RefZ Facilitates the Switch from Medial to Polar Division during Spore Formation in Bacillus subtilis

During sporulation, Bacillus subtilis redeploys the division protein FtsZ from midcell to the cell poles, ultimately generating an asymmetric septum. Here, we describe a sporulation-induced protein, RefZ, that facilitates the switch from a medial to a polar FtsZ ring placement. The artificial expression of RefZ during vegetative growth converts FtsZ rings into FtsZ spirals, arcs, and foci, leading to filamentation and lysis. Mutations in FtsZ specifically suppress RefZ-dependent division inhibition, suggesting that RefZ may target FtsZ. During sporulation, cells lacking RefZ are delayed in polar FtsZ ring formation, spending more time in the medial and transition stages of FtsZ ring assembly. A RefZ-green fluorescent protein (GFP) fusion localizes in weak polar foci at the onset of sporulation and as a brighter midcell focus at the time of polar division. RefZ has a TetR DNA binding motif, and point mutations in the putative recognition helix disrupt focus formation and abrogate cell division inhibition. Finally, chromatin immunoprecipitation assays identified sites of RefZ enrichment in the origin region and near the terminus. Collectively, these data support a model in which RefZ helps promote the switch from medial to polar division and is guided by the organization of the chromosome. Models in which RefZ acts as an activator of FtsZ ring assembly near the cell poles or as an inhibitor of the transient medial ring at midcell are discussed.

Clinical Predictors Associated With Duration of Repetitive Transcranial Magnetic Stimulation Treatment for Remission in Bipolar Depression A Naturalistic Study

Repetitive transcranial magnetic stimulation (rTMS) has been widely tested and shown to be effective for unipolar depression. Although it has also been investigated for bipolar depression (BD), there are only few rTMS studies with BD. Here, we investigated 56 patients with BD who received rTMS treatment until remission (defined as Hamilton Depression Rating Scores <= 7). We used simple and multiple logistic regressions to identify clinical and demographic predictors associated with duration of treatment (defined as <15 vs. >15 rTMS sessions). Age, refractoriness, number of prior depressive episodes, and severe depression at baseline were associated with a longer rTMS treatment. In the multivariate analysis, refractoriness (likelihood ratio (LR) = 4.33; p < 0.01) and baseline severity (LR = 0.18, p < 0.01) remained significant predictors. Our preliminary study showed that, in remitted patients, refractoriness and severity of index episode are associated with the need of a longer rTMS treatment; providing preliminary evidence of important factors associated with rTMS parameters adjustment.

A cyclic bipolar wind in the interacting binary V 393 Scorpii

V393 Scorpii is a double periodic variable characterized by a relatively stable non-orbital photometric cycle of 253 d. Mennickent et al. argue for the presence of a massive optically thick disc around the more massive B-type component and describe the evolutionary stage of the system. In this paper, we analyse the behaviour of the main spectroscopic optical lines during the long non-orbital photometric cycle. We study the radial velocity of the donor determining its orbital elements and find a small but significant orbital eccentricity (e = 0.04). The donor spectral features are modelled and removed from the spectrum at every observing epoch using the light-curve model given by Mennickent et al. We find that the line emission is larger during eclipses and mostly comes from a bipolar wind. We also find that the long cycle is explained in terms of a modulation of the wind strength; the wind has a larger line and continuum emissivity at the high state. We report the discovery of highly variable chromospheric emission in the donor, as revealed by the Doppler maps of the emission lines Mg II 4481 and C I 6588. We discuss notable and some novel spectroscopic features like discrete absorption components, especially visible at blue depressed O I 7773 absorption wings during the second half-cycle, Balmer double emission with V/R curves showing 'Z-type' and 'S-type' excursions around secondary and main eclipses, respectively, and H beta emission wings extending up to +/- 2000 km s(-1). We also discuss possible causes for these phenomena and for their modulations with the long cycle.

