Striosomes Target Nigral Dopamine-Containing Neurons via Direct-D1 and Indirect-D2 Pathways Paralleling Classic Direct-Indirect Basal Ganglia Systems.

The classic output pathways of the basal ganglia are known as the direct-D1 and indirect-D2, or Go/No-Go, pathways. Balance of the activity in these canonical direct-indirect pathways is considered a core requirement for normal movement control, and their imbalance is a major etiologic factor in movement disorders including Parkinsons disease. We present evidence for a conceptually equivalent parallel system of direct-D1 and indirect-D2 pathways that arise from striatal projection neurons (SPNs) of the striosome compartment rather than from the matrix. These striosomal direct (S-D1) and indirect (S-D2) pathways, as a pair, target dopamine-containing neurons of the substantia nigra (SNpc) instead of the motor output nuclei of the basal ganglia. The novel anatomically and functionally distinct indirect-D2 striosomal pathway targets dopaminergic SNpc cells indirectly via a core region of the external pallidum (GPe). We demonstrate that these S-D1 and S-D2 pathways oppositely modulate striatal dopamine release in freely behaving mice under open-field conditions and oppositely modulate locomotor and other movements. These S-D1 and S-D2 pathways further exhibit different, time-dependent responses during performance of a probabilistic decision-making maze task and respond differently to rewarding and aversive stimuli. These contrasts depend on mediolateral and anteroposterior striatal locations of the SPNs as are the classic direct and indirect pathways. The effects of S-D1 and S-D2 stimulation on striatal dopamine release and voluntary locomotion are nearly opposite. The parallelism of the direct-indirect circuit design motifs of the striosomal S-D and S-D2 circuits and canonical matrix M-D1 and M-D2, and their contrasting behavioral effects, call for a major reformulation of the classic direct-indirect pathway model of basal ganglia function. Given that some striosomes receive limbic and association cortical inputs, the S-D1 and S-D2 circuits likely influence motivation for action and behavioral learning, complementing and possibly reorienting the motoric activities of the canonical matrix pathways. At a fundamental level, these findings suggest a unifying framework for aligning two sets of circuits that share the organizational motif of opponent D1 and D2 regulation, but that have different outputs and can even have opposite polarities in their targets and effects, albeit conditioned by striatal topography. Our findings further delineate a potentially therapeutically important set of pathways influencing dopamine, including a D2 receptor-linked S-D2 pathway likely unknowingly targeted by administration of many therapeutic drugs including those for Parkinsons disease. The novel parallel pathway model that we propose here could help to account for the normally integrated modulatory influence of the basal ganglia on motivation for actions as well as the actions themselves.

Developmental and adult striatal patterning of nociceptin ligand marks striosomal population with direct dopamine projections.

Circuit influences on the midbrain dopamine system are crucial to adaptive behavior and cognition. Recent developments in the study of neuropeptide systems have enabled high-resolution investigations of the intersection of neuromodulatory signals with basal ganglia circuitry, identifying the nociceptin/orphanin FQ (N/OFQ) endogenous opioid peptide system as a prospective regulator of striatal dopamine signaling. Using a prepronociceptin-Cre reporter mouse line, we characterized highly selective striosomal patterning of Pnoc mRNA expression in mouse dorsal striatum, reflecting early developmental expression of Pnoc . In the ventral striatum, Pnoc expression was was clustered across the nucleus accumbens core and medial shell, including in adult striatum. We found that Pnoc tdTomato reporter cells largely comprise a population of dopamine receptor D1 ( Drd1 ) expressing medium spiny projection neurons localized in dorsal striosomes, known to be unique among striatal projections neurons for their direct innervation of midbrain dopamine neurons. These findings provide new understanding of the intersection of the N/OFQ system among basal ganglia circuits with particular implications for developmental regulation or wiring of striatal-nigral circuits.

Hypogonadism and neurocognitive outcomes among childhood cancer survivors.

