Miracle-dz/UniFAR-FTUs huggingface dataset:
Lifetime co-morbidities between social phobia and mood disorders in the US National Comorbidity Survey

Background. General population data were used to study co-morbidities between lifetime social phobia and mood disorders. Methods. Data come from the US National Comorbidity Survey (NCS). Results. Strong associations exist between lifetime social phobia and major depressive disorder (odds ratio 2·9), dysthymia (2·7) and bipolar disorder (5·9). Odds ratios increase in magnitude with number of social fears. Reported age of onset is earlier for social phobia than mood disorders in the vast majority of co-morbid cases. Temporally-primary social phobia predicts subsequent onset of mood disorders, with population attributable risk proportions of 10–15%. Social phobia is also associated with severity and persistence of co-morbid mood disorders. Conclusions. Social phobia is a commonly occurring, chronic and seriously impairing disorder that is seldom treated unless it occurs in conjunction with another co-morbid condition. The adverse consequences of social phobia include increased risk of onset, severity and course of subsequent mood disorders. Early outreach and treatment of primary social phobia might not only reduce the prevalence of this disorder itself, but also the subsequent onset of mood disorders.
Nicotine dependence and illness severity in schizophrenia

Background Reasons for the increased prevalence of cigarette smoking in schizophrenia are unclear. Studies assessing clinical symptoms have sampled heterogeneous populations, with discrepant findings. Aims To examine the relationship between clinical features, social adjustment and nicotine dependence in a geographically defined population of people with schizophrenia. Method Cross-sectional clinical study of 131 people with schizophrenia in Nithsdale, Scotland. Results Smokers were younger, mostly males and three times more likely to be unemployed. Those with severe nicotine dependence had greater scores on the positive subscale of the Positive and Negative Syndrome Scale (PANSS), and were prescribed higher doses of antipsychotic. Those with mild–moderate dependence had greater scores on the PANSS negative subscale. Greater symptom severity was associated with poorer social adjustment. Psychopathology and social adjustment were similar in quitters and never-smokers. Conclusions Our findings indicate an association between nicotine dependence, clinical symptoms and social adjustment in schizophrenia. Although causal links cannot be inferred, identifying the relationship between nicotine dependence and psychopathology may have some value in the management of smoking in schizophrenia. Further longitudinal studies are required to explore this relationship.
Female barn owls (Tyto alba) advertise good genes

The good genes hypothesis of sexual selection postulates that ornamentation signals superior genetic quality to potential mates. Support for this hypothesis comes from studies on male ornamentation only, while it remains to be shown that female ornamentation may signal genetic quality as well. Female barn owls (Tyto alba) display more black spots on their plumage than males. The expression of this plumage trait has a genetic basis and it has been suggested that males prefer to mate with females displaying more black spots. Given the role of parasites in the evolution of sexually selected traits and of the immune system in parasite resistance, we hypothesize that the extent of female plumage ‘spottiness’ reflects immunological defence. We assessed the genetic variation in specific antibody production against a non–pathogenic antigen among cross–fostered nestlings and studied its covariation with the plumage spottiness of genetic parents. The magnitude of the antibody response was positively correlated with the plumage spottiness of the genetic mother but not of the genetic father. Our study thereby provides the first experimental support, to our knowledge, for the hypothesis that female ornamentation signals genetic quality.
Independent Effects of Lighting, Orientation, and Stereopsis on the Hollow-Face Illusion

Three experiments were conducted to investigate factors contributing to the ‘hollow face’ illusion. A novel method was employed in which the distance from the mask at which the illusion became apparent or disappeared, when retreating or approaching, respectively, was taken as a measure of the strength of the illusion. In all the experiments an effect of direction of observer's movement was found, demonstrating the stability of the initial percept. Upright orientations were compared with inverted ones to investigate if the illusion reflects a bias towards a familiar percept. The direction of lighting was also varied. Independent main effects of orientation and lighting were found to be consistent with preferences both for upright faces and for top lighting. However, inverted faces also produced the illusion to some extent, suggesting a general preference for convexity. The role of stereopsis in resolving the illusion was tested by comparing monocular with binocular viewing conditions. Monocular viewing conditions gave rise to shorter distances, suggesting that the retinal disparities available with binocular viewing are important in disambiguating the illusion at small distances. The results are interpreted within the framework of a 22-dimensional sketch derived from independent modular processing of visual information.
Spatial localization and time‐dependant changes of electrographic high frequency oscillations in human temporal lobe epilepsy