THE IMPLICATIONS OF A PSYCHOEDUCATION GROUP ON THE EVERYDAY LIVES OF INDIVIDUALS WITH BIPOLAR AFFECTIVE DISORDER

There is growing evidence that the course of Bipolar Affective Disorder (BAD) can be altered by psychotherapeutic approaches, such as Psychoeducation. Therefore, this study was performed with the objective of identifying the implications of a Psychoeducation group on the everyday lives of individuals with BAD. To do this, the authors chose to perform a qualitative case study. Participants included twelve individuals with BAD who had attended at least six meetings of the Psychoeducation Group held at the Sao Jose do Rio Preto Faculty of Medicine (FAMERP). Semi-structured interviews were performed, which were recorded and then transcribed and subjected to Thematic Analysis. The present study showed that the referred group experience promoted the individuals' knowledge acquisition; their awareness regarding the disease and adherence to treatment; their making positive changes in life; the possibility of helping other patients to benefit from the knowledge learned in the group; and their awareness regarding other realities and coping strategies, obtained by exchanging experiences with other participants.

DivIVA-Mediated Polar Localization of ComN, a Posttranscriptional Regulator of Bacillus subtilis

ComN (YrzD) is a small, 98-amino-acid protein recently shown to be involved in the posttranscriptional control of the late competence comE operon in Bacillus subtilis. We show here that ComN localizes to the division site and cell poles in a DivIVA-dependent fashion. Yeast two-hybrid and glutathione S-transferase pulldown experiments showed that ComN interacts directly with DivIVA. ComN is not essential for the polar assembly of the core competence DNA uptake machinery. Nevertheless, polar localization of ComN should play some role in competence acquisition because delocalization of ComN leads to a small reduction in competence efficiency. We found that ComN promotes the accumulation of its target comE mRNA to septal and polar sites. Thus, we speculate that localized translation of ComE proteins may be required for efficient competence development. Our results underscore the versatility of DivIVA as a promoter of the differentiation of bacterial poles and demonstrate that the repertoire of polarly localized molecules in B. subtilis is broad, including a regulator of gene expression and its target mRNA. Moreover, our findings suggest that mRNA localization may play a role in the subcellular organization of bacteria.

Discourse and bipolar disorder: Narrative therapy on northeast Brazil

Background: The expression 'bipolar disorder' refers to any of several psychological disorders of mood that alternate episodes of depression and mania. Also called manic depression or manic-depressive illness, it is a relatively common but unknown pathology that brings some stigmas for patients and provokes deleterious effects for their lives. This research aimed to comprehend actions, behaviors and emotions involved with bipolar disorder, through narratives of patient's personal and familiar histories. Methods: We surveyed 30 patients from a psychiatric service located in Aparecida, Paraiba, Brazil. Selected patients had bipolar disorder according to DSM-IV. For data collection, we used non-structured interview, approaching specific aspects related to bipolar disorder. Quantitative and qualitative analysis were done and Hamilton Rating Scale for Depression (HAMD) was used. Results: Most of patients presented depressive actions associated with moderate euphoria. 11 of them related familiar history of psychopathology. Mania and hippomania were prevalent on male gender, while psychotic symptoms overlay ate female. Conclusion: Patients lack a translation of behavioral and temperamental processes to minimize harm caused to their lives.

Associations among genotype, clinical phenotype, and intracellular localization of trafficking proteins in ARC syndrome

Arthrogryposisrenal dysfunctioncholestasis (ARC) syndrome is a rare autosomal recessive multisystem disorder caused by mutations in vacuolar protein sorting 33 homologue B (VPS33B) and VPS33B interacting protein, apicalbasolateral polarity regulator (VIPAR). Cardinal features of ARC include congenital joint contractures, renal tubular dysfunction, cholestasis, severe failure to thrive, ichthyosis, and a defect in platelet alpha-granule biogenesis. Most patients with ARC do not survive past the first year of life. We report two patients presenting with a mild ARC phenotype, now 5.5 and 3.5 years old. Both patients were compound heterozygotes with the novel VPS33B donor splice-site mutation c.1225+5G>C in common. Immunoblotting and complementary DNA analysis suggest expression of a shorter VPS33B transcript, and cell-based assays show that c.1225+5G>C VPS33B mutant retains some ability to interact with VIPAR (and thus partial wild-type function). This study provides the first evidence of genotypephenotype correlation in ARC and suggests that VPS33B c.1225+5G>C mutation predicts a mild ARC phenotype. We have established an interactive online database for ARC (https://grenada.lumc.nl/LOVD2/ARC) comprising all known variants in VPS33B and VIPAR. Also included in the database are 15 novel pathogenic variants in VPS33B and five in VIPAR. Hum Mutat 33:16561664, 2012. (c) 2012 Wiley Periodicals, Inc.

