Genomic and transcriptomic analyses of the subterranean termite Reticulitermes speratus: Gene duplication facilitates social evolution.

Termites are model social organisms characterized by a polyphenic caste system. Subterranean termites (Rhinotermitidae) are ecologically and economically important species, including acting as destructive pests. Rhinotermitidae occupies an important evolutionary position within the clade representing a transitional taxon between the higher (Termitidae) and lower (other families) termites. Here, we report the genome, transcriptome, and methylome of the Japanese subterranean termite Reticulitermes speratus Our analyses highlight the significance of gene duplication in social evolution in this termite. Gene duplication associated with caste-biased gene expression was prevalent in the R. speratus genome. The duplicated genes comprised diverse categories related to social functions, including lipocalins (chemical communication), cellulases (wood digestion and social interaction), lysozymes (social immunity), geranylgeranyl diphosphate synthase (social defense), and a novel class of termite lineage-specific genes with unknown functions. Paralogous genes were often observed in tandem in the genome, but their expression patterns were highly variable, exhibiting caste biases. Some of the assayed duplicated genes were expressed in caste-specific organs, such as the accessory glands of the queen ovary and the frontal glands of soldier heads. We propose that gene duplication facilitates social evolution through regulatory diversification, leading to caste-biased expression and subfunctionalization and/or neofunctionalization conferring caste-specialized functions.

Development of the Pronotal Explanate Margin, a Novel Evolutionary Trait in Tortoise Beetles.

Most tortoise beetles, belonging to the subfamily Cassidinae (Coleoptera: Chrysomelidae), possess distinctive explanate margins, comprising elongations of the pronotum and elytra outer margins. These margins flatten against the ground, serving as a unique defensive mechanism against predators. To understand the developmental and evolutionary origins of explanate margins, we examined the development of the pronotal part of these structures in two tortoise beetle species: Thlaspida biramosa (Boheman) (tribe Cassidini) and Laccoptera nepalensis (Boheman) (tribe Aspidimorphini). Although final (fifth) instar larvae of both species exhibited no external prothoracic structures associated with explanate margins, pupae possessed a plate-shaped structure projecting anterolaterally on their pronotum. This plate-shaped structure was identified as the pupal primordium of the pronotal explanate margin, as the explanate margin emerged from inside the structure during eclosion. In prepupae of T. biramosa, the primordial tissue exhibited three region-specific folding and furrowing patterns, beneath larval cuticles. These epithelial structures expanded within minutes at the onset of pupation, resulting in pupal primordial formation. Thus, pronotal explanate margins originate from pronotal epithelia, with the furrowing and folding patterns of the epithelia shaping pupal and even adult pronotal explanate margins. The presence of morphologically similar pupal pronotal projections in various Cassidinae suggests that the development of pronotal explanate margins is likely common in these beetles.

Annual change in eGFR in renal hypouricemia: a retrospective pilot study.

BACKGROUND: Extremely low uric acid (UA) levels or increased urinary UA (Uua) excretion might be risk factors for kidney disease in renal hypouricemia (RHU) patients, but their relationship with kidney dysfunction is unclear. This study investigated time-dependent changes in eGFR in RHU patients. METHODS: This multicenter retrospective study assessed UA metabolism and changes in eGFR (median 5.5 years) in 13 RHU patients. We then compared eGFR change in 7 of 13 RHU patients whose eGFR could be measured for 4 years with those in normouricemic group (n = 31). In addition, 7 RHU patients were divided into two groups based on URAT1 gene mutations: homozygote and compound heterozygote mutations (Homo/Com group, n = 3), and wild-type and heterogeneous mutations (WT/Hetero group, n = 4). RESULTS: In 13 RHU patients, the median and mean serum UA (SUA) were 0.8 (0.4-2.5) and 1.1 ± 0.7 mg/dL. The median and mean Uua were 44.3 (12.7-141.1) and 49.7 ± 36.2 mg/dL. The median and mean urinary urate clearance (Cua/Ccr) were 46.8 (11.3-73.6) and 43.3 ± 19.7%. Over 4 years, eGFR did not change in the RHU group but declined in the normouricemic group. Annual mean eGFR decline and change rate in the RHU group were the same as those in the normouricemic group (- 1.09 ± 1.11 vs. - 1.09 ± 1.92 mL/min/1.73 m2/year, p = 0.996) (- 1.74 ± 1.96 vs. - 1.36 ± 2.10%, p = 0.664). And no significant difference was found in eGFR decline or change rate between Homo/Com and WT/Hetero groups (- 0.33 ± 1.03 vs. - 1.67 ± 0.85 mL/min/1.73 m2/year, p = 0.116) (- 0.61 ± 1.62 vs. - 2.59 ± 1.91%, p = 0.210). CONCLUSION: RHU from URAT1 genetic mutation may not show eGFR decline over 4 consecutive years.

