Miracle-dz/UniFAR-FTUs huggingface dataset:
Autoantibodies in Human Diabetic Depression Inhibit Adult Neural Progenitor Cells In vitro and Induce Depressive-Like Behavior in Rodents.

Aim Diabetic depression increases in association with microvascular complications. We tested a hypothesis that circulating autoantibodies having anti-endothelial and anti-neuronal properties increase in subsets of diabetes with co-morbid depression. Methods Protein-A eluates from plasma of 20 diabetic depression patients and 30 age-matched controls were tested for effects on endothelial cell survival, neurite outgrowth in rat pheochromocytoma (PC12) cells, or process extension and survival in adult rat dentate gyrus neural progenitor cells. The protein-A eluates from depressed or non-depressed, diabetic patients were injected (via intracerebroventricular route) into mice and 7-10 days later behavioral tests (sucrose preference, and tail suspension tests) were conducted to determine whether the autoantibodies induced anhedonia or despair. Results Diabetic depression (n=20) autoantibodies caused a significant inhibition of PC12 cell neurite outgrowth (P<0.001) or endothelial cell proliferation compared to autoantibodies in control, diabetic (n=20) or non-diabetic (n=10) patients without depression. Process extension and survival in adult rat dentate gyrus neural progenitor cells was significantly reduced (P<0.001) by diabetic depression autoantibodies (n= 11) compared to the effects from similar concentrations (5-7 μg/mL) of autoantibodies in diabetic (n=12) or non-diabetic patients without depression (n=7). Ten micromolar concentrations of Y27632, a selective Rho-Associated Protein Kinase (ROCK) inhibitor, significantly prevented (P<0.0001) neural progenitor cell process retraction induced by diabetes depression autoantibodies (n=5). Mice treated with diabetic depression autoantibodies (n=16 from two different patients' autoantibodies) exhibited significantly reduced (P=0.027) sucrose preference (anhedonia) compared to mice treated with diabetic control autoantibodies (n=16 from two different patients' autoantibodies). Conclusion These data suggest that autoantibodies in a subset of older adult diabetic depression inhibit endothelial cell survival, and impair process extension and survival in adult dentate gyrus neural progenitor cells in vitro.
The Possibility to Use Simple Validated Questionnaires to Predict Long-Term Health Problems After Whiplash Injury

Study Design. A prospective follow-up study. Objectives. To evaluate the relation of the state of health before the accident and the significance of the symptoms reported soon after the injury to the situation 3 years after the injury. To evaluate the possibility of using simple validated questionnaires to predict long-term health problems after the injury. Summary of Background Data. A whiplash injury is generally benign in its natural course. However, some of the patients have diverse and prolonged symptoms. Although several prognostic factors have been suggested for the poor recovery, in most cases the factors leading to prolonged disability remain unclear. Methods. In collaboration with traffic insurance companies, we gathered information of neck injuries that occurred in traffic accidents in Finland in 1998. After the insurance company received a notification of a neck injury and consent from the injured party to participate in the study, they sent the information to the research team. The first inquiry was sent to the patients as soon as possible. One- and three-year follow-up questionnaires were posted to those who responded to the first inquiry. A total of 144 persons returned the 3-year follow-up questionnaires and form the material of this study. Results. A poor state of health or frequent neck pain or headache before the accident did not have any significant relation to the poor outcome 3 years after the accident. The extent of neck pain and lower back pain reported soon after the accident was significantly associated to a poor outcome in the follow-up. The Neck Disability Index questionnaire was significantly related to the poor outcome after 3 years. Conclusions. The subjective experience of a notably decreased level of activity because of the neck pain when supplemented by the enhanced score of Neck Disability Index questionnaire predicts well poor outcome in long-term follow-up and can be used as a tool to identify persons who are at risk to suffer long-term health problems after whiplash injury.
The Human SPT20-Containing SAGA Complex Plays a Direct Role in the Regulation of Endoplasmic Reticulum Stress-Induced Genes