COMT Met (158) modulates facial emotion recognition in bipolar I disorder mood episodes

Background: One of the many cognitive deficits reported in bipolar disorder (BD) patients is facial emotion recognition (FER), which has recently been associated with dopaminergic catabolism. Catechol-O-methyltransferase (COMT) is one of the main enzymes involved in the metabolic degradation of dopamine (DA) in the prefrontal cortex (PFC). The COMT gene polymorphism rs4680 (Val(158)Met) Met allele is associated with decreased activity of this enzyme in healthy controls. The objective of this study was to evaluate the influence of Val(158)Met on FER during manic and depressive episodes in BD patients and in healthy controls. Materials and methods: 64 BD type I patients (39 in manic and 25 in depressive episodes) and 75 healthy controls were genotyped for COMT rs4680 and assessed for FER using the Ekman 60 Faces (EK60) and Emotion Hexagon (Hx) tests. Results: Bipolar manic patients carrying the Met allele recognized fewer surprised faces, while depressed patients with the Met allele recognized fewer "angry" and "happy" faces. Healthy homozygous subjects with the Met allele had higher FER scores on the Hx total score, as well as on "disgust" and "angry" faces than other genotypes. Conclusion: This is the first study suggesting that COMT rs4680 modulates FER differently during BD episodes and in healthy controls. This provides evidence that PFC DA is part of the neurobiological mechanisms of social cognition. Further studies on other COMT polymorphisms that include euthymic BD patients are warranted. ClinicalTrials.gov Identifier: NCT00969. (C) 2011 Elsevier B.V. All rights reserved.

Neither bipolar nor obsessive-compulsive disorder: compulsive buyers are impulsive acquirers

Introduction: Compulsive buying (CB) is currently classified as an impulse control disorder (ICD) not otherwise classified. Compulsive buying prevalence is estimated at around 5% of the general population. There is controversy about whether CB should be classified as an ICD, a subsyndromal bipolar disorder (BD), or an obsessive-compulsive disorder (OCD) akin to a hoarding syndrome. To further investigate the appropriate classification of CB, we compared patients with CB, BD, and OCD for impulsivity, affective instability, hoarding, and other OCD symptoms. Method: Eighty outpatients (24 CB, 21 BD, and 35 OCD) who were neither manic nor hypomanic were asked to fill out self-report questionnaires. Results: Compulsive buying patients scored significantly higher on all impulsivity measures and on acquisition but not on the hoarding subdimensions of clutter and "difficulty discarding." Patients with BD scored higher on the mania dimension from the Structured Clinical Interview for Mood Spectrum scale. Patients with OCD scored higher on obsessive-compulsive symptoms and, particularly, higher on the contamination/washing and checking dimensions from the Padua Inventory; however, they did not score higher on any hoarding dimension. A discriminant model built with these variables correctly classified patients with CB (79%), BD (71%), and OCD (77%). Conclusion: Patients with CB came out as impulsive acquirers, resembling ICD- rather than BD- or OCD-related disorders. Manic symptoms were distinctive of patients with BD. Hoarding symptoms other than acquisition were not particularly associated with any diagnostic group. (C) 2012 Elsevier Inc. All rights reserved.