A hybrid type Ia supernova with an early flash triggered by helium-shell detonation.

Type Ia supernovae arise from the thermonuclear explosion of white-dwarf stars that have cores of carbon and oxygen. The uniformity of their light curves makes these supernovae powerful cosmological distance indicators, but there have long been debates about exactly how their explosion is triggered and what kind of companion stars are involved. For example, the recent detection of the early ultraviolet pulse of a peculiar, subluminous type Ia supernova has been claimed as evidence for an interaction between a red-giant or a main-sequence companion and ejecta from a white-dwarf explosion. Here we report observations of a prominent but red optical flash that appears about half a day after the explosion of a type Ia supernova. This supernova shows hybrid features of different supernova subclasses, namely a light curve that is typical of normal-brightness supernovae, but with strong titanium absorption, which is commonly seen in the spectra of subluminous ones. We argue that this early flash does not occur through previously suggested mechanisms such as the companion-ejecta interaction. Instead, our simulations show that it could occur through detonation of a thin helium shell either on a near-Chandrasekhar-mass white dwarf, or on a sub-Chandrasekhar-mass white dwarf merging with a less-massive white dwarf. Our finding provides evidence that one branch of previously proposed explosion models-the helium-ignition branch-does exist in nature, and that such a model may account for the explosions of white dwarfs in a mass range wider than previously supposed.

First Identification of a CMB Lensing Signal Produced by 1.5 Million Galaxies at z∼4: Constraints on Matter Density Fluctuations at High Redshift.

We report the first detection of the dark matter distribution around Lyman break galaxies (LBGs) at high redshift through the cosmic microwave background (CMB) lensing measurements with the public Planck PR3 κ map. The LBG sample consists of 1 473 106 objects with the median redshift of z∼4 that are identified in a total area of 305 deg^{2} observed by the Hyper Suprime-Cam Strategic Survey Program survey. After careful investigations of systematic uncertainties, such as contamination from foreground galaxies and cosmic infrared background, we obtain the significant detection of the CMB lensing signal at 5.1σ that is dominated by 2-halo term signals of the LBGs. Fitting a simple model consisting of the Navarro-Frenk-White profile and the linear-bias model, we obtain the typical halo mass of M_{h}=2.9_{-2.5}^{+9.5}×10^{11} h^{-1} M_{⊙}. Combining the CMB lensing and galaxy-galaxy clustering signals on the large scales, we demonstrate the first cosmological analysis at z∼4 that constrains (Ω_{m0},σ_{8}). We find that our constraint on σ_{8} is roughly consistent with the Planck cosmology, while this σ_{8} constraint is lower than the Planck cosmology over the 1σ level. This study opens up a new window for constraining cosmological parameters at high redshift by the combination of CMB and high-z galaxies, as well as studying the interplay between galaxy evolution and large-scale structure at such high redshift, by upcoming CMB and optical and near-infrared imaging surveys.

Geographic patterns in colonial reproductive strategy in Myrmecina nipponica: Links between biogeography and a key polymorphism in ants.