ABSTRACT One of the central questions in eukaryotic transcription is how activators can transmit their signal to stimulate gene expression in the context of chromatin. The multisubunit SAGA coactivator complex has both histone acetyltransferase and deubiquitination activities and remodels chromatin to allow transcription. Whether and how SAGA is able to regulate transcription at specific loci is poorly understood. Using mass spectrometry, immunoprecipitation, and Western blot analysis, we have identified human SPT20 (hSPT20) as the human homologue of the yeast Spt20 and show that hSPT20 is a bona fide subunit of the human SAGA (hSAGA; previously called TFTC/STAGA/PCAF) complex and that hSPT20 is required for the integrity of the hSAGA complex. We demonstrate that hSPT20 and other hSAGA subunits, together with RNA polymerase II, are specifically recruited to genes induced by endoplasmic reticulum (ER) stress. In good agreement with the recruitment of hSAGA to the ER stress-regulated genes, knockdown of hSTP20 hampers ER stress response. Surprisingly, hSPT20 recruitment was not observed for genes induced by another type of stress. These results provide evidence for a direct and specific role of the hSPT20-containing SAGA complex in transcriptional induction of ER stress-responsive genes. Thus, hSAGA regulates the transcription of stress-responsive genes in a stress type-dependent manner.
Revision cochlear implantation for facial nerve stimulation in otosclerosis.

OBJECTIVE To find if patients experiencing postsurgical facial nerve stimulation caused by underlying disease process (ie, otosclerosis) can improve their hearing performance with their cochlear implant by reimplantation and by an optimal programming strategy. DESIGN Retrospective analysis. SETTING Academic tertiary referral center. PATIENTS Two cochlear otosclerosis patients with resistant facial nerve stimulation (FNS). Both patients were initially implanted with Nucleus 22 devices (Cochlear Corporation, Englewood, Colo) and they developed FNS after a period of use. Owing to the decreasing number of active electrodes, concurrent decreases in speech understanding occurred. INTERVENTIONS Various programming approaches were used to address the FNS. Both subjects ultimately received Nucleus 24 devices. One was reimplanted in the same ear, and the other was implanted in the opposite ear. Both have been followed up for 8 months following the reimplantation. MAIN OUTCOME MEASURES Cochlear implant programming levels, cochlear implant performance, and facial nerve stimulation. RESULTS The FNS was managed for more than 3 years through optimized programming. However, the FNS progressed until performance dropped below acceptable levels. Reimplantation was believed to be the only option for improvement. After reimplantation and programming, both subjects showed immediate improvement in speech discrimination. One user increased his consonant-nucleus-consonant word score from 12% preoperatively to 42%, and the other's performance increased from 0% to 86%. CONCLUSIONS Our results suggest that having more programming options with newer devices is critical in otosclerotic or ossified users who experience FNS. Also, reimplantation may be a useful tool to improve performance.
Abscisic Acid Synthesis and Response

ABSTRACT Abscisic acid (ABA) is one of the “classical” plant hormones, i.e. discovered at least 50 years ago, that regulates many aspects of plant growth and development. This chapter reviews our current understanding of ABA synthesis, metabolism, transport, and signal transduction, emphasizing knowledge gained from studies of Arabidopsis. A combination of genetic, molecular and biochemical studies has identified nearly all of the enzymes involved in ABA metabolism, almost 200 loci regulating ABA response, and thousands of genes regulated by ABA in various contexts. Some of these regulators are implicated in cross-talk with other developmental, environmental or hormonal signals. Specific details of the ABA signaling mechanisms vary among tissues or developmental stages; these are discussed in the context of ABA effects on seed maturation, germination, seedling growth, vegetative stress responses, stomatal regulation, pathogen response, flowering, and senescence.
Prognostic Factors in Treatment of Depressive States with Imipramine

