Evolutionary Conservation in Protein-Protein Interactions and Structures of the Elongator Sub-Complex ELP456 from Arabidopsis and Yeast.

The Elongator complex plays a pivotal role in the wobble uridine modification of the tRNA anticodon. Comprising two sets of six distinct subunits, namely, Elongator proteins (ELP1-ELP6) and associated proteins, the holo-Elongator complex demonstrates remarkable functional and structural conservation across eukaryotes. However, the precise details of the evolutionary conservation of the holo-Elongator complex and its individual sub-complexes (i.e., ELP123; ELP456) in plants remain limited. In this study, we conducted an in vivo analysis of protein-protein interactions among Arabidopsis ELP4, ELP5, and ELP6 proteins. Additionally, we predicted their structural configurations and performed a comparative analysis with the structure of the yeast Elp456 sub-complex. Protein-protein interaction analysis revealed that AtELP4 interacts with AtELP6 but not directly with AtELP5. Furthermore, we found that the Arabidopsis Elongator-associated protein, Deformed Roots and Leaves 1 (DRL1), did not directly bind to AtELP proteins. The structural comparison of the ELP456 sub-complex between Arabidopsis and yeast demonstrated high similarity, encompassing the RecA-ATPase fold and the positions of hydrogen bonds, despite their relatively low sequence homology. Our findings suggest that Arabidopsis ELP4, ELP5, and ELP6 proteins form a heterotrimer, with ELP6 serving as a bridge, indicating high structural conservation between the ELP456 sub-complexes from Arabidopsis and yeast.

Association of sleep quality and mitochondrial DNA copy number in healthy middle-aged adults.

OBJECTIVES: Mitochondria contribute to various compromised health, yet the association between sleep and mitochondria remains unclear. This study investigated the association between sleep quality and mitochondrial function in healthy middle-aged adults in the Republic of Korea. METHOD: This cross-sectional study recruited 238 middle-aged adults using convenience sampling. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Mitochondrial function, represented by mitochondrial DNA copy number (mtDNAcn), was measured using real-time quantitative polymerase chain reaction on peripheral blood leukocytes. Multivariate linear regression analyses were performed to determine the association between sleep quality and mtDNAcn. RESULTS: Sleep quality was negatively associated with mtDNAcn (r = -.15, p = .025); the poor sleep quality group had a notably lower mtDNAcn compared to the good sleep quality group (t = 2.40, p = .017). Among the PSQI components, sleep latency was significantly associated with reduced mtDNAcn (r = -.18, p = .005). Univariate regression analysis revealed that mtDNAcn was significantly associated with education level (ß = 0.15, p = .017), shift work (ß = -0.17, p = .010), global PSQI score (ß = -0.15, p = .025), and sleep latency (ß = -0.18, p = .005). After adjusting for educational level and shift work in the final model, longer sleep latency was independently associated with reduced mtDNAcn (ß = -.16, p = .011). CONCLUSIONS: Poor sleep quality is associated with reduced mtDNAcn, suggesting a potential biological mechanism whereby poor sleep quality, specifically long sleep latency, accelerates cellular aging and impairs health through mitochondrial dysfunction. These findings enhance our understanding of the health effects of sleep quality and highlight the importance of screening and intervention strategies for mitochondrial dysfunction.

Beyond NPK: Mineral Nutrient-Mediated Modulation in Orchestrating Flowering Time.

Flowering time in plants is a complex process regulated by environmental conditions such as photoperiod and temperature, as well as nutrient conditions. While the impact of major nutrients like nitrogen, phosphorus, and potassium on flowering time has been well recognized, the significance of micronutrient imbalances and their deficiencies should not be neglected because they affect the floral transition from the vegetative stage to the reproductive stage. The secondary major nutrients such as calcium, magnesium, and sulfur participate in various aspects of flowering. Micronutrients such as boron, zinc, iron, and copper play crucial roles in enzymatic reactions and hormone biosynthesis, affecting flower development and reproduction as well. The current review comprehensively explores the interplay between microelements and flowering time, and summarizes the underlying mechanism in plants. Consequently, a better understanding of the interplay between microelements and flowering time will provide clues to reveal the roles of microelements in regulating flowering time and to improve crop reproduction in plant industries.