The ability to express different phenotypes can help define species distributions by allowing access to, and exploitation of, new environments. Social insects employ two markedly different reproductive strategies with contrasting cost/benefit characteristics: independent colony foundation (ICF), which is associated with high dispersal range and high risk, and dependent colony foundation (DCF), characterized by low risk but low dispersal. The ant Myrmecina nipponica employs both of these strategies, with the frequency of each apparently varying between populations. We combine molecular data with data on reproductive strategy from different populations of this species throughout Japan to explore how this polymorphism is linked to environmental factors and whether this relationship can help explain the current and historical biogeography of this species. Reproductive strategy exhibited a strong geographic pattern, with ICF predominant in southern populations and DCF more common in northern and southern highland populations. Molecular analyses clearly divided populations into broad geographic regions, with the southern lowland populations basal to (southern highland (+ northern)) populations. Intra-population polymorphism in colony-founding strategy was widespread, and polymorphism was reconstructed as the likely ancestral state. The frequency of different strategies was linked with climate, with DCF more common in colder areas. A recent inferred origin to the northern lineage suggests that colonization of northern Japan was a rapid event coincident with warming at the end of the Last Glacial Maxima, likely facilitated by the cold-adaptive advantages of DCF. We discuss how such polymorphisms could help explain the biogeography of this and other social insects.

A lipocalin protein, Neural Lazarillo, is key to social interactions that promote termite soldier differentiation.

Social communication among castes is a crucial component of insect societies. However, the genes involved in soldier determination through the regulation of inter-individual interactions are largely unknown. In an incipient colony of the damp-wood termite Zootermopsis nevadensis, the first larva to develop into a third instar always differentiates into a soldier via frequent trophallactic feeding from the reproductives. Here, by performing RNA-seq analysis of third instar larvae, a homologue of Neural Lazarillo (named ZnNLaz1) was found to be the most differentially expressed gene in these soldier-destined larvae, compared with worker-destined larvae. This gene encodes a lipocalin protein related to the transport of small hydrophobic molecules. RNAi-induced knockdown of ZnNLaz1 significantly inhibited trophallactic interactions with the queen and decreased the soldier differentiation rates. This protein is localized in the gut, particularly in the internal wall, of soldier-destined larvae, suggesting that it is involved in the integration of social signals from the queen through frequent trophallactic behaviours. Based on molecular phylogenetic analysis, we suggest that a novel function of termite NLaz1 has contributed to social evolution from the cockroach ancestors of termites. These results indicated that a high larval NLaz1 expression is crucial for soldier determination through social communication in termites.

SRSF1-3 contributes to diversification of the immunoglobulin variable region gene by promoting accumulation of AID in the nucleus.

Activation-induced cytidine deaminase (AID) is essential for diversification of the Ig variable region (IgV). AID is excluded from the nucleus, where it normally functions. However, the molecular mechanisms responsible for regulating AID localization remain to be elucidated. The SR-protein splicing factor SRSF1 is a nucleocytoplasmic shuttling protein, a splicing isoform of which called SRSF1-3, has previously been shown to contribute to IgV diversification in chicken DT40 cells. In this study, we examined whether SRSF1-3 functions in IgV diversification by promoting nuclear localization of AID. AID expressed alone was localized predominantly in the cytoplasm. In contrast, co-expression of AID with SRSF1-3 led to the nuclear accumulation of both AID and SRSF1-3 and the formation of a protein complex that contained them both, although SRSF1-3 was dispensable for nuclear import of AID. Expression of either SRSF1-3 or a C-terminally-truncated AID mutant increased IgV diversification in DT40 cells. However, overexpression of exogenous SRSF1-3 was unable to further enhance IgV diversification in DT40 cells expressing the truncated AID mutant, although SRSF1-3 was able to form a protein complex with the AID mutant. These results suggest that SRSF1-3 promotes nuclear localization of AID probably by forming a nuclear protein complex, which might stabilize nuclear AID and induce IgV diversification in an AID C-terminus-dependent manner.

Social dominance and reproductive differentiation mediated by dopaminergic signaling in a queenless ant.