Purpose: High frequency oscillations (HFOs) >200 Hz are believed to be associated with epileptic processes. The spatial distribution of HFOs and their evolution over time leading up to seizure onset is unknown. Also, recording HFOs through conventional intracranial electrodes is not well established. We therefore wished to determine whether HFOs could be recorded using commercially available depth macroelectrodes. We also examined the spatial distribution and temporal progression of HFOs during the transition to seizure activity.
Rehabilitation following hospitalization in patients with COPD: Can it reduce readmissions?

Exacerbations of chronic obstructive pulmonary disease (COPD) are one of the commonest causes of emergency hospital admission and are associated with high rates of readmission. Rehabilitation in the peri‐ and early post‐hospitalization setting may counteract the deleterious consequences of an acute hospital admission and target modifiable risk factors for readmission such as physical inactivity, reduced exercise capacity and impaired physical function. Pulmonary rehabilitation in the peri‐hospitalization period can improve exercise capacity and health‐related quality of life and can also reduce rates of readmission. Consequently, guidelines have recommended the provision of pulmonary rehabilitation in the acute setting. However, recent trials showing less positive results and observational data questioning acceptability may challenge prevailing enthusiasm. This review examines the role of pulmonary rehabilitation in the peri‐ and early post‐hospitalization setting, considering the modifiable risk factors for readmission, the latest evidence regarding rehabilitation in the acute setting, issues around acceptability and uptake, and alternative strategies to help deliver rehabilitation to more patients. The acceptability and effectiveness of pulmonary rehabilitation offered that post‐exacerbation could be improved by overcoming issues around the setting, timing and format of rehabilitation approaches, including their integration with self‐management interventions.
Molecular cloning of an estrogen receptor beta subtype from the goldfish, Carassius auratus.

The brain of many teleost fish species, including the goldfish Carassius auratus, expresses exceptionally high levels of cytochrome P450 aromatase (estrogen synthetase). To begin investigating the molecular and cellular targets of estrogen action in goldfish brain, a polymerase chain reaction (PCR) cloning strategy was used to isolate an estrogen receptor (ER) complementary DNA (cDNA). The 2283-bp cDNA isolated from goldfish liver encoded a protein of 568 amino acids (aa) with an estimated molecular weight of 63,539. The goldfish ER had high overall sequence identity when compared to other vertebrate ER sequences: eel (64%), human beta subtype (59%), human alpha subtype (46%), medaka (46%), and rainbow trout (47%). The highest degree of conservation was seen in the DNA-binding (94-100%) and ligand-binding (67-79%) domains. Phylogenetic analysis of the ER gene family indicated that the goldfish and eel ER are most closely related to mammalian ERbeta subtypes, whereas previously identified fish, amphibian, and avian ER forms cluster separately with mammalian ERalpha subtypes. Using the goldfish ER cDNA (here designated gfERbeta), multiple mRNA species (3.1- 8.6 kb) were detected by Northern blot analysis in goldfish liver and ovary but expression was below detection in brain. Using reverse transcription-PCR analysis, gfERbeta mRNA was detected in forebrain, mid/hindbrain, pituitary, retina, liver, ovary, and testis. Further studies are required to determine whether an additional ERalpha subtype is present in the goldfish and whether ERalpha or ERbeta forms have evolutionary precedence in vertebrates.
Relationship of Communication and Information Measures to Colorectal Cancer Screening Utilization: Results From HINTS