AtELP4 a subunit of the Elongator complex in Arabidopsis, mediates cell proliferation and dorsoventral polarity during leaf morphogenesis.

The Elongator complex in eukaryotes has conserved tRNA modification functions and contributes to various physiological processes such as transcriptional control, DNA replication and repair, and chromatin accessibility. ARABIDOPSIS ELONGATOR PROTEIN 4 (AtELP4) is one of the six subunits (AtELP1-AtELP6) in Arabidopsis Elongator. In addition, there is an Elongator-associated protein, DEFORMED ROOTS AND LEAVES 1 (DRL1), whose homolog in yeast (Kti12) binds tRNAs. In this study, we explored the functions of AtELP4 in plant-specific aspects such as leaf morphogenesis and evolutionarily conserved ones between yeast and Arabidopsis. ELP4 comparison between yeast and Arabidopsis revealed that plant ELP4 possesses not only a highly conserved P-loop ATPase domain but also unknown plant-specific motifs. ELP4 function is partially conserved between Arabidopsis and yeast in the growth sensitivity toward caffeine and elevated cultivation temperature. Either single Atelp4 or drl1-102 mutants and double Atelp4 drl1-102 mutants exhibited a reduction in cell proliferation and changed the adaxial-abaxial polarity of leaves. In addition, the single Atelp4 and double Atelp4 drl1-102 mutants showed remarkable downward curling at the whole part of leaf blades in contrast to wild-type leaf blades. Furthermore, our genetic study revealed that AtELP4 might epistatically act on DRL1 in the regulation of cell proliferation and dorsoventral polarity in leaves. Taken together, we suggest that AtELP4 as part of the plant Elongator complex may act upstream of a regulatory pathway for adaxial-abaxial polarity and cell proliferation during leaf development.

Effects of biofeedback-based sleep improvement program on urinary symptoms and sleep patterns of elderly Korean women with overactive bladder syndrome.

BACKGROUND: The prevalence of overactive bladder syndrome (OAB) increases with age. Sleep disturbances in elderly individuals with OAB is a common problem. The purpose of this study was to examine the effects of a biofeedback-based sleep improvement (BBSI) program on urinary symptoms and sleep patterns in elderly Korean women with OAB. METHODS: A non-equivalent control group pre-/post-test design was used. Elderly women with OAB were assigned to an intervention group (n = 20) or a control group (n = 18). The BBSI program was implemented in the intervention group for 12 weeks, while two educational sessions of general sleep hygiene and lifestyle modification were provided to the control group. Using SPSS 23.0, the data were analyzed by descriptive analysis using the chi-square test, Fisher's exact test, Mann-Whitney test, and Wilcoxon test. RESULTS: After the 12-week BBSI program, significant improvements were found in the intervention group's the square root of the mean squared differences of successive R-R intervals (p = 0.025), low frequency/high frequency ratio (p = 0.006), and epinephrine (p = 0.039). We also observed a significant difference in urinary symptoms, sleep efficiency, wake after sleep onset, number of awakenings, and number of awakenings within 3 h after sleep onset (p < 0.001, p = 0.004, p = 0.001, p = 0.001, and p = 0.048, respectively). However, no significant changes were found in these variables in the control group. CONCLUSIONS: The BBSI program effectively improved urinary symptoms and sleep patterns of elderly Korean women with OAB. Further longitudinal research is required to investigate the sustainability and effects of the BBSI program. TRIAL REGISTRATION: KCT0003882. Date of registration: 02/05/2019. Retrospectively registered.

Increased Production of α-Linolenic Acid in Soybean Seeds by Overexpression of Lesquerella FAD3-1.