In social Hymenoptera with no morphological caste, a dominant female becomes an egg layer, whereas subordinates become sterile helpers. The physiological mechanism that links dominance rank and fecundity is an essential part of the emergence of sterile females, which reflects the primitive phase of eusociality. Recent studies suggest that brain biogenic amines are correlated with the ranks in dominance hierarchy. However, the actual causality between aminergic systems and phenotype (i.e. fecundity and aggressiveness) is largely unknown due to the pleiotropic functions of amines (e.g. age-dependent polyethism) and the scarcity of manipulation experiments. To clarify the causality among dominance ranks, amine levels and phenotypes, we examined the dynamics of the aminergic system during the ontogeny of dominance hierarchy in the queenless ant Diacamma sp., which undergoes rapid physiological differentiation based on dominance interactions. Brain dopamine levels differed between dominants and subordinates at day 7 after eclosion, although they did not differ at day 1, reflecting fecundity but not aggressiveness. Topical applications of dopamine to the subordinate workers induced oocyte growth but did not induce aggressiveness, suggesting the gonadotropic effect of dopamine. Additionally, dopamine receptor transcripts (dopr1 and dopr2) were elevated in the gaster fat body of dominant females, suggesting that the fat body is a potential target of neurohormonal dopamine. Based on this evidence, we suggest that brain dopamine levels are elevated in dominants as a result of hierarchy formation, and differences in dopamine levels cause the reproductive differentiation, probably via stimulation of the fat body.

Intracolonial genetic variation affects reproductive skew and colony productivity during colony foundation in a parthenogenetic termite.

BACKGROUND: In insect societies, intracolonial genetic variation is predicted to affect both colony efficiency and reproductive skew. However, because the effects of genetic variation on these two colony characteristics have been tested independently, it remains unclear whether they are affected by genetic variation independently or in a related manner. Here we test the effect of genetic variation on colony efficiency and reproductive skew in a rhinotermitid termite, Reticulitermes speratus, a species in which female-female pairs can facultatively found colonies. We established colonies using two types of female-female pairs: colonies founded by sisters (i.e., sister-pair colonies) and those founded by females from different colonies (i.e., unrelated-pair colonies). Colony growth and reproductive skew were then compared between the two types of incipient colonies. RESULTS: At 15 months after colony foundation, unrelated-pair colonies were larger than sister-pair colonies, although the caste ratio between workers and nymphs, which were alternatively differentiated from young larvae, did not differ significantly. Microsatellite DNA analyses of both founders and their parthenogenetically produced offspring indicated that, in both sister-pair and unrelated-pair colonies, there was no significant skew in the production of eggs, larvae, workers and soldiers. Nymph production, however, was significantly more skewed in the sister-pair colonies than in unrelated-pair colonies. Because nymphs can develop into winged adults (alates) or nymphoid reproductives, they have a higher chance of direct reproduction than workers in this species. CONCLUSIONS: Our results support the idea that higher genetic variation among colony members could provide an increase in colony productivity, as shown in hymenopteran social insects. Moreover, this study suggests that low genetic variation (high relatedness) between founding females increases reproductive skew via one female preferentially channeling her relatives along the reproductive track. This study thus demonstrated that, in social insects, intracolonial genetic variation can simultaneously affect both colony efficiency and reproductive skew.

A comparative study on the effectiveness of losartan/hydrochlorothiazide and telmisartan/hydrochlorothiazide in patients with hypertension.

PURPOSE: Long-term effects of a low-dose hydrochlorothiazide (HCTZ) with losartan (LOS) on uric acid (UA) metabolism as well as glucose metabolism have been studied in hypertensive patients in comparison with those of a low-dose HCTZ with telmisartan (TEL). METHOD: Fifty-nine hypertensive patients were allocated to a combination therapy with either losartan (50 mg/day)/HCTZ (12.5 mg/day) (LOS + HCTZ group: n = 37) or telmisartan (40 mg/day)/HCTZ (12.5 mg/day) (TEL + HCTZ group: n = 22), respectively. Before and 1 year after the treatment, blood pressure and biochemical parameters of blood and urine were evaluated. RESULTS: Both systolic and diastolic blood pressures significantly decreased in two groups, without any statistical differences among them. LOS + HCTZ caused no changes in the serum UA level or the ratio of UA clearance to creatinine clearance (CUA/Ccr), whereas TEL + HCTZ significantly increased the serum UA level and reduced CUA/Ccr. LOS + HCTZ did not influence CUA/Ccr in patients with their serum UA below 5.4 mg/dl, while LOS + HCTZ significantly increased CUA/Ccr in patients with their serum UA above 5.5 mg/dl. TEL + HCTZ significantly reduced CUA/Ccr in patients with their serum UA below and above 5.4 mg/dl to increase serum UA level significantly. Neither combination therapies caused any changes in fasting plasma glucose, HbA1c and HOMA-R. In patients with their serum UA level above 5.4 mg/dl, TEL + HCTZ increased HOMA-R, whereas LOS + HCTZ did not. CONCLUSIONS: LOS + HCTZ did not influence UA metabolism as well as glucose metabolism, likely because of inhibitory action of losartan on URAT1, although TEL + HCTZ were accompanied with impairment of the UA metabolism and glucose metabolism.