Accurate diagnosis within the group of depressive states is generally agreed to be difficult. Some deny the difficulty by ignoring its existence, assuming that these cases form a homogeneous continuum. But even those who share this belief-Garmany (1958) for instanceadmit discrepant results from treatment and, moreover, that there are differences in symptomatology between those -who respond, say, to E.C. T. , and those who do not. Imipramine, as many clinical trials-all but a handful, alas, uncontrolled-have shown, is an effective agent in the treatment of depressive illness. However, substantial numbers of patients fail to show any sustained response to the drug. When a double-blind controlled study of the effects of imipramine upon depressive states was undertaken it
Biochemical and Genetic Evidence formeta-Ring Cleavage of 2,4,5-Trihydroxytoluene inBurkholderia sp. Strain DNT

ABSTRACT 2,4,5-Trihydroxytoluene (THT) oxygenase fromBurkholderia sp. strain DNT catalyzes the conversion of THT to an unstable ring fission product. Biochemical and genetic studies of THT oxygenase were undertaken to elucidate the mechanism of the ring fission reaction. The THT oxygenase gene (dntD) was previously localized to the 1.2-kb DNA insert subcloned in the recombinant plasmid designated pJS76 (W. C. Suen and J. C. Spain, J. Bacteriol. 175:1831–1837, 1993). Analysis of the deduced amino acid sequence of DntD revealed the presence of the highly conserved residues characteristic of the catechol 2,3-dioxygenase gene family I. The deduced amino acid sequence of DntD corresponded to a molecular mass of 35 kDa. The native molecular masses for the THT oxygenase estimated by using gel filtration chromatography and nondenaturing gel electrophoresis were 67.4 and 77.8 kDa, respectively. The results suggested that the native protein consists of two identical subunits. The colorless protein contained 2 mol of iron per mol of protein. Stimulation of activity in the presence of ferrous iron and ascorbate suggested a requirement for ferrous iron in the active site. The properties of the enzyme are similar to those of the catechol 2,3-dioxygenases (meta-cleavage dioxygenases). In addition to THT, the enzyme exhibited activity towards 1,2,4-benzenetriol, catechol, 3- and 4-methylcatechol, and 3- and 4-chlorocatechol. The chemical analysis of the THT ring cleavage product showed that the product was 2,4-dihydroxy-5-methyl-6-oxo-2,4-hexadienoic acid, consistent with extradiol ring fission of THT.
Microbiome Analysis of Stool Samples from African Americans with Colon Polyps

Background Colonic polyps are common tumors occurring in ~50% of Western populations with ~10% risk of malignant progression. Dietary agents have been considered the primary environmental exposure to promote colorectal cancer (CRC) development. However, the colonic mucosa is permanently in contact with the microbiota and its metabolic products including toxins that also have the potential to trigger oncogenic transformation. Aim To analyze fecal DNA for microbiota composition and functional potential in African Americans with pre-neoplastic lesions. Materials & Methods We analyzed the bacterial composition of stool samples from 6 healthy individuals and 6 patients with colon polyps using 16S ribosomal RNA-based phylogenetic microarray; the Human intestinal Tract Chip (HITChip) and 16S rRNA gene barcoded 454 pyrosequencing. The functional potential was determined by sequence-based metagenomics using 454 pyrosequencing. Results Fecal microbiota profiling of samples from the healthy and polyp patients using both a phylogenetic microarraying (HITChip) and barcoded 454 pyrosequencing generated similar results. A distinction between both sets of samples was only obtained when the analysis was performed at the sub-genus level. Most of the species leading to the dissociation were from the Bacteroides group. The metagenomic analysis did not reveal major differences in bacterial gene prevalence/abundances between the two groups even when the analysis and comparisons were restricted to available Bacteroides genomes. Conclusion This study reveals that at the pre-neoplastic stages, there is a trend showing microbiota changes between healthy and colon polyp patients at the sub-genus level. These differences were not reflected at the genome/functions levels. Bacteria and associated functions within the Bacteroides group need to be further analyzed and dissected to pinpoint potential actors in the early colon oncogenic transformation in a large sample size.
Internetwork magnetic field distribution from simultaneous 1.56 $\mathsf{\mu}$m and 630 nm observations