Soybean is a major crop that is used as a source of vegetable oil for human use. To develop transgenic soybean with high α-linolenic acid (ALA; 18:3) content, the FAD3-1 gene isolated from lesquerella (Physaria fendleri) was used to construct vectors with two different seed-specific promoters, soybean ß-conglycinin (Pß-con) and kidney bean phaseolin (Pphas), and one constitutive cauliflower mosaic virus 35S promoter (P35S). The corresponding vectors were used for Agrobacterium-mediated transformation of imbibed mature half seeds. The transformation efficiency was approximately 2%, 1%, and 3% and 21, 7, and 17 transgenic plants were produced, respectively. T-DNA insertion and expression of the transgene were confirmed from most of the transgenic plants by polymerase chain reaction (PCR), quantitative real-time PCR (qPCR), reverse transcription PCR (RT-PCR), and Southern blot analysis. The fatty acid composition of soybean seeds was analyzed by gas chromatography. The 18:3 content in the transgenic generation T1 seeds was increased 7-fold in Pß-con:PfFAD3-1, 4-fold in Pphas : PfFAD3-1, and 1.6-fold in P35S:PfFAD3-1 compared to the 18:3 content in soybean "Kwangankong". The increased content of 18:3 in the Pß-con:PfFAD3-1 soybean (T1) resulted in a 52.6% increase in total fatty acids, with a larger decrease in 18:1 content than 18:2 content. The increase in 18:3 content was also maintained and reached 42% in the Pphas : PfFAD3-1 transgenic generation T2. Investigations of the agronomic traits of 12 Pß-con:PfFAD3-1 transgenic lines (T1) revealed that plant height, number of branches, nodes, pods, total seeds, and total seed weight were significantly higher in several transgenic lines than those in non-transgenic soybean. Especially, an increase in seed size was observed upon expression of the PfFAD3-1 gene with the ß-conglycinin promoter, and 6%-14% higher seed lengths were measured from the transgenic lines.

ORESARA15 Acts Synergistically with ANGUSTIFOLIA3 and Separately from AINTEGUMENTA to Promote Cell Proliferation during Leaf Growth.

Developing leaves undergo sequential coordinated cell proliferation and cell expansion to determine their final size and shape. Although several important regulators of cell proliferation have been reported, the gene network regulating leaf developmental processes remains unclear. Previously, we showed that ORESARA15 (ORE15) positively regulates the rate and duration of cell proliferation by promoting the expression of direct targets, GROWTH-REGULATING FACTOR (GRF) transcription factors, during leaf growth. In the current study, we examined the spatiotemporal patterns of ORE15 expression and determined that ORE15 expression partially overlapped with AN3/GIF1 and ANT expression along the midvein in the proximal region of the leaf blade in young leaves. Genetic analysis revealed that ORE15 may function synergistically with AN3 to control leaf growth as a positive regulator of cell proliferation. Our molecular and genetic studies are the first to suggest the importance of functional redundancies between ORE15 and AN3, and between AN3 and ANT in cell proliferation regulatory pathway during leaf growth.

ORESARA15, a PLATZ transcription factor, mediates leaf growth and senescence in Arabidopsis.

Plant leaves undergo a series of developmental changes from leaf primordium initiation through growth and maturation to senescence throughout their life span. Although the mechanisms underlying leaf senescence have been intensively elucidated, our knowledge of the interrelationship between early leaf development and senescence is still fragmentary. We isolated the oresara15-1Dominant (ore15-1D) mutant, which had an extended leaf longevity and an enlarged leaf size, from activation-tagged lines of Arabidopsis. Plasmid rescue identified that ORE15 encodes a PLANT A/T-RICH SEQUENCE- AND ZINC-BINDING PROTEIN family transcription factor. Phenotypes of ore15-1D and ore15-2, a loss-of-function mutant, were evaluated through physiological and anatomical analyses. Microarray, quantitative reverse transcription polymerase chain reaction, and chromatin immunoprecipitation as well as genetic analysis were employed to reveal the molecular mechanism of ORE15 in the regulation of leaf growth and senescence. ORE15 enhanced leaf growth by promoting the rate and duration of cell proliferation in the earlier stage and suppressed leaf senescence in the later stage by modulating the GROWTH-REGULATING FACTOR (GRF)/GRF-INTERACTING FACTOR regulatory pathway. Our study highlighted a molecular conjunction through ORE15 between growth and senescence, which are two temporally separate developmental processes during leaf life span.