Effects of azelnidipine on uric acid metabolism in patients with essential hypertension.

PURPOSE: To examine effects of a long-acting calcium channel blocker (CCB) azelnidipine on uric acid metabolism in hypertensive patients. METHODS: Azelnidipine was administered to 72 patients at a daily dose of 8 mg or 16 mg. In 22 cases out of the 72 patients, a different CCB was switched to azelnidipine. Blood pressure was measured and biochemical parameters of blood and urine were evaluated before and 2-3 months after the administration. RESULTS: Azelnidipine significantly decreased both systolic and diastolic blood pressure and the heart rate. It decreased both serum urate levels and the urinary uric acid to creatinine ratio (Uur/Ucr), but did not affect the uric acid clearance to creatinine clearance ratio (Cur/Ccr). Azelnidipine decreased both Uur/Ucr and Cur/Ccr in patients with Uur/Ucr ≥ 0.5 or ≥ 0.34, although it did not change these clearance parameters in patients with Uur/Ucr <0.5 or <0.34. Azelnidipine decreased the serum urate levels and Uur/Ucr in hyperuricemic patients with uric acid levels ≥ 7.0 mg/dL in males and ≥ 6.0 mg/dL in females. It did not change these parameters in normouricemic patients with serum urate levels <7.0 mg/dL in males and <6.0 mg/dL in females. Azelnidipine decreased Uur/Ucr and Cur/Ccr in hyperuricemic patients with normal or over excretion of uric acid, although it did not change these clearance parameters in hyperuricemic patients with uric acid hypoexcretion. CONCLUSIONS: Azelnidipine decreased the serum urate acid levels and Uur/Ucr, and this response was most prominent in hyperuricemic patients or patients with normal and over excretion of uric acid.

Evolution of the sex-determination gene Doublesex within the termite lineage.

The molecular mechanism of sex determination has long been considered conserved in insects. However, recent studies of hemimetabolous insects have challenged this notion. One notable example is termites. In Reticulitermes speratus, a homolog of sex determination gene, Doublesex (RsDsx), exhibits characteristics that are distinct from those of other insects, including sister-group cockroaches. It comprises a single exon, contains only doublesex/mab-3 DNA-binding domain (DM) but lacks a conserved oligomerization domain (OD), and exhibits transcriptional activity only in males. To investigate whether these characteristics are widespread within the termite lineage, we identified Dsx homologs in three different families. The absence of the conserved OD sequences was observed in all termite species examined, whereas the number of exons and expression patterns between sexes varied among families. Particularly, distinctive differences in Dsx were found in species from the Archotermopsidae and Kalotermitidae, both of which have a linear caste developmental pathway. Our findings indicate that diversification of Dsx structure and expression patterns may have contributed to ecological diversification, such as caste developmental pathways, within the termite lineage.

Candidate target genes of the male-specific expressed Doublesex in the termite Reticulitermes speratus.