OBJECTIVE: Childhood cancer survivors are at risk for hypogonadism. The impact of hypogonadism on neurocognitive impairment and emotional distress in the non-cancer population has been shown; however, the relationship among the childhood cancer survivor population is unknown. We aimed to evaluate the contribution of hypogonadism to neurocognitive impairment and emotional distress among survivors. DESIGN: Cross-sectional study using retrospective cohort. METHODS: In total, 3628 survivors who completed standard neurocognitive tests (six domains: processing speed, memory, executive function, attention, academics, and global cognition) and self-reported emotional distress were included in our study. Participants were stratified by sex and gonadal status. Outcomes were compared between hypogonadal and eugonadal groups by multivariable analysis, adjusting for established predictors, and mediation analyses to determine the direct/indirect effects of hypogonadism on outcomes. RESULTS: The hypogonadal group exhibited a higher prevalence of neurocognitive impairment across domains, but no difference in emotional distress. Hypogonadal females exhibited higher relative risk (1.7, 95% CI, 1.2-2.5) for impaired visual processing speed, compared to eugonadal females after adjusting for cancer-related variables. In mediation models, hypogonadism had a significant direct (P < .01) and indirect (from P < .01) impact on impairment in visual processing speed among females. Males demonstrated direct (P = .03) and indirect (P = .04) impact of hypogonadism on motor processing speed. CONCLUSION: Processing speed may be the most vulnerable neurocognitive domain associated with hypogonadism in survivors, while other domains were mainly impacted by cancer-related variables. Our findings support the need for further evaluation of the impact of sex hormone replacement therapy on neurocognitive function.

Impact of Childhood Cancer on Growth.

Along with improvements in cancer treatment over time, the number of childhood cancer survivors has been growing. Survivors are at risk for serious medical complications, and growth impairment is among the most common. There are multiple factors that may cause impaired growth among survivors. In this article, we review the impact of cancer on growth in children and adolescents. We first provide an overview of growth disturbance among childhood cancer patients and survivors due to nonhormonal causes, including a recent understanding of the effect of targeted cancer therapies (eg, tyrosine kinase inhibitors and immune checkpoint inhibitors) on growth. Then we describe the hormonal causes of growth impairment among survivors, focusing on growth hormone deficiency, including the prevalence, risk factors, and treatment. Lastly, we briefly summarize overgrowth and tall stature in childhood cancer. It is critical to assess the linear growth of children and adolescents, especially in cancer survivors who are at risk for growth disturbance, since growth is an important measure of their health.

Variations in gender identity and sexual orientation of university students.

Background: Previous studies have shown that a small percentage of people in the general population have atypical gender identity and/or sexual orientation. Aim: This study aimed to explore variations in gender identity and sexual orientation in university students and determine genetic factors associated with these variations. Methods: Deviations from complete gender congruence and exclusive heterosexual orientation in 736 Japanese university students were quantitatively assessed with self-assessment questionnaires. Next, we conducted genetic tests for 80 participants who showed relatively low gender identity scores and/or atypical sexual orientation. These genetic tests consisted of repeat number analysis of the androgen receptor gene (AR) and a SKAT-O: an optimal unified sequence kernel association test, which is an exome-based rare variant association study. The results of the genetic tests were compared with the Japanese reference data and the results of our 637 control samples. Outcomes: We calculated the gender identity and sexual orientation scores of all participants and analyzed the molecular data of 80 selected participants. Results: The gender identity scores of 736 participants were broadly distributed: only ~15% of natal males and ~5% of natal females had the maximum score that corresponds to complete gender congruence. The sexual orientation scores also varied: ~80% of natal males and ~60% of natal females showed exclusive heterosexual orientation. We found no association between gender characteristics and AR repeat numbers. The SKAT-O showed that rare damaging variants of TDRP and 3 other genes were more common in the 80 participants than in the control group. Clinical Implications: Our data support the view that gender is a phenotypic continuum rather than a binary trait. Strength and Limitations: This study quantitatively assessed the gender characteristics of a large cohort of university students. Moreover, we conducted systematic screening for genetic factors associated with gender variations. The weaknesses of the study were the limited analytic power of the questionnaires, the relatively small sample for molecular analyses, and incomplete clinical information and relatively advanced ages of the control group. Conclusion: This study revealed significant variations in gender identity and sexual orientation in university students, which may be partly associated with variants in TDRP or other genes.

