by the 2011 Fukushima Daiichi Nuclear Power Plant accident. Schüz et al. compared thyroid cancers in Fukushima directly with those in Chernobyl after April 1986 and listed up to five reasons to deny a causal relationship between radiation and thyroid cancers in Fukushima; however, those reasons we dismiss based on available evidence. No new scientific evidence was presented in their response to our commentary in which we pointed out that misinformation and biased scientific evidence had formed the basis of their arguments. Their published article provided erroneous information on Fukushima. The article implied overdiagnosis in adults and suggested that overdiagnosis would apply to current Fukushima cases. The IARC report did not validate the secondary confirmatory examination in the program which obscures the fact that overdiagnosis may not have occurred as much in Fukushima. The report consequently precluded the provision of important information and measures. CONCLUSION: Information provided in the IARC Technical Publication No. 46 was based on selected scientific evidence resulting in both public and policy-maker confusion regarding past and present nuclear accidents, especially in Japan. It should be withdrawn.

Integrated genome-wide differentiation and association analyses identify causal genes underlying breeding-selected grain quality traits in japonica rice.

Improving grain quality is a primary objective in contemporary rice breeding. Japanese modern rice breeding has developed two different types of rice, eating and sake-brewing rice, with different grain characteristics, indicating the selection of variant gene alleles during the breeding process. Given the critical importance of promptly and efficiently identifying genes selected in past breeding for future molecular breeding, we conducted genome scans for divergence, genome-wide association studies, and map-based cloning. Consequently, we successfully identified two genes, OsMnS and OsWOX9D, both contributing to rice grain traits. OsMnS encodes a mannan synthase that increases the white core frequency in the endosperm, a desirable trait for sake brewing but decreases the grain appearance quality. OsWOX9D encodes a grass-specific homeobox-containing transcription factor, which enhances grain width for better sake brewing. Furthermore, haplotype analysis revealed that their defective alleles were selected in East Asia, but not Europe, during modern improvement. In addition, our analyses indicate that a reduction in grain mannan content during African rice domestication may also be caused a defective OsMnS allele due to breeding selection. This study not only reveals the delicate balance between grain appearance quality and nutrition in rice but also provides a new strategy for isolating causal genes underlying complex traits, based on the concept of "breeding-assisted genomics" in plants.

Heterogeneous biological membranes regulate protein partitioning via fluctuating diffusivity.

Cell membranes phase separate into ordered Lo and disordered Ld domains depending on their compositions. This membrane compartmentalization is heterogeneous and regulates the localization of specific proteins related to cell signaling and trafficking. However, it is unclear how the heterogeneity of the membranes affects the diffusion and localization of proteins in Lo and Ld domains. Here, using Langevin dynamics simulations coupled with the phase-field (LDPF) method, we investigate several tens of milliseconds-scale diffusion and localization of proteins in heterogeneous biological membrane models showing phase separation into Lo and Ld domains. The diffusivity of proteins exhibits temporal fluctuations depending on the field composition. Increases in molecular concentrations and domain preference of the molecule induce subdiffusive behavior due to molecular collisions by crowding and confinement effects, respectively. Moreover, we quantitatively demonstrate that the protein partitioning into the Lo domain is determined by the difference in molecular diffusivity between domains, molecular preference of domain, and molecular concentration. These results pave the way for understanding how biological reactions caused by molecular partitioning may be controlled in heterogeneous media. Moreover, the methodology proposed here is applicable not only to biological membrane systems but also to the study of diffusion and localization phenomena of molecules in various heterogeneous systems.

A new strategy to exploit maximum rate performance for aqueous batteries through a judicious selection of MOF-type electrodes.

A metal-organic framework (MOF) having a redox active 1,4,5,8-naphthalenetetracarboxdiimide (NDI) derivative in its organic linker shows excellent rate performance as an electrode material for aqueous batteries thanks to its large pores. Among aqueous electrolytes examined, K+-based ones exhibit the highest rate performance, which is caused by the highest mobility of the smallest hydrated K+ ion not only in the aqueous electrolyte but also in the electrode. Since the use of a counter electrode with insufficiently small pores for the full-cell configuration offsets this merit, our study may lead to a conclusion that the maximum rate performance for aqueous batteries will be accomplished only through further elaboration of both electrode materials with sufficiently large pores, in which hydrated ions can travel equally fast as those in the electrolyte.

Supported Noble Metal Catalysts and Adsorbents with Soft Lewis Acid Functions.