Tamoxifen Subcellular Localization; Observation of Cell-Specific Cytotoxicity Enhancement by Inhibition of Mitochondrial ETC Complexes I and III

Recently, a nongenomic cytotoxic component of the chemotherapeutic agent tamoxifen (TAM) has been identified that predominantly triggers mitochondrial events. The present study delineates the intracellular fate of TAM and studies its interaction with a spectrum of cell homeostasis modulators primarily relevant to mitochondria. The subcellular localization of TAM was assessed by confocal fluorescence microscopy. The effect of the modulators on TAM cytotoxicity was assessed by standard MTT assays. Our findings show that in estrogen receptor positive MCF7 breast adenocarcinoma cells and DU145 human prostate cancer cells, TAM largely accumulates in the mitochondria and endoplasmic reticulum, but not lysosomes. Our results further demonstrate that in MCF7, but not in DU145 cells, mitochondrial electron transport chain complex I and III inhibitors exacerbate TAM toxicity with an order of potency of myxothiazol = stigmatellin > rotenone > antimycin A, suggesting a cell-specific cytotoxic interplay between mitochondrial complex I and III function and TAM action.

Site localization of Cd impurities in sapphire

By combining first-principles electronic structure calculations and existing time-differential gamma-gamma perturbed-angular-correlation experiments we studied the site localization, the local environment, and the electronic structure of Cd impurities in sapphire (alpha-Al2O3) single crystals in different charged states. The ab initio calculations were performed with the full-potential augmented plane wave plus local orbitals method and the projector augmented wave method. Comparing the calculated electric-field-gradient tensor at the Cd nuclei in the alpha-Al2O3 host lattice and the corresponding available experimental values, we have seen that it is equally possible for Cd to replace an Al atom (in a negative charge state) or to be placed in an interstitial site (in a neutral charge state). To finally address the issue of the Cd impurity localization, we performed formation energy calculations. These results have shown that Cd placed in the substitutional Al site, in the negatively charged state, is the most probable configuration.

Use of Large-volume Cone-Beam Computed Tomography in Identification and Localization of Horizontal Root Fracture in the Presence and Absence of Intracanal Metallic Post

Introduction: The objective of the study was to evaluate the ability of large-volume cone-beam computed tomography (CBCT) to detect horizontal root fracture and to test the influence of a metallic post. Methods: Through the examination of 40 teeth by large-volume CBCT (20-cm height and 15-cm diameter cylinder) at 0.2-mm voxel resolution, 2 observers analyzed the samples for the presence and localization of horizontal root fracture. Results: The values of accuracy in the groups that had no metallic post ranged from 33%-68%, whereas for the samples with the metallic post, values showed a wide variation (38%-83%). Intraobserver agreement showed no statistically significant difference between the groups with/without metallic post; both ranged from very weak to weak (kappa, 0.09-0.369). Conclusions: The low accuracy and low intraobserver and interobserver agreement reflect the difficulty in performing an adequate diagnosis of horizontal root fractures through a large-volume CBCT by using a small voxel reconstruction. (J Endod 2012;38:856-859)

