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In spite of emphasis on patient-centered care and promotion of their quality, shortcomings have been seen in psychiatric care due to lack of compassion. To improve the quality of psychiatric caring in nursing, it is important to develop and implement in-service education based on Locsin’s Technological Competency as Caring in Nursing (TCCN) theory. Objectives to determine psychiatric nurse managers' perception and practice status as a preliminary survey to serve as a resource for in-service psychiatric nursing education. This survey was conducted in August 2022 using the Technological Competency as Caring in Nursing Instrument-Revised for Practice (TCCNI-Repract) scale at "A" psychiatric hospital. Descriptive statistics and Wilcoxon's signed-rank tests were used. Eleven head nurses and assistant head nurses participated in this study. Mean values for the perception dimension of each item of the TCCNI-RePract were high, whereas mean values for practice dimension were low. The results indicated that perception dimension was significantly higher than practice dimension in 21 of 26 items of the TCCNI-RePract. Nurse managers demonstrated a high level of perception of the TCCN theory; however, many practical items scored low. Nurse managers suggested developing a current educational program to inform practice based on the TCCN theory.

Although main pancreatic duct dilatation and pancreatic cysts are risk factors for developing pancreatic cancer, limited data exist regarding these findings in relatives and spouses of pancreatic cancer patients. The frequency of these findings was examined using long-term follow-up data and transabdominal ultrasonography focusing on the pancreas. We prospectively enrolled 184 relatives and spouses of pancreatic cancer patients and performed special pancreatic ultrasonography to detect main pancreatic duct dilatation and pancreatic cysts. First-degree relatives (148 participants) of patients with pancreatic cancer were significantly younger than the spouses (36 participants; 41 vs. 65 years old). The frequency of ultrasonographic findings was significantly different between the relative (8.8%) and spouse (33.3%) groups. Main pancreatic duct dilatation and pancreatic cysts were observed in seven (4.7%) and seven (4.7%) participants in the relative group, and in nine (25.0%) and five (13.9%) participants in the spouse group, respectively. On multivariate analysis, age was an independent risk factor for the ultrasonographic findings. The frequency of ultrasonographic findings was significantly higher in spouses than in first-degree relatives of patients with pancreatic cancer and was strongly influenced by the age gap between the groups. Main pancreatic duct dilatation was frequently observed, especially in the spouse group.

Summary: A truncating mutation in the mouse Srrm4 gene, which encodes a neuronal splicing factor, causes alternative splicing defects selectively in the ear. The mechanism by which splicing is preserved in the brain of these mice is not known. Here, we show that SRRM3 limits the Srrm4 mutation-associated defects to the ear and that, in cortical neurons, overlapping SRRM3-SRRM4 activity regulates the development of interneuronal inhibition. In vitro, SRRM3 and SRRM4 regulate the same splicing events, but a mutation in mouse Srrm3 causes tremors and mild defects in neuronal alternative splicing, demonstrating unique SRRM3 roles in vivo. Mice harboring mutations in both Srrm3 and Srrm4 die neonatally and exhibit severe splicing defects. In these mice, splicing alterations prevent inactivation of the gene repressor REST, which maintains immature excitatory GABAergic neurotransmission by repressing K-Cl cotransporter 2. Thus, our data reveal that SRRM3 and SRRM4 act redundantly to regulate GABAergic neurotransmission by inactivating REST. : Nakano et al. report that the paralogous proteins SRRM3 and SRRM4 regulate the alternative splicing of overlapping groups of exons in the CNS and that the SRRM3-SRRM4-regulated splicing alterations change GABAergic neurotransmission from excitatory to inhibitory during development by inactivating the gene repressor REST and derepressing its target gene Kcc2. Keywords: alternative splicing, gene expression regulation, neuronal development, GABAergic neurotransmission, SRRM3, SRRM4, REST, KCC2, GABA-A receptor, calcium imaging

Solvent chirality transfer of (S)-/(R)-limonenes allows the instant generation of optically active PF8P2 aggregates with distinct circular dichroism (CD)/circularly polarized luminescence (CPL) amplitudes with a high quantum yield of 16–20%. The present paper also reports subtle mirror-symmetry-breaking effects in CD-/CPL-amplitude and sign, CD/UV-vis spectral wavelengths, and photodynamics of the aggregates, though the reasons for the anomaly are unsolved. However, these photophysical properties depend on (i) the chemical natures of chiral and achiral molecules when used in solvent quantity, (ii) clockwise and counterclockwise stirring operations, and (iii) the order of addition of limonene and methanol to the chloroform solution.

