Miracle-dz/UniFAR-FTUs huggingface dataset:
BDNF Val66Met Genotype Interacts With a History of Simulated Stress Exposure to Regulate Sensorimotor Gating and Startle Reactivity

Reduced expression of Brain-Derived Neurotrophic Factor (BDNF) has been implicated in the pathophysiology of schizophrenia. The BDNF Val66Met polymorphism, which results in deficient activity-dependent secretion of BDNF, is associated with clinical features of schizophrenia. We investigated the effect of this polymorphism on Prepulse Inhibition (PPI), a translational model of sensorimotor gating which is disrupted in schizophrenia. We utilized humanized BDNFVal66Met (hBDNFVal66Met) mice which have been modified to carry the Val66Met polymorphism, as well as express humanized BDNF in vivo. We also studied the long-term effect of chronic corticosterone (CORT) exposure in these animals as a model of history of stress. PPI was assessed at 30ms and 100ms interstimulus intervals (ISI). Analysis of PPI at the commonly used 100ms ISI identified that, irrespective of CORT treatment, the hBDNFVal/Met genotype was associated with significantly reduced PPI. In contrast, PPI was not different between hBDNFMet/Met and hBDNFVal/Val genotype mice. At the 30ms ISI, CORT treatment selectively disrupted sensorimotor gating of hBDNFVal/Met heterozygote mice but not hBDNFVal/Val or hBDNFMet/Met mice. Analysis of startle reactivity revealed that chronic CORT reduced startle reactivity of hBDNFVal/Val male mice by 51%. However, this was independent of the effect of CORT on PPI. In summary, we provide evidence of a distinct BDNFVal66Met heterozygote-specific phenotype using the sensorimotor gating endophenotype of schizophrenia. These data have important implications for clinical studies where, if possible, the BDNFVal/Met heterozygote genotype should be distinguished from the BDNFMet/Met genotype.
Cloning, expression and purification of extracellular serine protease Esp, a biofilm‐degrading enzyme, from Staphylococcus epidermidis

Aims: Staphylococcus epidermidis Esp, an extracellular serine protease, inhibits Staphylococcus aureus biofilm formation and nasal colonization. To further expand the biotechnological applications of Esp, we developed a highly efficient and economic method for the purification of recombinant Esp based on a Brevibacillus choshinensis expression–secretion system.
Further evidence for shared genetic effects between psychotic bipolar disorder and P50 suppression: A combined twin and family study

P50 suppression deficit has been reported in patients with psychotic bipolar disorder. In our previous report on twin pairs concordant and discordant for bipolar disorder, we found significant genetic overlap between bipolar disorder and P50 sensory gating. However, the sample size in that study was relatively small. A separate study, the Maudsley Bipolar Family Study, reported diminished P50 gating in unaffected relatives of psychotic bipolar patients. However, genetic and environmental influences are confounded in family studies due to lack of monozygotic (MZ) twin pairs. The current study combines the twin sample and the family sample in order to improve statistical power and study design, with the aims of: (1) substantiating the association between psychotic bipolar disorder and diminished P50 suppression and (2) verifying the genetic overlap between the two traits reported in the twin sample. We also assessed the relationship between bipolar disorder and an alternative suppression index, the P50 Condition–Testing (C–T) amplitude difference. A total of 309 subjects was included in this study, comprising 91 twin pairs, 31 bipolar families, and 45 unrelated healthy controls. Statistical analyses were based on structural equation modeling. Bipolar disorder was significantly associated with a diminished P50 suppression ratio and decreased C–T amplitude difference. Shared genetic factors were the main source of these associations. Suppression impairment was due to larger, poorly gated, T amplitude responses. The results provide further evidence that impaired P50 suppressions are promising endophenotypes for psychotic bipolar disorder. The non‐specificity of impaired P50 suppression may reflect the impact of shared psychosis susceptibility genes. © 2008 Wiley‐Liss, Inc.
Pseudomonas putida NBRIC19 dihydrolipoamide succinyltransferase (SucB) gene controls degradation of toxic allelochemicals produced by Parthenium hysterophorus