Heterogeneous noble metal catalysts exhibit various functions. Although their redox functions have been extensively studied, we focused on their soft Lewis acid functions. Supported Au, Pt, and Pd catalysts electrophilically attack the π-electrons of soft bases such as alkynes, alkenes, and aromatic compounds to perform addition and substitution reactions. Hydroamination, intramolecular cyclization of alkynyl carboxylic acids, isomerization of allylic esters, vinyl exchange reactions, Wacker oxidation, and oxidative homocoupling of aromatics are introduced based on a discussion of the active species and reaction mechanisms. Furthermore, the adsorption of sulfur compounds, which are soft bases, onto the supported AuNPs is discussed. The adsorption and removal of 1,3-dimethyltrisulfane (DMTS), which is the compound responsible for the stale odor of "hine-ka" in alcoholic beverages, particularly Japanese sake, is described.

Wetting hysteresis induces effective unidirectional water transport through a fluctuating nanochannel.

We propose a water pump that actively transports water molecules through nanochannels. Spatially asymmetric noise fluctuations imposed on the channel radius cause unidirectional water flow without osmotic pressure, which can be attributed to hysteresis in the cyclic transition between the wetting/drying states. We show that the water transport depends on fluctuations, such as white, Brownian, and pink noises. Because of the high-frequency components in white noise, fast switching of open and closed states inhibits channel wetting. Conversely, pink and Brownian noises generate high-pass filtered net flow. Brownian fluctuation leads to a faster water transport rate, whereas pink noise has a higher capability to overcome pressure differences in the opposite direction. A trade-off relationship exists between the resonant frequency of the fluctuation and the flow amplification. The proposed pump can be considered as an analogy for the reversed Carnot cycle, which is the upper limit of the energy conversion efficiency.

MORE PANICLES 3, a natural allele of OsTB1/FC1, impacts rice yield in paddy fields at elevated CO2 levels.

Improving crop yield potential through an enhanced response to rising atmospheric CO2 levels is an effective strategy for sustainable crop production in the face of climate change. Large-sized panicles (containing many spikelets per panicle) have been a recent ideal plant architecture (IPA) for high-yield rice breeding. However, few breeding programs have proposed an IPA under the projected climate change. Here, we demonstrate through the cloning of the rice (Oryza sativa) quantitative trait locus for MORE PANICLES 3 (MP3) that the improvement in panicle number increases grain yield at elevated atmospheric CO2 levels. MP3 is a natural allele of OsTB1/FC1, previously reported as a negative regulator of tiller bud outgrowth. The temperate japonica allele advanced the developmental process in axillary buds, moderately promoted tillering, and increased the panicle number without negative effects on the panicle size or culm thickness in a high-yielding indica cultivar with large-sized panicles. The MP3 allele, containing three exonic polymorphisms, was observed in most accessions in the temperate japonica subgroups but was rarely observed in the indica subgroup. No selective sweep at MP3 in either the temperate japonica or indica subgroups suggested that MP3 has not been involved and utilized in artificial selection during domestication or breeding. A free-air CO2 enrichment experiment revealed a clear increase of grain yield associated with the temperate japonica allele at elevated atmospheric CO2 levels. Our findings show that the moderately increased panicle number combined with large-sized panicles using MP3 could be a novel IPA and contribute to an increase in rice production under climate change with rising atmospheric CO2 levels.

Theoretical Mechanistic Investigation of the Dynamic Kinetic Resolution of N-Protected Amino Acid Esters using Phase-Transfer Catalysts.

A detailed theoretical mechanistic investigation on the dynamic kinetic resolution of N-protected amino acid esters using phase-transfer catalysts is described. Semiautomatic exhaustive conformation search of transition state (TS)-like structures were carried out using the ConFinder program and the pseudo-TS conformational search (PTSCS) method. This conformational search method successfully provided reasonable TS structures for determining the stereoselectivity in the asymmetric base hydrolysis of hexafluoroisopropyl (HFIP) esters as well as the racemization mechanism. Furthermore, the independent gradient model (IGM) analysis of the TS structures suggested that the H-bonding interactions with the oxyanion hole and π-stacking interactions are the common important features of the proposed TS structures that determine the stereoselectivity.

Independent control of organ number and distribution pattern in rice panicle.

As the determinants of yield products, rice panicle traits are important targets for breeding. Despite their importance in grain filling and subsequent yield productivity, knowledge on the organ distribution pattern in rice panicles is limited owing to the lack of objective evaluation methods. In this study, we developed a method for quantifying rice panicle organ distribution patterns. To validate our method for practical application in biology, we integrated this method into a quantitative trait locus (QTL) analysis and identified QTLs for panicle organ distribution patterns in rice. Interestingly, Grain number 1 (Gn1), a major QTL of organ number, was not identified as a QTL for distribution pattern, indicating that the number and distribution of panicle organs are independently controlled. This study provides insight into rice panicle organ distribution patterns that will help improve breeding targeting rice panicle architecture.