The phenotype of the spontaneous mutant mouse hop-sterile (hop) is characterized by a hopping gait, polydactyly, hydrocephalus, and male sterility. Previous analyses of the hop mouse revealed a deficiency of inner dynein arms in motile cilia and a lack of sperm flagella, potentially accounting for the hydrocephalus and male sterility. The etiology of the other phenotypes and the location of the hop mutation remained unexplored. Here we show that the hop mutation is located in the Ttc26 gene and impairs Hedgehog (Hh) signaling. Expression analysis showed that this mutation led to dramatically reduced levels of the Ttc26 protein, and protein-protein interaction assays demonstrated that wild-type Ttc26 binds directly to the Ift46 subunit of Intraflagellar Transport (IFT) complex B. Although IFT is required for ciliogenesis, the Ttc26 defect did not result in a decrease in the number or length of primary cilia. Nevertheless, Hh signaling was reduced in the hop mouse, as revealed by impaired activation of Gli transcription factors in embryonic fibroblasts and abnormal patterning of the neural tube. Unlike the previously characterized mutations that affect IFT complex B, hop did not interfere with Hh-induced accumulation of Gli at the tip of the primary cilium, but rather with the subsequent dissociation of Gli from its negative regulator, Sufu. Our analysis of the hop mouse line provides novel insights into Hh signaling, demonstrating that Ttc26 is necessary for efficient coupling between the accumulation of Gli at the ciliary tip and its dissociation from Sufu.

Sensory hair cells are essential for hearing and balance. Their development from epithelial precursors has been extensively characterized with respect to transcriptional regulation, but not in terms of posttranscriptional influences. Here we report on the identification and functional characterization of an alternative-splicing regulator whose inactivation is responsible for defective hair-cell development, deafness, and impaired balance in the spontaneous mutant Bronx waltzer (bv) mouse. We used positional cloning and transgenic rescue to locate the bv mutation to the splicing factor-encoding gene Ser/Arg repetitive matrix 4 (Srrm4). Transcriptome-wide analysis of pre-mRNA splicing in the sensory patches of embryonic inner ears revealed that specific alternative exons were skipped at abnormally high rates in the bv mice. Minigene experiments in a heterologous expression system confirmed that these skipped exons require Srrm4 for inclusion into the mature mRNA. Sequence analysis and mutagenesis experiments showed that the affected transcripts share a novel motif that is necessary for the Srrm4-dependent alternative splicing. Functional annotations and protein-protein interaction data indicated that the encoded proteins cluster in the secretion and neurotransmission pathways. In addition, the splicing of a few transcriptional regulators was found to be Srrm4 dependent, and several of the genes known to be targeted by these regulators were expressed at reduced levels in the bv mice. Although Srrm4 expression was detected in neural tissues as well as hair cells, analyses of the bv mouse cerebellum and neocortex failed to detect splicing defects. Our data suggest that Srrm4 function is critical in the hearing and balance organs, but not in all neural tissues. Srrm4 is the first alternative-splicing regulator to be associated with hearing, and the analysis of bv mice provides exon-level insights into hair-cell development.