Scalable, flexible carbon fiber electrode thread arrays for three-dimensional probing of neurochemical activity in deep brain structures of rodents.

We developed a flexible "electrode-thread" array for recording dopamine neurochemicals from a lateral distribution of subcortical targets (up to 16) transverse to the axis of insertion. Ultrathin (∼10 µm diameter) carbon fiber (CF) electrode-threads (CFETs) are clustered into a tight bundle to introduce them into the brain from a single-entry point. The individual CFETs splay laterally in deep brain tissue during insertion due to their innate flexibility. This spatial redistribution allows navigation of the CFETs towards deep brain targets spreading horizontally from the axis of insertion. Commercial "linear" arrays provide single-entry insertion but only allow measurements along the axis of insertion. Horizontally configured arrays inflict separate penetrations for each individual channel. We tested functional performance of our CFET arrays in vivo for recording dopamine and for providing lateral spread to multiple distributed sites in the rat striatum. Spatial spread was further characterized in agar brain phantoms as a function of insertion depth. We also developed protocols to slice the embedded CFETs within fixed brain tissue using standard histology. This method allowed extraction of the precise spatial coordinates of the implanted CFETs and their recording sites as integrated with immunohistochemical staining for surrounding anatomical, cytological, and protein expression labels. Our CFET array has the potential to unlock a wide range of applications, from uncovering the role of neuromodulators in synaptic plasticity, to addressing critical safety barriers in clinical translation towards diagnostic and adaptive treatment in Parkinson's disease and major mood disorders.

Dopamine Release Plateau and Outcome Signals in Dorsal Striatum Contrast with Classic Reinforcement Learning Formulations.

We recorded dopamine release signals in medial and lateral sectors of the striatum as mice learned consecutive visual cue-outcome conditioning tasks including cue association, cue discrimination, reversal, and probabilistic discrimination task versions. Dopamine release responses in medial and lateral sites exhibited learning-related changes within and across phases of acquisition. These were different for the medial and lateral sites. In neither sector could these be accounted for by classic reinforcement learning as applied to dopamine-containing neuron activity. Cue responses ranged from initial sharp peaks to modulated plateau responses. In the medial sector, outcome (reward) responses during cue conditioning were minimal or, initially, negative. By contrast, in lateral sites, strong, transient dopamine release responses occurred at both cue and outcome. Prolonged, plateau release responses to cues emerged in both regions when discriminative behavioral responses became required. In most sites, we found no evidence for a transition from outcome to cue signaling, a hallmark of temporal difference reinforcement learning as applied to midbrain dopamine activity. These findings delineate reshaping of dopamine release activity during learning and suggest that current views of reward prediction error encoding need review to accommodate distinct learning-related spatial and temporal patterns of striatal dopamine release in the dorsal striatum.

Heterogeneous Single-Atom Zinc on Nitrogen-Doped Carbon Catalyzed Electrochemical Allylation of Imines.

Organometallic reagents are effective for carbon-carbon bond formation; however, consumption of stoichiometric amounts of metals is problematic. We developed electrochemical allylation reactions of imines catalyzed by nitrogen-doped carbon-supported single-atom zinc, which were fixed on a cathode to afford a range of homoallylic amines efficiently. The system could suppress generation of metallic waste, and the catalyst electrode showed advantages over bulk zinc in terms of activity and robustness. An electrochemical flow reaction was also successfully performed to produce the homoallylic amine continuously with minimum amounts of waste.

Scalable, flexible carbon fiber electrode thread arrays for three-dimensional spatial profiling of neurochemical activity in deep brain structures of rodents.