Poststroke emotional disturbances and a tryptophan hydroxylase 2 gene polymorphism.

Objectives: Emotional dysfunction is a common finding in stroke patients. Despite reports on serotonergic involvement in the etiology of poststroke emotional dysfunction (PSED), the role of serotonin synthesizing tryptophan hydroxylase 2 (TPH2) genes in the development of PSED remains unclear. Methods: Genotyping of TPH2 rs4641528 and rs10879355 was performed from genomic DNA of 383 stroke patients collected previously and stored at -70°C. Potential associations between TPH2 genes and poststroke depression (PSD), poststroke emotional incontinence (PSEI), and poststroke anger proneness (PSAP) were investigated 3 months poststroke. Results: Among the 383 patients, 69 (18%) had PSD, 41 (11%) had PSEI, and 93 (24%) had PSAP. The TPH2 rs4641528 genotype frequencies differed significantly between patients with and without either PSD or PSEI, although no significant differences were found between the patients with and without PSAP. In multiple logistic regression analysis, PSD was related to the National Institutes of Health Stroke Scale (NIHSS) score at admission (95% confidence interval [CI]: 1.047-1.230, p < .01), modified Rankin scale score at 3 months (95% CI: 0.135-0.848, p < .05), and TPH2 rs4641528 C allele (95% CI: 1.039-5.631, p < .05), whereas PSEI was associated only with the NIHSS score at admission (95% CI: 1.053-1.259, p < .01) and the TPH2 rs4641528 C allele (95% CI: 1.029-11.678, p < .05). Conclusions: Our findings suggest that the TPH2 rs4641528 C allele may play a role in the pathogenesis of PSD and PSEI but not PSAP in Korean stroke patients.

The predictive role of health-promoting behaviours and perceived stress in aneurysmal rupture.

AIMS AND OBJECTIVES: To examine the roles of two modifiable factors-health-promoting behaviours and perceived stress-in predicting aneurysmal rupture. BACKGROUND: Unruptured intracranial aneurysm detection produces significant stress and anxiety in patients because of the risk of rupture. Compared to nonmodifiable risk factors for rupture such as age, gender and aneurysm size/location, less attention has been given to modifiable risk factors. Two modifiable factors, health-promoting behaviours and perceived stress, have hardly been examined as potential predictors of rupture. DESIGN: This study used a cross-sectional design. METHODS: We assessed 155 patients with intracranial aneurysms-that is, subarachnoid haemorrhage (n = 77) or unruptured intracranial aneurysm (n = 78)-to examine (i) baseline characteristics (patient and aneurysmal factors), (ii) health-related factors (lifestyle habits and health-promoting behaviour) and (iii) perceived stress levels (psychological stress and physical stress). Patient records provided medical histories and aneurysmal factors; other data were collected using a structured questionnaire addressing lifestyle habits, the Health-Promoting Lifestyle Profile-II to measure health-promoting behaviour and the Perceived Stress Questionnaire to measure perceived-psychological stress and perceived-physical stress levels. RESULTS: Bivariate analysis indicated that aneurysm rupture risk was associated with female gender, aneurysm size/location, defecation frequency, hyperlipidaemia, sedentary time, low Health-Promoting Lifestyle Profile-II mean scores and high perceived-psychological stress scores. After adjusting for known risk factors, the mean Health-Promoting Lifestyle Profile-II and perceived-psychological stress scores remained robust predictors of rupture. Furthermore, known risk factors combined with these scores had greater predictive power than known risk factors alone. CONCLUSION: Health-promoting behaviour and psychological stress are promising modifiable factors for reducing risk of aneurysmal rupture. RELEVANCE TO CLINICAL PRACTICE: Our findings may stimulate greater understanding of mechanisms underlying aneurysmal rupture and suggest practical strategies for nurses to employ in optimising conservative management of rupture risk by teaching patients how to modify their risk. Both health-promoting behaviour and perceived stress should be addressed when designing preventive nursing interventions for patients with unruptured intracranial aneurysm.