Aims: The aim of this study was to identify the gene responsible for degradation of toxic allelochemicals of Parthenium by generating Tn5‐induced mutant of Pseudomonas putida NBRIC19. Furthermore, the study characterizes the mutant at physiological, biochemical and molecular level that helped in understanding the mechanisms of reducing the allelopathic inhibition of Parthenium by Ps. putida NBRIC19.
Altered Coupling Between Resting-State Cerebral Blood Flow and Functional Connectivity in Schizophrenia

Background Respective changes in resting-state cerebral blood flow (CBF) and functional connectivity in schizophrenia have been reported. However, their coupling alterations in schizophrenia remain largely unknown. Methods 89 schizophrenia patients and 90 sex- and age-matched healthy controls underwent resting-state functional MRI to calculate functional connectivity strength (FCS) and arterial spin labeling imaging to compute CBF. The CBF-FCS coupling of the whole gray matter and the CBF/FCS ratio (the amount of blood supply per unit of connectivity strength) of each voxel were compared between the 2 groups. Results Whole gray matter CBF-FCS coupling was decreased in schizophrenia patients relative to healthy controls. In schizophrenia patients, the decreased CBF/FCS ratio was predominantly located in cognitive- and emotional-related brain regions, including the dorsolateral prefrontal cortex, insula, hippocampus and thalamus, whereas an increased CBF/FCS ratio was mainly identified in the sensorimotor regions, including the putamen, and sensorimotor, mid-cingulate and visual cortices. Conclusion These findings suggest that the neurovascular decoupling in the brain may be a possible neuropathological mechanism of schizophrenia.
Polymorphisms in the 3′ UTR of the serotonin transporter are associated with cognitive flexibility in rhesus macaques

The serotonin system is an important neurophysiological mediator of many behavioral phenotypes. Genetic variation within this system is thought to contribute not only to the natural range of behavioral differences, but also to neuropsychiatric pathologies. Cognitive flexibility, the ability to change patterns of response as reward context shifts, is an important trait that underlies many complex social interactions. Environmental manipulations of the serotonin system have been shown to alter performance on tests measuring cognitive flexibility. Variation at the serotonin transporter promoter region (5HTTLPR) has recently been shown to associate with the performance of rhesus monkeys on an object discrimination reversal learning task [Izquierdo et al., 2007 ]. Here, we demonstrate that functional genetic variation at the serotonin transporter 3′ untranslated region, independent of 5HTTLPR, also associates with performance in an object discrimination reversal learning task in rhesus macaques. The polymorphisms comprising the T:G:T haplotype (T1970, G1991, and T2327) were associated with fewer errors on a reversal learning test and greater levels of cognitive flexibility. We have previously demonstrated that the T:G:T haplotype renders lower levels of gene expression in vitro, paralleling the functionality of human 3′ UTR haplotypes, as well as the short allele of 5HTTLPR found in both macaques and humans. The 3′ UTR haplotypes are independent and in linkage equilibrium with the 5HTTLPR locus. Together, these data lead to the intriguing possibility that differences observed in human cognitive flexibility, whether naturally or in pathological states, may be associated with genetic variation in the serotonin transporter 3′ untranslated region also. © 2008 Wiley‐Liss, Inc.
AGENESIA PARCIAL DO SACO PERICÁRDIO EM CÃO – RELATO DE CASO

The pericardium is a membranous sack that involves the heart, and partly the great vases, that presents mechanics and membranous functions. Congenital defects of the pericardium are extremely rare, most being discovered accidentally in the post-mortem exam. The objective of this work was to relate the anatomic-pathological discoveries of a dog with partial agenesis of the pericardium sack. It was necropsied, in the Laboratory of Veterinary Pathology of the UFERSA, Mossoro-RN, a male dog, without defined race, with 10 years of age, with the clinical report of Visceral Leishmaniasis. In the thoracic cavity it was verified the partial absence of the pericardium sack with exhibition of part of the atrium and right auricle that presented hypertrophied. The presence of a demarcation line was verified on the hernia place of the heart. In the internal exam of the heart it was observed that the right atrium presented eccentric hypertrophy while the left atrium, right and left ventricle presented concentric hypertrophy.
A Mixed Method Study on the Peripartum Experience and Postpartum Effects of Emergency Hysterectomy Due To Postpartum Hemorrhage