Impact of sunlight on the age of onset of bipolar disorder

Bauer M, Glenn T, Alda M, Andreassen OA, Ardau R, Bellivier F, Berk M, Bjella TD, Bossini L, Del Zompo M, Dodd S, Fagiolini A, Frye MA, Gonzalez-Pinto A, Henry C, Kapczinski F, Kliwicki S, Konig B, Kunz M, Lafer B, Lopez-Jaramillo C, Manchia M, Marsh W, Martinez-Cengotitabengoa M, Melle I, Morken G, Munoz R, Nery FG, ODonovan C, Pfennig A, Quiroz D, Rasgon N, Reif A, Rybakowski J, Sagduyu K, Simhandl C, Torrent C, Vieta E, Zetin M, Whybrow PC. Impact of sunlight on the age of onset of bipolar disorder. Bipolar Disord 2012: 14: 654663. (c) 2012 The Authors. Journal compilation (c) 2012 John Wiley & Sons A/S. Objective: Although bipolar disorder has high heritability, the onset occurs during several decades of life, suggesting that social and environmental factors may have considerable influence on disease onset. This study examined the association between the age of onset and sunlight at the location of onset. Method: Data were obtained from 2414 patients with a diagnosis of bipolar I disorder, according to DSM-IV criteria. Data were collected at 24 sites in 13 countries spanning latitudes 6.3 to 63.4 degrees from the equator, including data from both hemispheres. The age of onset and location of onset were obtained retrospectively, from patient records and/or direct interviews. Solar insolation data, or the amount of electromagnetic energy striking the surface of the earth, were obtained from the NASA Surface Meteorology and Solar Energy (SSE) database for each location of onset. Results: The larger the maximum monthly increase in solar insolation at the location of onset, the younger the age of onset (coefficient= -4.724, 95% CI: -8.124 to -1.323, p = 0.006), controlling for each countrys median age. The maximum monthly increase in solar insolation occurred in springtime. No relationships were found between the age of onset and latitude, yearly total solar insolation, and the maximum monthly decrease in solar insolation. The largest maximum monthly increases in solar insolation occurred in diverse environments, including Norway, arid areas in California, and Chile. Conclusion: The large maximum monthly increase in sunlight in springtime may have an important influence on the onset of bipolar disorder.

Impact of comorbid migraine on the clinical course of bipolar disorder

Background: Recent evidence suggests an association between migraine and bipolar disorder (BD), although the impact of this association in the clinical course of BD is relatively unknown. Objective: This study aimed to compare 2 groups of individuals with BD (with vs without comorbid migraine) and evaluate differences in severity of clinical course. Methods: Three hundred thirty-nine adults with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition defined bipolar or II disorder were enrolled and divided into 2 groups: with and without comorbid migraine. Demographic and clinical data were obtained using standardized interviews. Results: Patients with comorbid migraines had more mood episodes, especially those with depressive polarity. In addition, comorbid migraine was associated with a higher prevalence of psychiatric and general medical comorbidities. Differences between the 2 groups in number of lifetime hospitalizations for depression/mania, rates of rapid cycling, and history of suicide attempts were not observed after Bonferroni correction. Conclusions: Comorbid migraine seems to be associated with poor outcomes in BD. Additional studies should be conducted to investigate shared vulnerabilities and pathophysiologic mechanisms as well as treatment optimization of both illnesses. (C) 2012 Elsevier Inc. All rights reserved.

Burden of maternal bipolar disorder on at-risk offspring: A controlled study on family planning and maternal care

Introduction: Bipolar disorder (BD) is a highly incapacitating disease typically associated with high rates of familial dysfunction. Despite recent literature suggesting that maternal care is an important environmental factor in the development of behavioral disorders, it is unclear how much maternal care is dysfunctional in BD subjects. Objective: The objective of this study was to characterize maternal care in DSM-IV/SCID diagnosed BD type I subjects compared to healthy controls with (PD) and without (NPD) other psychiatric diagnoses. Materials and methods: Thirty-four BD mothers and 106 controls underwent an interview about family planning and maternal care, obstetrical complications, and mother-child interactions. K-SADS-PL questions about violence exposure were used to ascertain domestic violence and physical/sexual abuse. Results: BD mothers were less likely to have stable unions (45.5%; p < 0.01) or to live with the biological father of their children (33.3%; p < 0.01), but had higher educational level and higher rates of social security use/retirement. They also had fewer children and used less contraceptive methods than controls. Children of BD women had higher rates of neonatal anoxia, and reported more physical abuse (16.1%; p = 0.02) than offspring of NPD mothers. Due to BD mothers' symptoms, 33.3% of offspring suffered physical and/or psychological abuse. Limitations: Post hoc analysis, and the use of questions as a surrogate of symptoms as opposed to validated instruments. Conclusion: This is one of few reports confirming that maternal care given by BD women is dysfunctional. BD psychopathology can lead to poor maternal care and both should be considered important environmental risk factors in BD, suggesting that BD psychoeducation should include maternal care orientation. (C) 2012 Elsevier B.V. All rights reserved.