Use of a Yeast tRNase Killer Toxin to Diagnose Kti12 Motifs Required for tRNA Modification by Elongator.

Saccharomyces cerevisiae cells are killed by zymocin, a tRNase ribotoxin complex from Kluyveromyces lactis, which cleaves anticodons and inhibits protein synthesis. Zymocin's action requires specific chemical modification of uridine bases in the anticodon wobble position (U34) by the Elongator complex (Elp1-Elp6). Hence, loss of anticodon modification in mutants lacking Elongator or related KTI (K. lactis Toxin Insensitive) genes protects against tRNA cleavage and confers resistance to the toxin. Here, we show that zymocin can be used as a tool to genetically analyse KTI12, a gene previously shown to code for an Elongator partner protein. From a kti12 mutant pool of zymocin survivors, we identify motifs in Kti12 that are functionally directly coupled to Elongator activity. In addition, shared requirement of U34 modifications for nonsense and missense tRNA suppression (SUP4; SOE1) strongly suggests that Kti12 and Elongator cooperate to assure proper tRNA functioning. We show that the Kti12 motifs are conserved in plant ortholog DRL1/ELO4 from Arabidopsis thaliana and seem to be involved in binding of cofactors (e.g., nucleotides, calmodulin). Elongator interaction defects triggered by mutations in these motifs correlate with phenotypes typical for loss of U34 modification. Thus, tRNA modification by Elongator appears to require physical contact with Kti12, and our preliminary data suggest that metabolic signals may affect proper communication between them.

Associations of VCAM-1 gene polymorphisms with obesity and inflammation markers.

OBJECTIVE: Among the inflammatory mediators involved in the pathogenesis of obesity, cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) stand out. The aim of this study was to investigate the associations of ICAM-1 and VCAM-1 gene variants with obesity and to investigate the associations between these genetic polymorphisms and CRP, UA, and WBC count. METHOD: Four SNPs of the VCAM-1 gene (rs3176860, rs2392221, rs3917010 and rs3176879) and two SNPs of the ICAM-1 gene (rs281432 and rs5498) were analyzed in 181 control (18 < BMI < 23) and 144 obese (BMI ≥ 25) subjects. The SNPs were genotyped by direct sequencing. RESULTS: In allele frequency analysis, the G allelic frequency of rs3176860 in the VCAM-1 gene was lower in the obese group (30.9%) than in the controls (41.2%) (P = 0.007). The C allelic frequency of rs3917010 was lower in the obese group (18.1%) than in the control (25.1%) (P = 0.03). In the haplotype analysis of VCAM-1 gene, the ht1 (ACA) was higher and ht2 (GCC) was lower in the obese subjects than in the controls (P = 0.0057 and P = 0.037, respectively). In the obese group, participants carrying the G allele of rs3176860 of the VCAM-1 gene showed a higher percentage of segmented neutrophils and CRP levels than those carrying only the A allele (P = 0.028 and P = 0.042, respectively). CONCLUSIONS: The results of this study suggest that VCAM-1 gene variants may be related to obesity and inflammatory markers in the Korean population.

Post-Stroke Fatigue May Be Associated with the Promoter Region of a Monoamine Oxidase A Gene Polymorphism.