We developed a flexible "electrode-thread" array for recording dopamine neurochemical activity from a lateral distribution of subcortical targets (up to 16) transverse to the axis of insertion. Ultrathin (∼ 10 µm diameter) carbon fiber (CF) electrode-threads (CFETs) are clustered into a tight bundle to introduce them into the brain from a single entry point. The individual CFETs splay laterally in deep brain tissue during insertion due to their innate flexibility. This spatial redistribution allows navigation of the CFETs towards deep brain targets spreading horizontally from the axis of insertion. Commercial "linear" arrays provide single entry insertion but only allow measurements along the axis of insertion. Horizontally configured neurochemical recording arrays inflict separate penetrations for each individual channel (i.e., electrode). We tested functional performance of our CFET arrays in vivo for recording dopamine neurochemical dynamics and for providing lateral spread to multiple distributed sites in the striatum of rats. Spatial spread was further characterized using agar brain phantoms to measure electrode deflection as a function of insertion depth. We also developed protocols to slice the embedded CFETs within fixed brain tissue using standard histology techniques. This method allowed extraction of the precise spatial coordinates of the implanted CFETs and their recording sites as integrated with immunohistochemical staining for surrounding anatomical, cytological, and protein expression labels. Neurochemical recording operations tested here can be integrated with already widely established capabilities of CF-based electrodes to record single neuron activity and local field potentials, to enable multi-modal recording functions. Our CFET array has the potential to unlock a wide range of applications, from uncovering the role of neuromodulators in synaptic plasticity, to addressing critical safety barriers in clinical translation towards diagnostic and adaptive treatment in Parkinson's disease and major mood disorders.

DARPP-32 cells and neuropil define striosomal system and isolated matrix cells in human striatum.

The dorsal striatum forms a central node of the basal ganglia interconnecting the neocortex and thalamus with circuits modulating mood and movement. Striatal projection neurons (SPNs) include relatively intermixed populations expressing D1-type or D2-type dopamine receptors (dSPNs and iSPNs) that give rise to the direct (D1) and indirect (D2) output systems of the basal ganglia. Overlaid on this organization is a compartmental organization, in which a labyrinthine system of striosomes made up of sequestered SPNs is embedded within the larger striatal matrix. Striosomal SPNs also include D1-SPNs and D2-SPNs, but they can be distinguished from matrix SPNs by many neurochemical markers. In the rodent striatum the key signaling molecule, DARPP-32, is a exception to these compartmental expression patterns, thought to befit its functions through opposite actions in both D1- and D2-expressing SPNs. We demonstrate here, however, that in the dorsal human striatum, DARPP-32 is concentrated in the neuropil and SPNs of striosomes, especially in the caudate nucleus and dorsomedial putamen, relative to the matrix neuropil in these regions. The generally DARPP-32-poor matrix contains scattered DARPP-32-positive cells. DARPP-32 cell bodies in both compartments proved negative for conventional intraneuronal markers. These findings raise the potential for specialized DARPP-32 expression in the human striosomal system and in a set of DARPP-32-positive neurons in the matrix. If DARPP-32 immunohistochemical positivity predicts differential functional DARPP-32 activity, then the distributions demonstrated here could render striosomes and dispersed matrix cells susceptible to differential signaling through cAMP and other signaling systems in health and disease. DARPP-32 is highly concentrated in cells and neuropil of striosomes in post-mortem human brain tissue, particularly in the dorsal caudate nucleus. Scattered DARPP-32-positive cells are found in the human striatal matrix. Calbindin and DARPP-32 do not colocalize within every spiny projection neuron in the dorsal human caudate nucleus.

Exome-based genome-wide screening of rare variants associated with the risk of polycystic ovary syndrome.