Utilization of colorectal cancer screening tests is suboptimal. Knowledge of colorectal cancer screening has been associated with completion of screening. Thus, increasing awareness of colorectal cancer screening may lead to significant improvements in screening rates. We assessed for the association among provider–patient interaction, information-seeking patterns, sources of information, trust in cancer information, and Internet usage on colorectal cancer screening behavior using data obtained by the Health Information National Trends Survey (HINTS). From a cohort of 2,670 respondents greater than 50 years of age, we found that they (1) desired cancer information from personalized reading materials, meeting in person with a health care professional, and published materials; and (2) had great trust of information from their provider. Having trust in cancer information from the doctor or other health care professional was most predictive (OR 2.08, 95% CI 1.49–2.94) of being up to date. Other predictive factors include having a desire for cancer information from personalized reading materials (OR 1.56, 95% CI 1.24–1.95) and using the Internet from home (OR 1.32, 95% CI 1.04–1.67). We conclude that personalized communications from a health care provider are desired and trusted. Another promising information delivery approach is the Internet. Dedicated efforts using these approaches for information exchange may be most beneficial toward increasing utilization of colorectal cancer screening.
Identification of a protein secretory pathway for the secretion of heat-labile enterotoxin by an enterotoxigenic strain of Escherichia coli

Enterotoxigenic Escherichia coli (ETEC) is an enteric pathogen that causes cholera-like diarrhea in humans and animals. ETEC secretes a heat-labile enterotoxin (LT), which resembles cholera toxin, but the actual mechanism of LT secretion is presently unknown. We have identified a previously unrecognized type II protein secretion pathway in the prototypic human ETEC strain, H10407 (serotype O78:H11). The genes for this pathway are absent from E. coli K-12, although examination of the K-12 genome suggests that it probably once possessed them. The secretory pathway bears significant homology at the amino acid level to the type II protein secretory pathway required by Vibrio cholerae for the secretion of cholera toxin. With this in mind, we determined whether the homologous pathway of E. coli H10407 played a role in the secretion of LT. To this end, we inactivated the pathway by inserting a kanamycin-resistance gene into one of the genes (gspD) of the type II secretion pathway by homologous recombination. LT secretion by E. coli H10407 and the gspD mutant was assayed by enzyme immunoassay, and its biological activity was assessed by using Y-1 adrenal cells. This investigation showed that the protein secretory pathway is functional and necessary for the secretion of LT by ETEC. Our findings have revealed the mechanism for the secretion of LT by ETEC, which previously was unknown, and provide further evidence of close biological similarities of the LT and cholera toxin.
Analysis of 81 genes from 64 plastid genomes resolves relationships in angiosperms and identifies genome-scale evolutionary patterns

Angiosperms are the largest and most successful clade of land plants with >250,000 species distributed in nearly every terrestrial habitat. Many phylogenetic studies have been based on DNA sequences of one to several genes, but, despite decades of intensive efforts, relationships among early diverging lineages and several of the major clades remain either incompletely resolved or weakly supported. We performed phylogenetic analyses of 81 plastid genes in 64 sequenced genomes, including 13 new genomes, to estimate relationships among the major angiosperm clades, and the resulting trees are used to examine the evolution of gene and intron content. Phylogenetic trees from multiple methods, including model-based approaches, provide strong support for the position of Amborella as the earliest diverging lineage of flowering plants, followed by Nymphaeales and Austrobaileyales. The plastid genome trees also provide strong support for a sister relationship between eudicots and monocots, and this group is sister to a clade that includes Chloranthales and magnoliids. Resolution of relationships among the major clades of angiosperms provides the necessary framework for addressing numerous evolutionary questions regarding the rapid diversification of angiosperms. Gene and intron content are highly conserved among the early diverging angiosperms and basal eudicots, but 62 independent gene and intron losses are limited to the more derived monocot and eudicot clades. Moreover, a lineage-specific correlation was detected between rates of nucleotide substitutions, indels, and genomic rearrangements.
ABO blood group and risk of pancreatic cancer in a Turkish population in Western Blacksea region.