Background: Little is known about the experience and psychological outcomes for women who experience emergency peripartum hysterectomy (EPH). The objective of this study was to explore women’s experiences of EPH and to determine if women who experience EPH were more likely to experience mental health sequelae. Methods: This mixed method design involved a quantitative and a qualitative phase. The quantitative phase used a retrospective cohort design. Women were sampled through on-line communities, including an EPH support group, and a larger website for mothers. Women completed on-line surveys covering sociodemographic, obstetric/gynecological and psychiatric information, including screens for depression and Post-Traumatic Stress Disorder (PTSD). Logistic regression was used to calculate the independent risk that exposure to EPH has on screening positive for PTSD. Participants from the EPH support group who completed the on-line interview were then selected to participate in the second phase. In-depth telephone interviews were conducted and analyzed using Constant Comparative Analysis. Results: 74 exposed women and 355 non-exposed women completed the survey. In the adjusted logistic regression model, women who experienced EPH were over 6 times more likely to screen positive for current PTSD compared to women who did not experience EPH (adjusted Relative Risk (aRR): 6.76; 95% CI: 4.24, 8.88). When women recalled their psychological state at 6 months postpartum, exposed women were 11 times more vii likely to screen positive for current PTSD (aRR: 11.35; 95% CI: 8.43, 12.95). In the qualitative phase, 15 women participated and 7 major themes were identified: fear, pain, death and dying, numbness or delay in emotional reaction, bonding with baby, communication and the need for information. A major finding is the need for additional follow-up visits to address the emotional after-effects and to fill in gaps in women’s understanding and memory of what had occurred. Conclusion: Understanding women’s experiences and sequelae can help providers address not only women’s initial complications but provide needed long-term support.
A family‐based association study of the glutamate transporter gene SLC1A1 in obsessive–compulsive disorder in 378 families

SLC1A encodes the neuronal and epithelial glutamate transporter and was previously tested as a candidate for obsessive–compulsive disorder (OCD) by several research groups. Recently, three independent research groups reported significant association findings between OCD and several genetic variants in SLC1A1. This study reports the results from a family‐based association study, which examined the association between 13 single nucleotide polymorphisms (SNPs) within or in proximity to the SLC1A1 gene. Although we did not replicate association findings for those significant SNPs reported by previous studies, our study indicated a strong association signal with the SNP RS301443 (P‐value = 0.000067; Bonferroni corrected P‐value = 0.0167) under a dominant model, with an estimated odds ratio of 3.5 (confidence interval: 2.66–4.50). Further, we conducted single SNP analysis after stratifying the full data set by the gender status of affecteds in each family. The P‐value for RS301443 in families with the male affecteds was 0.00027, and the P‐value in families with female affecteds was 0.076. The fact that we identified a signal which was not previously reported by the other research groups may be due to differences in study designs and sample ascertainment. However, it is also possible that this significant SNP may be part of a regulator for SLC1A1, given that it is roughly 7.5 kb away from the boundary of the SLC1A1 gene. However, this potential finding needs to be validated biologically. Further functional studies in this region are planned by this research group. © 2009 Wiley‐Liss, Inc.
Transparency in information about health - improving medical decision making

17 Introduction . 18 Comparison of the three major approaches . 18 When to apply which strategy? 21 Conclusions . 23 References . 25 Do the media provide transparent health information? A cross-cultural comparison of public information about the HPV vaccine . 28 Abstract . 29 Introduction . 30 Method . 34 Results . 36 Discussion . 41 References . 46 Appendix A . 53 Appendix B . 55 Appendix C . 56 Improving the understanding of relative risk information with baseline risk: The role of presentation format and numeracy . 59.29 Introduction . 30 Method . 34 Results . 36 Discussion . 41 References . 46 Appendix A . 53 Appendix B . 55 Appendix C . 56 Improving the understanding of relative risk information with baseline risk: The role of presentation format and numeracy . 59 Abstract . 60 Introduction . 61 Experiment 1a . 68 Method . 68 Results and Discussion . 69 Experiment 1b . 73 Method . 73 Results and Discussion . 73 Experiment 2a . 76 Method . 78.60 Introduction . 61 Experiment 1a . 68 Method . 68 Results and Discussion . 69 Experiment 1b . 73 Method . 73 Results and Discussion . 73 Experiment 2a . 76 Method . 78
Fast Association and Slow Transitions in the Interaction between Two Intrinsically Disordered Protein Domains*