Purpose: Genetic factors associated with the risk of polycystic ovary syndrome (PCOS) remain largely unknown. Here, we conducted an optimal sequence kernel association test (SKAT-O), an exome-based rare variant association study, to clarify whether rare variants in specific genes contribute to the development of PCOS. Methods: SKAT-O was performed using exome data of 44 Japanese patients with PCOS and 301 control women. We analyzed frequencies of rare probably damaging variants in the genome. Results: Rare variants of GSTO2 were more commonly identified in the patient group than in the control group (6/44 vs. 1/301; Bonferroni-corrected p-value, 0.028), while the frequencies of variants in other genes were comparable between the two groups. The identified GSTO2 variants were predicted to affect the function, structure, stability, hydrophobicity, and/or the formation of intrinsically disordered regions of the protein. GSTO2 encodes a glutathione transferase that mediates the oxidative stress response and arsenic metabolism. Previously, common variants in GSTO2 and its paralog GSTO1 were associated with the risk of PCOS. Conclusions: The results indicate that there are no genes whose rare variants account for a large fraction of the etiology of PCOS, although rare damaging variants in GSTO2 may constitute a risk factor in some cases.

Cannabinoid Receptor 1 Is Required for Neurodevelopment of Striosome-Dendron Bouquets.

Cannabinoid receptor 1 (CB1R) has strong effects on neurogenesis and axon pathfinding in the prenatal brain. Endocannabinoids that activate CB1R are abundant in the early postnatal brain and in mother's milk, but few studies have investigated their function in newborns. We examined postnatal CB1R expression in the major striatonigral circuit from striosomes of the striatum to the dopamine-containing neurons of the substantia nigra. CB1R enrichment was first detectable between postnatal day (P)5 and P7, and this timing coincided with the formation of "striosome-dendron bouquets," the elaborate anatomic structures by which striosomal neurons control dopaminergic cell activity through inhibitory synapses. In Cnr1-/- knock-out mice lacking CB1R expression, striosome-dendron bouquets were markedly disorganized by P11 and at adulthood, suggesting a postnatal pathfinding connectivity function for CB1R in connecting striosomal axons and dopaminergic neurons analogous to CB1R's prenatal function in other brain regions. Our finding that CB1R plays a major role in postnatal wiring of the striatonigral dopamine-control system, with lasting consequences at least in mice, points to a crucial need to determine whether lactating mothers' use of CB1R agonists (e.g., in marijuana) or antagonists (e.g., type 2 diabetes therapies) can disrupt brain development in nursing offspring.

Synthesis of meso-porous α-Ga2O3 from liquid Ga metal having significantly high photocatalytic activity for CO2 reduction with water.

We have succeeded in synthesizing meso-porous α-Ga2O3 which shows significantly high photocatalytic activity for CO2 reduction with water. The sample was synthesized by hydroxidation of liquid Ga metal in water to obtain GaOOH and Ga(OH)3, followed by the calcination of the mixed hydroxides at 773 K for 1 hour which converted them to meso-porous α-Ga2O3. The nano-pores remained as the trace of the evaporation of water produced by the oxidation of the hydroxides during the calcination. The photocatalytic activity of the synthesized meso-porous α-Ga2O3 for CO2 reduction with water was as high as or higher than previous studies using various types of Ga2O3 with and without cocatalysts.

Massive digital gene expression analysis reveals different predictive profiles for immune checkpoint inhibitor therapy between adenocarcinoma and squamous cell carcinoma of advanced lung cancer.

BACKGROUND: Immune checkpoint inhibitors prolong the survival of non-small cell lung cancer (NSCLC) patients. Although it has been acknowledged that there is some correlation between the efficacy of anti-programmed cell death-1 (PD-1) antibody therapy and immunohistochemical analysis, this technique is not yet considered foolproof for predicting a favorable outcome of PD-1 antibody therapy. We aimed to predict the efficacy of nivolumab based on a comprehensive analysis of RNA expression at the gene level in advanced NSCLC. METHODS: This was a retrospective study on patients with NSCLC who were administered nivolumab at the Kansai Medical University Hospital. To identify genes associated with response to anti-PD-1 antibodies, we grouped patients into responders (complete and partial response) and non-responders (stable and progressive disease) to nivolumab therapy. Significant genes were then identified for these groups using Welch's t-test. RESULTS: Among 42 analyzed cases (20 adenocarcinomas and 22 squamous cell carcinomas), enhanced expression of MAGE-A4, BBC3, and OTOA genes was observed in responders with adenocarcinoma, and enhanced expression of DAB2, HLA-DPB,1 and CDH2 genes was observed in responders with squamous cell carcinoma. CONCLUSIONS: This study predicted the efficacy of nivolumab based on a comprehensive analysis of mRNA expression at the gene level in advanced NSCLC. We also revealed different gene expression patterns as predictors of the effectiveness of anti PD-1 antibody therapy in adenocarcinoma and squamous cell carcinoma.