BACKGROUND: Post-stroke fatigue (PSF) is a common sequela of stroke. Despite reports of serotonergic involvement in the etiology of PSF, the potential contribution of serotonergic genes in the development of PSF needs to be investigated. METHODS: A total of 373 patients, who experienced ischemic stroke for PSF, were evaluated 3 months after the stroke. PSF was assessed using the Fatigue Severity Scale. The genomic DNA collected and stored in a -70°C freezer was genotyped for 6 polymorphisms in genes associated with serotonin synthesis (tryptophan hydroxylase 1 (TPH1) A218C, TPH2 rs10879355, and TPH2 rs4641528), transport (the promoter region of the serotonin transporter protein), and catabolism (the 30-bp functional variable number tandem repeat) polymorphism in the promoter region of monoamine oxidase A (MAO-A). RESULTS: Among the 373 patients, 164 (44%) had PSF. All patients were ethnic Koreans. Of the 6 polymorphisms examined, only one marker, that is, low-activity MAO-A was associated with PSF (p < 0.05) in female patients. Multiple logistic regression analyses showed that post-stroke depression (PSD; 95% CI 1.561-14.323, p = 0.006) and low MAO-A activity (95% CI 0.166-0.722, p = 0.005) were factors associated with PSF in female patients, whereas only PSD (95% CI 5.511-65.269, p = 0.000) was associated with PSF in male patients. CONCLUSIONS: Our findings suggest that PSF may be associated with a genetic polymorphism involving MAO-A, at least in female stroke patients.

Arabidopsis thaliana homeobox 12 (ATHB12), a homeodomain-leucine zipper protein, regulates leaf growth by promoting cell expansion and endoreduplication.

Arabidopsis thaliana homeobox 12 (ATHB12), a homeodomain-leucine zipper class I (HD-Zip I) gene, is highly expressed in leaves and stems, and induced by abiotic stresses, but its role in development remains obscure. To understand its function during plant development, we studied the effects of loss and gain of function. Expression of ATHB12 fused to the EAR-motif repression domain (SRDX) - P35 S ::ATHB12SRDX (A12SRDX) and PATHB 12 ::ATHB12SRDX - slowed both leaf and root growth, while the growth of ATHB12-overexpressing seedlings (A12OX) was accelerated. Microscopic examination revealed changes in the size and number of leaf cells. Ploidy was reduced in A12SRDX plants, accompanied by decreased cell expansion and increased cell numbers. By contrast, cell size was increased in A12OX plants, along with increased ploidy and elevated expression of cell cycle switch 52s (CCS52s), which are positive regulators of endoreduplication, indicating that ATHB12 promotes leaf cell expansion and endoreduplication. Overexpression of ATHB12 led to decreased phosphorylation of Arabidopsis thaliana ribosomal protein S6 (AtRPS6), a regulator of cell growth. In addition, induction of ATHB12 in the presence of cycloheximide increased the expression of several genes related to cell expansion, such as EXPANSIN A10 (EXPA10) and DWARF4 (DWF4). Our findings strongly suggest that ATHB12 acts as a positive regulator of endoreduplication and cell growth during leaf development.

Comparative analysis of the conserved functions of Arabidopsis DRL1 and yeast KTI12.