Tunable pheromone interactions among microswimmers.

Indirect interactions via shared memory deposited on the field ("field memory") play an essential role in collective motions. Some motile species, such as ants and bacteria, use attractive pheromones to complete many tasks. Mimicking these kinds of collective behavior at the laboratory scale, we present a pheromone-based autonomous agent system with tunable interactions. In this system, colloidal particles leave phase-change trails reminiscent of the process of pheromone deposition by individual ants, and the trails attract other particles and themselves. To implement this, we combine two physical phenomena: the phase change of a Ge2Sb2Te5 (GST) substrate by self-propelled Janus particles (pheromone deposition) and the AC (alternating current) electroosmotic (ACEO) flow generated by this phase change (pheromone attraction). Laser irradiation causes the GST layer to crystalize locally beneath the Janus particles, owing to the lens heating effect. Under AC field application, the high conductivity of the crystalline trail causes a field concentration and generates ACEO flow, and we introduce this flow as an attractive interaction between the Janus particles and the crystalline trail. By changing the AC frequency and voltage, we can tune the attractive flow, i.e., the sensitivity of the Janus particles to the trail, and the isolated particles undergo diverse states of motion, from self-caging to directional motion. A swarm of Janus particles also shows different states of collective motion, including colony formation and line formation. This tunability enables a reconfigurable system driven by a pheromone-like memory field.

Effective use of legacy data in a genome-wide association studies improves the credibility of quantitative trait loci detection in rice.

Genome-wide association studies (GWASs) are used to detect quantitative trait loci (QTL) using genomic and phenotypic data as inputs. While genomic data are obtained with high throughput and low cost, obtaining phenotypic data requires a large amount of effort and time. In past breeding programs, researchers and breeders have conducted a large number of phenotypic surveys and accumulated results as legacy data. In this study, we conducted a GWAS using phenotypic data of temperate japonica rice (Oryza sativa) varieties from a public database. The GWAS using the legacy data detected several known agriculturally important genes, indicating reliability of the legacy data for GWAS. By comparing the GWAS using legacy data (L-GWAS) and a GWAS using phenotypic data that we measured (M-GWAS), we detected reliable QTL for agronomically important traits. These results suggest that an L-GWAS is a strong alternative to replicate tests to confirm the reproducibility of QTL detected by an M-GWAS. In addition, because legacy data have often been accumulated for many traits, it is possible to evaluate the pleiotropic effect of the QTL identified for the specific trait that we focused on with respect to various other traits. This study demonstrates the effectiveness of using legacy data for GWASs and proposes the use of legacy data to accelerate genomic breeding.

Exchangeability of Measures of Association Before and After Exposure Status Is Flipped: Its Relationship With Confounding in the Counterfactual Model.

BACKGROUND: The counterfactual definition of confounding is often explained in the context of exchangeability between the exposed and unexposed groups. One recent approach is to examine whether the measures of association (eg, associational risk difference) are exchangeable when exposure status is flipped in the population of interest. We discuss the meaning and utility of this approach, showing their relationships with the concept of confounding in the counterfactual framework. METHODS: Three hypothetical cohort studies are used, in which the target population is the total population. After providing an overview of the notions of confounding in distribution and in measure, we discuss the approach from the perspective of exchangeability of measures of association (eg, factual associational risk difference vs counterfactual associational risk difference). RESULTS: In general, if the measures of association are non-exchangeable when exposure status is flipped, confounding in distribution is always present, although confounding in measure may or may not be present. Even if the measures of association are exchangeable when exposure status is flipped, there could be confounding both in distribution and in measure. When we use risk difference or risk ratio as a measure of interest and the exposure prevalence in the population is 0.5, testing the exchangeability of measures of association is equivalent to testing the absence of confounding in the corresponding measures. CONCLUSION: The approach based on exchangeability of measures of association essentially does not provide a definition of confounding in the counterfactual framework. Subtly differing notions of confounding should be distinguished carefully.

A gynandromorph of the stonefly Amphinemura zonata (Okamoto, 1922) (Plecoptera: Nemouridae) from Japan.

A gynandromorph of Amphinemura zonata (Okamoto, 1922) collected from Matsubara-izumi Pond in Japan is described and illustrated as the first report in the genus. The specimen exhibits bilateral gynandromorphism on abdominal sterna 79 and the paraprocts. Male features occur on the right half and female features on the left half. In addition, the gynandromorph is predominantly female as it retains female features on the dorsal male half of the abdomen, has eggs in the abdomen, has female-length fore wings, and lacks main male features such as an epiproct and a hypoproct on sternum 9.