Hereditary hearing loss is one of the most common birth defects, yet the majority of genes required for audition is thought to remain unidentified. Ethylnitrosourea (ENU)-mutagenesis has been a valuable approach for generating new animal models of deafness and discovering previously unrecognized gene functions. Here we report on the characterization of a new ENU-induced mouse mutant (nmf329) that exhibits recessively inherited deafness. We found a widespread loss of sensory hair cells in the hearing organs of nmf329 mice after the second week of life. Positional cloning revealed that the nmf329 strain carries a missense mutation in the claudin-9 gene, which encodes a tight junction protein with unknown biological function. In an epithelial cell line, heterologous expression of wild-type claudin-9 reduced the paracellular permeability to Na+ and K+, and the nmf329 mutation eliminated this ion barrier function without affecting the plasma membrane localization of claudin-9. In the nmf329 mouse line, the perilymphatic K+ concentration was found to be elevated, suggesting that the cochlear tight junctions were dysfunctional. Furthermore, the hair-cell loss in the claudin-9-defective cochlea was rescued in vitro when the explanted hearing organs were cultured in a low-K+ milieu and in vivo when the endocochlear K+-driving force was diminished by deletion of the pou3f4 gene. Overall, our data indicate that claudin-9 is required for the preservation of sensory cells in the hearing organ because claudin-9-defective tight junctions fail to shield the basolateral side of hair cells from the K+-rich endolymph. In the tight-junction complexes of hair cells, claudin-9 is localized specifically to a subdomain that is underneath more apical tight-junction strands formed by other claudins. Thus, the analysis of claudin-9 mutant mice suggests that even the deeper (subapical) tight-junction strands have biologically important ion barrier function.

Mutations in the gene encoding Cu-Zn superoxide dismutase (SOD1) are one of the causes of familial amyotrophic lateral sclerosis (FALS). Fibrillar inclusions containing SOD1 and SOD1 inclusions that bind the amyloid-specific dye thioflavin S have been found in neurons of transgenic mice expressing mutant SOD1. Therefore, the formation of amyloid fibrils from human SOD1 was investigated. When agitated at acidic pH in the presence of low concentrations of guanidine or acetonitrile, metalated SOD1 formed fibrillar material which bound both thioflavin T and Congo red and had circular dichroism and infrared spectra characteristic of amyloid. While metalated SOD1 did not form amyloid-like aggregates at neutral pH, either removing metals from SOD1 with its intramolecular disulfide bond intact or reducing the intramolecular disulfide bond of metalated SOD1 was sufficient to promote formation of these aggregates. SOD1 formed amyloid-like aggregates both with and without intermolecular disulfide bonds, depending on the incubation conditions, and a mutant SOD1 lacking free sulfhydryl groups (AS-SOD1) formed amyloid-like aggregates at neutral pH under reducing conditions. ALS mutations enhanced the ability of disulfide-reduced SOD1 to form amyloid-like aggregates, and apo-AS-SOD1 formed amyloid-like aggregates at pH 7 only when an ALS mutation was also present. These results indicate that some mutations related to ALS promote formation of amyloid-like aggregates by facilitating the loss of metals and/or by making the intramolecular disulfide bond more susceptible to reduction, thus allowing the conversion of SOD1 to a form that aggregates to form resembling amyloid. Furthermore, the occurrence of amyloid-like aggregates per se does not depend on forming intermolecular disulfide bonds, and multiple forms of such aggregates can be produced from SOD1.

BackgroundIn single-cell human genome analysis using whole-genome amplified product, a strong amplification bias involving allele dropout and preferential amplification hampers the quality of results. Using an oligonucleotide single nucleotide polymorphism (SNP) array, we systematically examined the nature of this amplification bias, including frequency, degree, and preference for genomic location, and we assessed the effects of this amplification bias on subsequent genotype and chromosomal copy number analyses.Methodology/principal findingsWe found a large variability in amplification bias among the amplified products obtained by multiple displacement amplification (MDA), and this bias had a severe effect on the genotype and chromosomal copy number analyses. We established optimal experimental conditions for pre-screening for high-quality amplified products, processing array data, and analyzing chromosomal structural alterations. Using this optimized protocol, we successfully detected previously unidentified chromosomal structural alterations in single cells from a lymphoblastoid cell line. These alterations were subsequently confirmed by karyotype analysis. In addition, we successfully obtained reproducible chromosomal copy number profiles of single cells from the cell line with a complex karyotype, indicating the applicability and potential of our optimized workflow.Conclusions/significanceOur results suggest that the quality of amplification products should be critically assessed before using them for genomic analyses. The method of MDA-based whole-genome amplification followed by SNP array analysis described here will be useful for exploring chromosomal alterations in single cells.