Patterning of the polar axis during the early leaf developmental stage is established by cell-to-cell communication between the shoot apical meristem (SAM) and the leaf primordia. In a previous study, we showed that the DRL1 gene, which encodes a homolog of the Elongator-associated protein KTI12 of yeast, acts as a positive regulator of adaxial leaf patterning and shoot meristem activity. To determine the evolutionally conserved functions of DRL1, we performed a comparison of the deduced amino acid sequence of DRL1 and its yeast homolog, KTI12, and found that while overall homology was low, well-conserved domains were presented. DRL1 contained two conserved plant-specific domains. Expression of the DRL1 gene in a yeast KTI12-deficient yeast mutant suppressed the growth retardation phenotype, but did not rescue the caffeine sensitivity, indicating that the role of Arabidopsis Elongator-associated protein is partially conserved with yeast KTI12, but may have changed between yeast and plants in response to caffeine during the course of evolution. In addition, elevated expression of DRL1 gene triggered zymocin sensitivity, while overexpression of KTI12 maintained zymocin resistance, indicating that the function of Arabidopsis DRL1 may not overlap with yeast KTI12 with regards to toxin sensitivity. In this study, expression analysis showed that class-I KNOX genes were downregulated in the shoot apex, and that YAB and KAN were upregulated in leaves of the Arabidopsis drl1-101 mutant. Our results provide insight into the communication network between the SAM and leaf primordia required for the establishment of leaf polarity by mediating histone acetylation or through other mechanisms.

TPH gene polymorphisms are associated with disease perception and quality of life in women with irritable bowel syndrome.

The aims of this exploratory study were to examine whether tryptophan hydroxylase (TPH) gene polymorphisms are associated with psychosocial factors in women with irritable bowel syndrome (IBS). TPH is the rate-limiting enzyme in the biosynthesis of serotonin and has two isoforms, TPH1 and TPH2. Four single nucleotide polymorphisms (SNPs) in the TPH1 gene and one SNP in the TPH2 gene were selected based on previous studies investigating associations between these SNPs and psychiatric or behavioral disorders. One hundred ninety-nine Caucasian women with IBS were included. Results of univariate analysis showed no association between TPH1and TPH2 gene SNPs and current level of psychological distress or psychiatric illness. However, TPH1 gene SNPs were associated with IBS-related cognitions (rs4537731 and rs21105) and quality of life (rs684302 and rs1800532), in particular the mental health and energy subscales. These associations were independent of the subjects' levels of gastrointestinal symptoms. These results suggest that patients' perception of their illness, and of the impact it has on their lives, may be subject to genetic influences, in this case sequence variants in TPH1. However, caution should be used in interpreting these results given the large number of hypothesis tests performed in this exploratory hypothesis-generating study, and the results should be considered tentative until confirmed in an independent sample.

Update on irritable bowel syndrome program of research.

PURPOSE: This article provides an update and overview of a nursing research program focused on understanding the pathophysiology and management of irritable bowel syndrome (IBS). METHODS: This review includes English language papers from the United States, Europe, and Asia (e.g., South Korea) from 1999 to 2013. We addressed IBS as a health problem, emerging etiologies, diagnostic and treatment approaches and the importance of a biopsychosocial model. RESULTS: IBS is a chronic, functional gastrointestinal disorder characterized by recurrent episodes of abdominal pain and alterations in bowel habit (diarrhea, constipation, mixed). It is a condition for which adults, particularly women ages 20-45, seek health care services in both the United States and South Korea. Clinically, nurses play key roles in symptom prevention and management including designing and implementing approaches to enhance the patients' self-management strategies. Multiple mechanisms are believed to participate in the development and maintenance of IBS symptoms including autonomic nervous system dysregulation, intestinal inflammation, intestinal dysbiosis, dietary intolerances, alterations in emotion regulation, heightened visceral pain sensitivity, hypothalamic-pituitary-adrenal dysregulation, and dysmotility. Because IBS tends to occur in families, genetic factors may also contribute to the pathophysiology. Patients with IBS often report a number of co-morbid disorders and/or symptoms including poor sleep. CONCLUSION: The key to planning effective management strategies is to understand the heterogeneity of this disorder. Interventions for IBS include non-pharmacological strategies such as cognitive behavior therapy, relaxation strategies, and exclusion diets.

Kip-related protein 3 is required for control of endoreduplication in the shoot apical meristem and leaves of Arabidopsis.