Influence of Ag Clusters on the Electronic Structures of ß-Ga2O3 Photocatalyst Surfaces.

In order to understand the photocatalytic carbon dioxide reduction over Ag-loaded ß-Ga2O3 photocatalysts, first principles calculations based on density functional theory were performed on the surface model of a Ag cluster-adsorbed ß-Ga2O3 system. The stable adsorption structures of Ag n (n = 1 to 4) clusters on the ß-Ga2O3 (100) surface were determined. In the electronic structure analysis, the valence states of all Ag clusters mixed with the top of the O 2p valence band of Ga2O3, leading the Fermi level of Ag n /ß-Ga2O3 to shift to the bottom of the conduction band. It was also revealed that the unoccupied states of Ag n clusters overlapped with the Ga unoccupied states, and occupied electronic states of Ag clusters were formed in the band gap. These calculation results corresponded to the experimental ones obtained in our previous study, i.e., small Ag clusters had strong interaction with the Ga2O3 surface, enhancing the electron transfer between the Ag clusters and the Ga2O3 surface. That is, excited electrons toward Ag n clusters or the perimeter of Ag-Ga2O3 should be the important key to promote photocatalytic CO2 reduction.

Synthesis of α-Ga2O3 by Water Oxidation of Metallic Gallium as a Photocatalyst for CO2 Reduction with Water.

We have succeeded to synthesize gallium oxide consisting of α-phase (α-Ga2O3) with the calcination of GaOOH obtained by a direct reaction of liquid Ga metal with water for the first time and found that α-Ga2O3 exhibits photocatalytic activity for CO2 reduction with water and water splitting as well. The calcination above 623 K converted GaOOH to α-Ga2O3, and the samples calcined at 723-823 K were well crystallized to α-Ga2O3 and promoted photocatalytic CO2 reduction with water, producing CO, H2, and O2. This is observed for the first time that α-Ga2O3 without a cocatalyst has shown very high photocatalytic activity for the conversion of CO2 to CO.

Quantification of androgens and their precursors in full-term human placenta.

INTRODUCTION: The two major androgens in humans are testosterone (T) and dihydrotestosterone (DHT). DHT is produced via the classical, backdoor, and alternative steroidogenic pathways. In addition, recent studies have identified C11-oxy C19 steroids as novel human androgens. Although the placenta is known to be involved in steroid metabolism, androgen levels in full-term placentas have poorly been investigated. SUBJECTS AND METHODS: Ten placentas of healthy full-term neonates (five males and five females) were examined. We quantified progesterone, androstenedione (A4), T, allopregnanolone, androsterone, and estradiol, as well as four C11-oxy androgens (11ß-hydroxyandrostenedione, 11ß-hydroxytestosterone, 11-ketoandrostenedione (11KA4), and 11-ketotestosterone (11KT)), using liquid chromatography-tandem mass spectrometry. RESULTS: In all samples, levels of the ten steroids were above the detection limit. Progesterone was by far most abundant, while levels of T and androsterone were relatively low. Levels of 11KT and 11KA4 were higher than those of T and A4, respectively. There were no differences in steroid levels between male and female samples. DISCUSSION: This study demonstrates that full-term placentas contain several steroids in the classical, backdoor, and alternative pathways. Placentas are likely to function as the supplier of progesterone to other steroidogenic tissues. More importantly, we found that placentas comprise relatively large amounts of 11KA4 and 11KT, which may be produced through steroid transfer from the adrenal gland or from the maternal circulation. These results indicate that the placenta participates in a feto-maternal multi-organ network for androgen biosynthesis.