For more than three decades it has been known, that striatal neurons become hyperactive after the loss of dopamine input, but the involvement of dopamine (DA) D1-or D2-receptor-expressing neurons has only been demonstrated indirectly. By recording neuronal activity using fluorescent calcium indicators in D1 or D2 eGFP-expressing mice, we showed that following dopamine depletion, both types of striatal output neurons are involved in the large increase in neuronal activity generating a characteristic cell assembly of particular neurons that dominate the pattern. When we expressed channelrhodopsin in all the output neurons, light activation in freely moving animals, caused turning like that following dopamine loss. However, if the light stimulation was patterned in pulses the animals circled in the other direction. To explore the neuronal participation during this stimulation we infected normal mice with channelrhodopsin and calcium indicator in striatal output neurons. In slices made from these animals, continuous light stimulation for 15 s induced many cells to be active together and a particular dominant group of neurons, whereas light in patterned pulses activated fewer cells in more variable groups. These results suggest that the simultaneous activity of a large dominant group of striatal output neurons is intimately associated with parkinsonian symptoms. [ABSTRACT FROM AUTHOR]

The current study investigates to what extent masked morphological priming is modulated by language-particular properties, specifically by its writing system. We present results from two masked priming experiments investigating the processing of complex Japanese words written in less common (moraic) scripts. In Experiment 1, participants performed lexical decisions on target verbs; these were preceded by primes which were either (i) a past-tense form of the same verb, (ii) a stem-related form with the epenthetic vowel -i, (iii) a semantically-related form, and (iv) a phonologically-related form. Significant priming effects were obtained for prime types (i), (ii), and (iii), but not for (iv). This pattern of results differs from previous findings on languages with alphabetic scripts, which found reliable masked priming effects for morphologically related prime/target pairs of type (i), but not for non-affixal and semantically-related primes of types (ii), and (iii). In Experiment 2, we measured priming effects for prime/target pairs which are neither morphologically, semantically, phonologically nor - as presented in their moraic scripts--orthographically related, but which--in their commonly written form--share the same kanji, which are logograms adopted from Chinese. The results showed a significant priming effect, with faster lexical-decision times for kanji-related prime/target pairs relative to unrelated ones. We conclude that affix-stripping is insufficient to account for masked morphological priming effects across languages, but that language-particular properties (in the case of Japanese, the writing system) affect the processing of (morphologically) complex words. [ABSTRACT FROM AUTHOR]

Objective: To quantify negative aesthetic ratings in primary unrepaired cleft lip infants by further refining our previously reported paired comparison method. Design: The Thurstone paired comparison method was used to quantify negative aesthetic ratings of plaster facial models selected and ordered according to a table of paired random numbers. Patients, Participants: A total of 30 facial models of unrepaired incomplete unilateral cleft lip infants were used in this study. Raters comprised 20 oral surgeons and anesthesiologists. Results: Quantification of aesthetic ratings for the 30 face models of unrepaired incomplete unilateral cleft lip infants was obtained. The ratings ranged from 0 to 5.08. Conclusion: Quantification of the aesthetic ratings for the 30 face models will be used as objective variables in a multivariate analysis in the third stage of this ongoing study. [ABSTRACT FROM AUTHOR]

A detailed analysis of the conformational states of self-assembled, stereoselectively deuterated benzene-1,3,5-tricarboxamides ((S,S,S)-D-BTAs) reveals four different conformers for the supramolecular polymers. The relative amount of the conformers depends on the solvent structure and the temperature. With the help of a model, the thermodynamic parameters that characterize the different conformational states were quantified as well as the amount of the species that occur at different stages of the polymerization process. The results show that small changes in the stability between different types of conformers formed by (S,S,S)-D-BTAs—in the order of a few J mol–1—arise from the combination of interactions between the solvent/supramolecular aggregate, temperature, and solvent structure. While the introduction of a deuterium label allows to sensitively probe the solvophobic effects in the supramolecular aggregation, a rationalization of the observed effects on a molecular level is not yet straightforward but is proposed to result from subtle effects in the vibrational enthalpy and entropy terms of the isotope effect. [ABSTRACT FROM AUTHOR]