Background: Intrinsically disordered proteins are common regulators of protein-protein interactions, but little is known about their mechanisms of interaction. Results: Two intrinsically disordered protein domains, from ACTR and CREB-binding protein, interact through rapid association and slow conformational changes. Conclusion: Electrostatics governs the fast association, but the overall reaction is multistep. Significance: The slow conformational search may be common among intrinsically disordered proteins with many binding partners. Proteins that contain long disordered regions are prevalent in the proteome and frequently associated with diseases. However, the mechanisms by which such intrinsically disordered proteins (IDPs) recognize their targets are not well understood. Here, we report the first experimental investigation of the interaction kinetics of the nuclear co-activator binding domain of CREB-binding protein and the activation domain from the p160 transcriptional co-activator for thyroid hormone and retinoid receptors. Both protein domains are intrinsically disordered in the free state and synergistically fold upon binding each other. Using the stopped-flow technique, we found that the binding reaction is fast, with an association rate constant of 3 × 107 m−1 s−1 at 277 K. Mutation of a conserved buried intermolecular salt bridge showed that electrostatics govern the rapid association. Furthermore, upon mutation of the salt bridge or at high salt concentration, an additional kinetic phase was detected (∼20 and ∼40 s−1, respectively, at 277 K), suggesting that the salt bridge may steer formation of the productive bimolecular complex in an intramolecular step. Finally, we directly measured slow kinetics for the IDP domains (∼1 s−1 at 277 K) related to conformational transitions upon binding. Together, the experiments demonstrate that the interaction involves several steps and accumulation of intermediate states. Our data are consistent with an induced fit mechanism, in agreement with previous simulations. We propose that the slow transitions may be a consequence of the multipartner interactions of IDPs.
A broad spectrum of developmental delay in a large cohort of prolidase deficiency patients demonstrates marked interfamilial and intrafamilial phenotypic variability

Prolidase deficiency (PD) is a rare, pan‐ethnic, autosomal recessive disease with a broad phenotypic spectrum. Seventeen causative mutations in the PEPD gene have been reported worldwide. The purpose of this study is to characterize, clinically and molecularly, 20 prolidase deficient patients of Arab Moslem and Druze origin from 10 kindreds residing in northern Israel. All PD patients manifested developmental delay and facial dysmorphism. Typical PD dermatological symptoms, splenomegaly, and recurrent respiratory infections presented in varying degrees. Two patients had systemic lupus erythematosus (SLE), and one a novel cystic fibrosis phenotype. Direct DNA sequencing revealed two novel missense mutations, A212P and L368R. In addition, a previously reported S202F mutation was detected in 17 patients from seven Druze and three Arab Moslem kindreds. Patients homozygous for the S202F mutation manifest considerable interfamilial and intrafamilial phenotypic variability. The high prevalence of this mutation among Arab Moslems and Druze residing in northern Israel, and the presence of an identical haplotype along 500,000 bp in patients and their parents, suggests a founder event tracing back to before the breakaway of the Druze from mainstream Moslem society. © 2009 Wiley‐Liss, Inc.
Extracellular Signal-regulated Kinase 5 (ERK5) Mediates Prolactin-stimulated Adult Neurogenesis in the Subventricular Zone and Olfactory Bulb*