Functional recoveries of patients with branch atheromatous disease after rehabilitation: Comparison with other types of cerebral infarction and importance of stratification by clinical categories.

BACKGROUND: Functional recoveries after rehabilitation of patients with branch atheromatous disease (BAD) have not been well investigated, however, clinical category of cerebral infarction including BAD itself could be a potential predictive factor for functional outcome. OBJECTIVE: To describe characteristics of functional recoveries of patients with BAD through comparison with other types of cerebral infarction. METHODS: We retrospectively compared outcomes of patients with BAD (N = 222), cardioembolic cerebral infarction (CE: N = 177) and atherothrombotic cerebral infarction (AT: N = 219) by using functional independence measure (FIM) and FIM effectiveness (the proportion of potential for improvement achieved). RESULTS: Univariate analysis showed that FIM on discharge was comparable among three types of cerebral infarction, but that FIM effectiveness in patients with BAD was significantly higher than those with CE or AT. Stratified analysis revealed higher FIM effectiveness in patients with BAD compared to patients with CE or AT, if they were male, younger (≤72 years) or had supratentorial brain lesions. Multiple regression analysis demonstrated that location of the brain lesion (supratentorial vs infratentorial) and gender (male vs female) were significantly associated with FIM on discharge, and that cognitive function on admission as well as gender were significantly associated with FIM effectiveness in patients with BAD, but not in patients with CE or AT. CONCLUSIONS: Outcomes after rehabilitation of patients with BAD may be characterized by better functional improvement, especially if patients are male, relatively younger or with supratentorial lesions. The impact and the type of factors related to functional recoveries of patients with BAD may be different from other types of stroke. The present study suggested that clinical category of stroke should be taken into consideration in prediction of outcomes and planning of rehabilitation management.

The role of the shell in core-shell-structured La-doped NaTaO3 photocatalysts.

NaTaO3, a semiconductor with a perovskite structure, has long been known as a highly active photocatalyst for overall water splitting when appropriately doped with La cations. A profound understanding of the surface feature and why and how it may control the water splitting activity is critical because redox reactions take place at the surface. One surface feature characteristic of La-doped NaTaO3 is a La-rich layer (shell) capping La-poor bulk (core). In this study, we investigate the role of the shell in core-shell-structured La-doped NaTaO3 through systematic chemical etching with an aqueous HF solution. We find that the La-rich shell plays a role in electron-hole recombination, electron mobility and water splitting activity. The shallow electron traps populating the La-rich shell trap the photoexcited electrons, decreasing their mobility. The shallowly trapped electrons remain reactive and are readily available on the surface to be extracted by the cocatalysts for the reduction reaction evolving H2. The presently employed chemical etching method also confirms the presence of a La concentration gradient in the core that regulates the steady-state electron population and water splitting activity. Here, we successfully reveal the nanoarchitecture-photoactivity relationship of core-shell-structured La-doped NaTaO3 that thereby allows tuning of the surface features and spatial distribution of dopants to increase the concentration of photoexcited electrons and therefore the water splitting activity. By recognizing the key factors that control the photocatalytic properties of a highly active catalyst, we can then devise proper strategies to design new photocatalyst materials with breakthrough performances.

Similar responsiveness between C57BL/6N and C57BL/6J mouse substrains to superovulation.

Superovulation is a method for the drug-induced release of multiple eggs and useful for in vitro fertilization. Thus, its high efficiency largely reduces the number of mice used per experiment. We compared the responsivity to superovulation between C57BL/6N (B6N) and C57BL/6J (B6J) substrains. The average number of ovulated eggs was strikingly higher in both substrains treated with anti-inhibin serum (AIS) plus equine chorionic gonadotropin (eCG) than those treated with eCG alone. Our data indicate that hypothalamus-pituitary-ovarian axis similarly responds to eCG treatment in B6N and B6J mice, and that this responsiveness is enhanced by the presence of AIS.