Objective: Postoperative evaluation of bone formation in the alveolar cleft by computed tomography imaging has been reported. We quantitatively evaluated bone grafts in the alveolar cleft preoperatively and postoperatively using three-dimensional data and superimposition of images. Subjects: A total of 12 patients with complete unilateral cleft lip and palate (six left-sided and six right-sided) were studied. Methods: Helical computed tomography scans were taken immediately before surgery and at 6 months after surgery and the DICOM files obtained were processed using Mimics and 3-matic software for three-dimensional data analysis. The preoperative and postoperative computed tomography data were superimposed, and the position and length of the unerupted canines and width of the alveolar cleft measured. Results: Strong and significant correlations were observed between bone formation in the alveolar cleft bone graft region and preoperative canine position (r= -.766, p < .01) and canine length (r = .681, p < .05). Stepwise multiple regression analysis demonstrated that only the preoperative canine position was independently and significantly correlated with bone formation in the alveolar cleft. Conclusion: These results indicate that the optimal timing for surgery is when the canine cusp is close to the alveolar plane. [ABSTRACT FROM AUTHOR]

Solvent chirality transfer of (S)-/(R)-limonenes allows the instant generation of optically active PF8P2 aggregates with distinct circular dichroism (CD)/circularly polarized luminescence (CPL) amplitudes with a high quantum yield of 16-20%. The present paper also reports subtle mirror-symmetry-breaking effects in CD-/CPL-amplitude and sign, CD/UV-vis spectral wavelengths, and photodynamics of the aggregates, though the reasons for the anomaly are unsolved. However, these photophysical properties depend on (i) the chemical natures of chiral and achiral molecules when used in solvent quantity, (ii) clockwise and counterclockwise stirring operations, and (iii) the order of addition of limonene and methanol to the chloroform solution. [ABSTRACT FROM AUTHOR]

The solid-state chiral optical properties of a 1-pyrenesulfonic acid/amine supramolecular organic fluorophore could be controlled by changing the type of the aromatic ring and not the chirality of the chiral amine component molecule in the solid state. [ABSTRACT FROM AUTHOR]

Otoconia are small biominerals in the inner ear that are indispensable for the normal perception of gravity and motion. Normal otoconia biogenesis requires Nox3, a Nox (NADPH oxidase) highly expressed in the vestibular system. In HEK-293 cells (human embryonic kidney cells) transfected with the Nox regulatory subunits NoxO1 (Nox organizer 1) and NoxA1 (Nox activator 1), functional murine Nox3 was expressed in the plasma membrane and exhibited a haem spectrum identical with that of Nox2, the electron transferase of the phagocyte Nox. In vitro Nox3 cDNA expressed an ∼50 kDa primary translation product that underwent N-linked glycosylation in the presence of canine microsomes. RNAi (RNA interference)-mediated reduction of endogenous p22phox, a subunit essential for stabilization of Nox2 in phagocytes, decreased Nox3 activity in reconstituted HEK-293 cells. p22phox co-precipitated not only with Nox3 and NoxO1 from transfectants expressing all three proteins, but also with NoxO1 in the absence of Nox3, indicating that p22phox physically associated with both Nox3 and with NoxO1. The plasma membrane localization of Nox3 but not of NoxO1 required p22phox. Moreover, the glycosylation and maturation of Nox3 required p22phox expression, suggesting that p22phox was required for the proper biosynthesis and function of Nox3. Taken together, these studies demonstrate critical roles for p22phox at several distinct points in the maturation and assembly of a functionally competent Nox3 in the plasma membrane. [ABSTRACT FROM AUTHOR]

By using racemic (rac)-2-amino-1,2-diphenylethanol and achiral fluorescent 1-fluorenecarboxylic acid, a two-component columnar host system with multiple molecular response (guest-dependent spontaneous resolution and fluorescence) properties in the solid state was created. [ABSTRACT FROM AUTHOR]

The sign of circularly polarized luminescence (CPL) of a chiral 21-helical columnar organic fluorophore was successfully controlled in the solid-state by changing an achiral fluorescence component molecule, and not by using a chiral component molecule with opposite chirality. [ABSTRACT FROM AUTHOR]

We have developed a novel approach to the preparation of a circularly polarized luminescence material from a natural polysaccharide host and an achrial polythiophene guest. [ABSTRACT FROM AUTHOR]