BACKGROUND We aimed to investigate the relationship between blood groups and pancreatic cancer in a Turkish population in Western Blacksea region. METHODS This is a retrospective study. Zonguldak Karaelmas University outpatient oncology clinic records were screened for the period between 2004 and 2011. RESULTS The median age of patients were 56 (± 16) and 132 of 633 study population had pancreatic cancer. Pancreatic cancer patients had significantly higher rates of blood group A compared to controls (OR 1.8, 95%CI, p 0.005). Rates of blood group AB was significantly lower than the control group (OR 0.37, 95% CI, p 0.04). The median survival (IR) time in subjects having the blood groups A, B, AB and O were 7.0 (1-28), 7.0 (2-38), 10 (2-36) and 9.0 (2-48) months respectively; the blood group 0 had significantly higher overall survival (OS) compared to the non-0 groups (p 0.04). CONCLUSIONS Pancreatic cancer patients had more common blood group A in our population. Moreover, blood group AB appeared to be a protective factor against pancreatic cancer in our population. Blood group 0 had a significantly longer survival compared to non-0, regardless of prognostic factors.
Chronic Cigarette Smoke Exposure Primes NK Cell Activation in a Mouse Model of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a debilitating, progressive lung disease punctuated by exacerbations of symptoms. COPD exacerbations are most often associated with viral infections, and exposure to cigarette smoke (CS) followed by viral infection has been shown experimentally to enhance lung inflammation, tissue destruction, and airway fibrosis. Despite this, however, the cellular mechanisms responsible for this effect are unknown. In this study, we examined NK cell function in a mouse model of COPD given the vital role of NK cells following viral infection. Ex vivo stimulation of lung leukocytes with poly(I:C), ssRNA40, or ODN1826 enhanced production of NK cell-derived IFN-γ in CS-exposed mice. NK cells from CS-exposed mice exhibited a novel form of priming; highly purified NK cells from CS-exposed mice, relative to NK cells from filtered air-exposed mice, produced more IFN-γ following stimulation with IL-12, IL-18, or both. Further, NK cell priming was lost following smoking cessation. NKG2D stimulation through overexpression of Raet1 on the lung epithelium primed NK cell responsiveness to poly(I:C), ssRNA40, or ODN1826 stimulation, but not cytokine stimulation. In addition, NK cells from CS-exposed mice expressed more cell surface CD107a upon stimulation, demonstrating that the NK cell degranulation response was also primed. Together, these results reveal a novel mechanism of activation of the innate immune system and highlight NK cells as important cellular targets in controlling COPD exacerbations.
Molecular evolution of breast cancer

Molecular analysis of invasive breast cancer and its precursors has furthered our understanding of breast cancer progression. In the past few years, new multi‐step pathways of breast cancer progression have been delineated through genotypic–phenotypic correlations. Nuclear grade, more than any other pathological feature, is strongly associated with the number and pattern of molecular genetic abnormalities in breast cancer cells. Thus, there are two distinct major pathways to the evolution of low‐ and high‐grade invasive carcinomas: whilst the former consistently show oestrogen receptor (ER) and progesterone receptor (PgR) positivity and 16q loss, the latter are usually ER/PgR‐negative and show Her‐2 overexpression/amplification and complex karyotypes. The boundaries between the evolutionary pathways of well‐differentiated/low‐grade ductal and lobular carcinomas have been blurred, with changes in E‐cadherin expression being one of the few distinguishing features between the two. In addition, lesions long thought to be precursors of breast carcinomas, such as hyperplasia of usual type, are currently considered mere risk indicators, whilst columnar cell lesions are now implicated as non‐obligate precursors of atypical ductal hyperplasia (ADH) and well‐differentiated ductal carcinoma in situ (DCIS). However, only through the combination of comprehensive morphological analysis and cutting‐edge molecular tools can this knowledge be translated into clinical practice and patient management. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Structure and activity of full‐length formin mDia1