Eusocial insects such as termites, ants, bees, and wasps exhibit a reproductive division of labor. The developmental regulation of reproductive organ (ovaries and testes) is crucial for distinguishing between reproductive and sterile castes. The development of reproductive organ in insects is regulated by sex-determination pathways. The sex determination gene Doublesex (Dsx), encoding transcription factors, plays an important role in this pathway. Therefore, clarifying the function of Dsx in the developmental regulation of sexual traits is important to understand the social evolution of eusocial insects. However, no studies have reported the function of Dsx in hemimetabolous eusocial group termites. In this study, we searched for binding sites and candidate target genes of Dsx in species with available genome information as the first step in clarifying the function of Dsx in termites. First, we focused on the Reticulitermes speratus genome and identified 101 candidate target genes of Dsx. Using a similar method, we obtained 112, 39, and 76 candidate Dsx target genes in Reticulitermes lucifugus, Coptotermes formosanus, and Macrotermes natalensis, respectively. Second, we compared the candidate Dsx target genes between species and identified 37 common genes between R. speratus and R. lucifugus. These included several genes probably involved in spermatogenesis and longevity. However, only a few common target genes were identified between R. speratus and the other two species. Finally, Dsx dsRNA injection resulted in the differential expression of several target genes, including piwi-like protein and B-box type zinc finger protein ncl-1 in R. speratus. These results provide valuable resource data for future functional analyses of Dsx in termites.

Prediction for Risk of Hypouricemia in Hospitalized Patients: A Single-center, Retrospective Cohort Study.

Background Hypouricemia, defined as a serum uric acid (SUA) level ≤2 mg/dL, could be a risk factor for death in hospitalized patients. However, how explanatory variables can explain hypouricemia as an objective variable in a logistic regression analysis remains unknown. Purpose To predict the risk factors for hypouricemia in hospitalized patients using a robust Bayesian logistic (RBL) model. Methods This study retrospectively enrolled patients who visited Yonago Medical Center between April 2020 and March 2021. The association between potential risk factors and hypouricemia was analyzed using the RBL model in Python-modulated PyMC3. The final model was selected based on the lowest Watanabe-Akaike information criterion (WAIC). Results Of the 618 patients, 64 (10.4%) had hypouricemia. Based on the model according to the lowest WAIC, independent risk factors for hypouricemia were febuxostat [odds ratio (OR) 5.46, 95% confidence interval (CI) 2.32-13.4], amino acids in parenteral nutrition (OR 5.19, 95% CI 1.62-15.1), TMP-SMX (OR 4.20, 95% CI 1.66-10.9), emaciation (OR 3.48, 95% CI 1.75-7.21), and serum sodium level (OR 0.90, 95% CI 0.84-0.96). Conclusion The RBL model predicted amino acids in parenteral nutrition, TMP-SMX, emaciation, and low serum sodium levels for hypouricemia, in addition to the authentic risk factor febuxostat.

Soldier morphogenesis in the damp-wood termite is regulated by the insulin signaling pathway.

Eusocial insects exhibit various morphological castes associated with the division of labor within a colony. Termite soldiers possess defensive traits including mandibles that are greatly exaggerated and enlarged, as compared to termite reproductives and workers. The enlarged mandibles of soldiers are known to result from dynamic morphogenesis during soldier differentiation that can be induced by juvenile hormone and its analogs. However, the detailed developmental mechanisms still remain unresolved. Because the insulin/insulin-like growth factor signaling (IIS) pathway has been shown to regulate the relative sizes of organs (i.e., allometry) in other insects, we examined the expression profiles of major IIS factors in the damp-wood termite Hodotermopsis sjostedti, during soldier differentiation. The relative expression patterns of orthologs for termite InR (HsjInR), PKB/Akt (HsjPKB/Akt), and FOXO (HsjFOXO) suggest that HsjInR and HsjPKB/Akt were up-regulated in the period of elongation of mandibles during soldier development. In situ hybridization showed that HsjInR was strongly expressed in the mandibular epithelial tissues, and RNA interference (RNAi) for HsjInR disrupted soldier-specific morphogenesis including mandibular elongation. These results suggest that signaling through the IIS pathway is required for soldier-specific morphogenesis. In addition, up-regulation of the IIS pathway in other body tissues occurred at earlier stages of development, indicating that there is tissue-specific IIS regulation. Because the IIS pathway is generally thought to act upstream of JH in insects, our results suggest the damp-wood termite may have evolved a novel feedback loop between JH and IIS that enables social interactions, rather than nutrition, to regulate caste determination.

Gross Appearances of the Posterior Cruciate Ligament Correlate With Its Histological Features but not With In Vivo Function in Cruciate-Retaining Total Knee Arthroplasty.