Background: Signaling mechanisms underlying prolactin-induced adult neurogenesis are unknown. Results: Prolactin activates ERK5 in SVZ; suppression of ERK5 expression in vitro and erk5 deletion in vivo attenuates prolactin-induced adult neurogenesis. Conclusion: ERK5 is an important mediator in prolactin-stimulated adult neurogenesis. Significance: Elucidation of signaling pathways underlying prolactin-induced adult neurogenesis is critical for understanding the fundamental role of adult neurogenesis in reproductive functions and behaviors. Prolactin-stimulated adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) mediates several reproductive behaviors including mating/pregnancy, dominant male pheromone preference in females, and paternal recognition of offspring. However, downstream signaling mechanisms underlying prolactin-induced adult neurogenesis are completely unknown. We report here for the first time that prolactin activates extracellular signal-regulated kinase 5 (ERK5), a MAP kinase that is specifically expressed in the neurogenic regions of the adult mouse brain. Knockdown of ERK5 by retroviral infection of shRNA attenuates prolactin-stimulated neurogenesis in SVZ-derived adult neural stem/progenitor cells (aNPCs). Inducible erk5 deletion in adult neural stem cells of transgenic mice inhibits neurogenesis in the SVZ and OB following prolactin infusion or mating/pregnancy. These results identify ERK5 as a novel and critical signaling mechanism underlying prolactin-induced adult neurogenesis.
Unstable familial transmissions of Huntington disease alleles with 27–35 CAG repeats (intermediate alleles)

There are inconsistent reports regarding the likelihood of repeat instability for alleles with 27–35 CAG repeats in the Huntington disease (HD) gene. We have examined the intergenerational stability of such intermediate alleles in 51 families from the University of British Columbia's DNA and Tissue Bank for Huntington Disease Research (UBC‐HD Databank). A total of 181 transmissions were identified, with 30% (n = 54/181) of the alleles being unstable upon transmission. The unstable transmissions included both expansions (n = 37) and contractions (n = 17) of CAG size. Of the expanded alleles, 68% (n = 25/37) expanded into the HD range (>36 CAG). Therefore, 14% (n = 25/181) of the 27–35 CAG allele transmissions examined expanded into the disease‐associated range resulting in a new mutation for HD. Significantly, of these new mutations, 40% (n = 10/25) originated from an allele with 35 CAG repeats with CAG repeat expansions ranging from +1 CAG to +23 CAG. The proportion of new mutations in the UBC‐HD Databank is consistent with the most recent new mutation rate for HD, estimated to be at least 10%. The observed difference in the stability of HD intermediate allele transmissions in this data set and in other studies may be a reflection of a small sample size. Alternately, these inconsistencies may indicate an underlying difference in genetic factors which influence repeat instability between the different populations examined. Additional studies determining the frequency and magnitude of repeat instability in this CAG repeat range and factors that influence instability are urgently needed. Until we understand the clinical implications of HD alleles with 27–35 CAG repeats and establish reliable risks of instability, we should exercise caution when translating these results to the clinic. © 2009 Wiley‐Liss, Inc.
A comparison between EASI system 12-lead ECGs and standard 12-lead ECGs for improved clinical nursing practice.

AIMS AND OBJECTIVES This study was carried out to verify the accuracy of 12-Lead ECG, obtained through a continuous ECG monitoring system with five cables positioned in EASI mode, to identify basic ECG alterations. BACKGROUND This study concerns continuous ECG monitoring systems in Coronary Care Units. Continuous ECG monitoring is an important device for nursing surveillance and is useful in decreasing adverse events. DESIGN AND METHOD Thirteen patients admitted consecutively to the Coronary Care Unit for Acute Myocardial Infarction underwent daily and simultaneous recording of a12-lead ECG using both procedures: EASI ECG and STANDARD ECG. A sample of 1,164 ECG leads acquired in EASI mode was compared with a sample of as many ECG leads acquired using the standard procedure with a traditional cardiograph. RESULTS AND CONCLUSIONS In the Coronary Care Unit, Continous ECG monitoring with five cables positioned in EASI mode is a valid alternative to the standard 12-lead ECG for cardiac rhythm abnormalities detection and for acute myocardial ischemia and old myocardial infarction assessment. Therefore, the EASI system might be advantageous for long-term patient monitoring. RELEVANCE TO CLINICAL PRACTICE The EASI system represents a valid device for the nursing surveillance of patients who need continuous ECG monitoring, improves clinical nursing practice in Coronary Care Units, supports the reduction of adverse events such as cardiac arrest and reduces the hospital costs.