Formins are a conserved family of actin assembly‐promoting factors with essential and diverse biological roles. Most of our biochemical understanding of formin effects on actin dynamics is derived from studies using formin fragments. In addition, all structural information on formins has been limited to fragments. This has left open key questions about the structure, activity and regulation of intact formin proteins. Here, we isolated full‐length mouse mDia1 (mDia1‐FL) and found that it forms tightly autoinhibited dimers that can only be partially activated by RhoA. We solved the structure of autoinhibited mDia1‐FL using electron microscopy and single particle analysis. Docking of crystal structures into the three dimensional reconstruction revealed that the fork‐shaped N‐terminal diaphanous inhibitory domain‐coiled coil domain region hangs over the ring‐shaped formin homology (FH)2 domain, suggesting that autoinhibition results from steric obstruction of actin binding. Deletion of the C‐terminal diaphanous autoregulatory domain extended mDia1 structure and activated it for actin assembly. Using total internal reflection fluorescence microscopy, we observed that RhoA‐activated mDia1‐FL persistently accelerated filament elongation in the presence of profilin similar to mDia1 FH1‐FH2 fragment. These observations validate the known activities of FH1‐FH2 fragments as reflecting those of the intact molecule. Our results further suggest that mDia1‐FL does not readily snap back into the autoinhibited conformation and dissociate from growing filament ends, and thus additional factors may be required to displace formins and restrict filament length. © 2012 Wiley Periodicals, Inc
Mitotic Effects of a Constitutively Active Mutant of the Xenopus Polo-Like Kinase Plx1

ABSTRACT During mitosis the Xenopus polo-like kinase 1 (Plx1) plays key roles in the activation of Cdc25C, in spindle assembly, and in cyclin B degradation. Previous work has shown that the activation of Plx1 requires phosphorylation on serine and threonine residues. In the present work, we demonstrate that replacement of Ser-128 or Thr-201 with a negatively charged aspartic acid residue (S128D or T201D) elevates Plx1 activity severalfold and that replacement of both Ser-128 and Thr-201 with Asp residues (S128D/T201D) increases Plx1 activity approximately 40-fold. Microinjection of mRNA encoding S128D/T201D Plx1 into Xenopus oocytes induced directly the activation of both Cdc25C and cyclin B-Cdc2. In egg extracts T201D Plx1 delayed the timing of deactivation of Cdc25C during exit from M phase and accelerated Cdc25C activation during entry into M phase. This supports the concept that Plx1 is a “trigger” kinase for the activation of Cdc25C during the G2/M transition. In addition, during anaphase T201D Plx1 reduced preferentially the degradation of cyclin B2 and delayed the reduction in Cdc2 histone H1 kinase activity. In early embryos S128D/T201D Plx1 resulted in arrest of cleavage and formation of multiple interphase nuclei. Consistent with these results, Plx1 was found to be localized on centrosomes at prophase, on spindles at metaphase, and at the midbody during cytokinesis. These results demonstrate that in Xenopus laevis activation of Plx1 is sufficient for the activation of Cdc25C at the initiation of mitosis and that inactivation of Plx1 is required for complete degradation of cyclin B2 after anaphase and completion of cytokinesis.
Utilization of glutathione S-transferase Mu 1- and Theta 1-null mice as animal models for absorption, distribution, metabolism, excretion and toxicity studies

Introduction: Glutathione S-transferases (GSTs) are Phase II drug-metabolizing enzymes that catalyze the conjugation of electrophilic compounds to glutathione. This reaction generally detoxifies reactive metabolites of xenobiotics, such as drugs and environmental chemicals, and therefore, GSTs are considered toxicologically important enzymes. Human GST genes display genetic polymorphisms, and the impact of null genotypes of GST Mu 1 (GSTM1) and GST Theta 1 (GSTT1) have been extensively studied. Recently, corresponding Gstm1- and Gstt1-null mice have been developed. Areas covered: This review covers GSTM1- and GSTT1-null genotypes in humans and utilization of Gstm1- and Gstt1-null mice as animal models for absorption, distribution, metabolism, excretion and toxicity (ADMET) studies. Furthermore, the possibility of Gstm1- and Gstt1-null mice as models of humans with GSTM1- and GSTT1-null genotypes is discussed. Expert opinion: The experimental approach to assess the impact of GSTM1- and GSTT1- null genotypes on ADMET is very limited so far. Gstm1- and Gstt1-null mice have potential as human models, since null genotypes of GSTM1/Gstm1 and GSTT1/Gstt1 decreased hepatic GST activities toward p-nitrobenzyl chloride and dichloromethane, respectively, in both humans and mice. This suggests functional similarity of GSTM1 and GSTT1 toward some substrates between humans and mice.