The cell cycle plays an important role in the development and adaptation of multicellular organisms; specifically, it allows them to optimally adjust their architecture in response to environmental changes. Kip-related proteins (KRPs) are important negative regulators of cyclin-dependent kinases (CDKs), which positively control the cell cycle during plant development. The Arabidopsis genome possesses seven KRP genes with low sequence similarity and distinct expression patterns; however, why Arabidopsis needs seven KRP genes and how these genes function in cell cycle regulation are unknown. Here, we focused on the characterization of KRP3, which was found to have unique functions in the shoot apical meristem (SAM) and leaves. KRP3 protein was localized to the SAM, including the ground meristem and vascular tissues in the ground part of the SAM and cotyledons. In addition, KRP3 protein was stabilized when treated with MG132, an inhibitor of the 26S proteasome, indicating that the protein may be regulated by 26S proteasome-mediated protein degradation. KRP3-overexpressing (KRP3 OE) transgenic plants showed reduced organ size, serrated leaves, and reduced fertility. Interestingly, the KRP3 OE transgenic plants showed a significant reduction in the size of the SAM with alterations in cell arrangement. In addition, compared to the wild type, the KRP3 OE transgenic plants had a higher DNA ploidy level in the SAM and leaves. Taken together, our data suggest that KRP3 plays important regulatory roles in the cell cycle and endoreduplication in the SAM and leaves.

Conditioned media obtained from human outer root sheath follicular keratinocyte culture activates signalling pathways that contribute to maintenance of hair-inducing capacity and increases trichogenicity of cultured dermal cells.

Findings from recent studies have demonstrated that hair-inducing capacity (trichogenicity) of cultured dermal cells can be maintained by addition of conditioned media obtained from culture of epidermal keratinocytes. In this study, we investigated the question of whether treatment with human follicular keratinocyte-conditioned media (FKCM) can result in activation of signalling pathways that contribute to trichogenicity and increase the trichogenicity of cultured dermal cells. Through conduct of hair reconstitution assays, we observed that treatment of cells with FKCM resulted in induction of a greater number of hair follicles, compared with control cells. Treatment of dermal cells with FKCM resulted in the activation of BMP and ß-catenin signalling pathways. In addition, higher levels of IGFBP-7, IL-8, OPG and uPA were observed in FKCM. Altogether, our data suggest that a patient's own FKCM would be ideal for expansion of the patient's own follicular dermal cells for cell therapy for treatment of hair loss.

Comprehensive self-management reduces the negative impact of irritable bowel syndrome symptoms on sexual functioning.

BACKGROUND: Women with irritable bowel syndrome (IBS) report sexual dysfunction. Comprehensive self-management (CSM) intervention has been shown to reduce gastrointestinal, psychological, and somatic symptoms in IBS women. Whether this intervention also reduces sexual dysfunction is not known. AIMS: We sought to compare demographic and clinical factors in IBS women with and without sexual dysfunction as defined by the Arizona sexual experiences scale (ASEX) and to test the effects of CSM treatment on sexual dysfunction scores and on the sexual relations subscale of an IBS quality of life (IBSQOL) scale which measures the effect of IBS on sexual QOL. METHODS: IBS (Rome II) women enrolled in a randomized clinical trial of CSM treatment were characterized as having sexual dysfunction (N = 89) or not (N = 86) at baseline based on ASEX criteria. Baseline characteristics and symptoms were compared between the two groups. Post-intervention changes were compared between the CSM and the usual care arms of the randomized trial. RESULTS: Women meeting ASEX criteria for sexual dysfunction were older, had higher lifetime depression and antidepressant use, more primary care/MD visits, fewer mental healthcare visits, and greater sleep disturbance than those without sexual dysfunction. No significant group differences in gastrointestinal or somatic symptoms were observed. Compared with usual care treatment, CSM increased sexual QOL scores and had a weaker effect on ASEX scores. CONCLUSIONS: Severity of IBS symptoms at baseline did not differ between IBS women with or without sexual dysfunction. The CSM intervention can reduce the effect of IBS on sexual QOL.