Background No study has evaluated whether the macroscopic appearance or histological features of the posterior cruciate ligament (PCL) affect the in vivo PCL function in cruciate-retaining (CR) total knee arthroplasty (TKA). The aim of this study is to elucidate the correlation between intraoperative gross appearances of the PCL and clinical parameters, their corresponding histological features, and the in vivo function. Methods The intraoperative gross appearances of the PCLs were evaluated; we also examined their correlations with clinical parameters, corresponding histological features, and the in vivo function in CR-TKA. Results There were significant correlations between intraoperative gross appearances of the PCL and that of the anterior cruciate ligament, the preoperative knee flexion angle, and the intercondylar notch stenosis. There was a significant correlation between the intraoperative gross appearance in the middle part and the corresponding histological features. However, there was no significant correlation between the intraoperative gross appearance or histological features and the PCL tension, amount of rollback, and maximum knee flexion angle. Conclusions The intraoperative gross appearance of the PCL correlated with clinical parameters. Also, there was a significant correlation between the intraoperative gross appearance in the middle part and the corresponding histological features; however, there was no correlation between the intraoperative gross appearance or histological features and the in vivo function.

Observing cosmic-ray extensive air showers with a silicon imaging detector.

Extensive air showers induced from high-energy cosmic rays provide a window into understanding the most energetic phenomena in the universe. We present a new method for observing these showers using the silicon imaging detector Subaru Hyper Suprime-Cam (HSC). This method has the advantage of being able to measure individual secondary particles. When paired with a surface detector array, silicon imaging detectors like Subaru HSC will be useful for studying the properties of extensive air showers in detail. The following report outlines the first results of observing extensive air showers with Subaru HSC. The potential for reconstructing the incident direction of primary cosmic rays is demonstrated and possible interdisciplinary applications are discussed.

Characterization of Urate Metabolism and Complications of Patients with Renal Hypouricemia.

Objective Both renal hypouricemia (RHU) and gout are associated with renal dysfunction and urolithiasis. The difference in renal complications associated with RHU and gout, however, has not been studied. We characterized the urate metabolism and complications of patients with RHU and compared them with patients with gout. Methods Eighteen patients with RHU who had a serum uric acid (SUA) level <2 mg/dL (10 men and 8 women), 44 patients with gout (44 men) and 16 normouricemic patients (4 men and 12 women) were included. The blood and urinary biochemical data were evaluated. A genetic analysis of uric acid transporter 1 (URAT1) was also conducted in 15 cases with RHU. Results The SUA level of RHU was 0.9±0.5/mg/dL, and the Uur/Ucr and Cur/Ccr were 0.56±0.14% and 45.7±18.0%, respectively. A genetic analysis of URAT1 in 15 RHU patients showed that 13 harbored a URAT1 gene mutation, whereas 2 harbored the wild-type gene. The SUA level was significantly lower in RHU patients (n=11) than in either gout patients (n=44) or normouricemic patients (n=16). This reduction was accompanied by the elevation of Cua/Ccr. Urinary beta 2-microglobulin levels were higher in RHU patients than in gout or normouricemia patients. Cua/Ccr correlated with normalized urinary beta 2-microglobulin levels. The prevalence of urolithiasis was 18.2% in RHU cases and 6.8% in gout cases. A homozygous URAT1 mutation was associated with urolithiasis. Conclusion Besides urolithiasis, RHU can be associated with tubular dysfunction, such as elevated urinary beta 2-microglobulin levels.

Effects of cilnidipine on serum uric acid level and urinary nitrogen monoxide excretion in patients with hypertension.

The effects of cilnidipine on the serum uric acid level and urinary NO excretion in hypertensive patients were investigated. Blood and urine samples of 16 hypertensive outpatients were collected before and 2 months after cilnidipine therapy (10 mg). The serum uric acid level decreased significantly after cilnidipine treatment, while the uric acid-creatinine clearance ratio was unaffected. The cilnidipine medication produced a significant increase in urinary NO excretion, although amlodipine did not change it significantly. Therefore, cilnidipine has a profound antihypertensive effect and may reduce the serum uric acid level and increase NO production in the kidney.