Aims. We study the contradictory magnetic field strength distributions retrieved from independent analyses of spectropolarimetric observations in the near-infrared (1.56 µm) and in the visible (630 nm) spectral ranges in internetwork regions. Methods. To solve this apparent controversy, we present simultaneous and co-spatial 1.56 µm and 630 nm observations of an internetwork area. The properties of the circular and linear polarization signals, as well as the Stokes V area and amplitude asymmetries, are discussed. As a complement, we also used inversion techniques to infer the physical parameters of the solar atmosphere. As a first step, the infrared and visible observations are analysed separately to check their compatibility. Finally, the simultaneous inversion of the two data sets is performed. Results. The magnetic flux densities retrieved from the individual analysis of the infrared and visible data sets are strongly correlated. The polarity of the Stokes V profiles is the same at co-spatial pixels in both wavelength ranges. This indicates that both 1.56 µm and 630 nm observations trace the same magnetic structures on the solar surface. The simultaneous inversion of the two pairs of lines reveals an internetwork full of sub-kG structures that fill only 2% of the resolution element. A correlation is found between the magnetic field strength and the continuum intensity: equipartition fields (B ∼ 500 G) tend to be located in dark intergranular lanes, whereas weaker field structures are found inside granules. The most probable unsigned magnetic flux density is 10 Mx/cm 2 . T he net magnetic flux density in the whole field of view is nearly zero. This means that both polarities cancel out almost exactly in our observed internetwork area.
Adaptive feature selection for kinship verification

Kinship verification from facial images is a challenging task in computer vision. The majority of recent verification algorithms concatenate all features of patches in facial image to build the final feature representation, which implicitly takes every facial part into account for kinship verification. However, it is questionable by considering all face regions since certain facial parts such as the eyes of a child look like the other parent or someone else, which could decrease the verification performance of an algorithm. Motivated by this observation, we attempt to automatically single out the discriminative patches of face and discard interferential ones. Specifically, each weak classifier of AdaBoost is adaptively trained to select a feature composed of some crucial feature patches and various features can be obtained by different weak classifiers. In the stage of verification, a strong classifier constructed by these weak classifiers ensembling is utilized to merge the contributions of selected distinct face areas. Experimental results on KinfaceW-I and KinfaceW-II datasets demonstrate the efficacy of the proposed method compared with state-of-the-art kinship verification approaches.
The Impact of Isoniazid Resistance on the Treatment Outcomes of Smear Positive Re-Treatment Tuberculosis Patients in the State of Andhra Pradesh, India

Background Multi drug resistant and rifampicin resistant TB patients in India are treated with the World Health Organization (WHO) recommended standardized treatment regimens but no guidelines are available for the management of isoniazid (INH) resistant TB patients. There have been concerns that the standard eight-month retreatment regimen being used in India (2H3R3Z3E3S3/1H3R3Z3E3/5H3R3E3; H-Isoniazid; R-Rifampicin; Z-Pyrazinamide; E-Ethambutol; S-Streptomycin) may be inadequate to treat INH resistant TB cases and leads to poor treatment outcomes. We aimed to assess if INH resistance is associated with unfavorable treatment outcomes (death, default, failure and transferred out) among a cohort of smear positive retreatment TB patients registered in three districts of Andhra Pradesh, India. Methods We conducted a retrospective record review of all smear positive retreatment TB patients without rifampicin resistance registered during April–December 2011. Results Of 1,947 TB patients, 1,127 (58%) were tested with LPA—50 (4%) were rifampicin resistant, 933 (84%) were sensitive to INH and rifampicin and 144 (12%) were INH resistant. Of 144 INH resistant cases, 64 (44%) had poor treatment outcomes (25 (17%) default, 22 (15%) death, 12 (8%) failure and 5 (3%) transfer out) as compared to 287 (31%) among INH sensitive cases [aRR 1.46; 95%CI (1.19–1.78)]. Conclusion Our study confirms that INH resistance is independently associated with unfavorable treatment outcomes among smear positive retreatment TB patients, indicating that the current treatment regimen may be inadequate. These findings call for an urgent need for randomized controlled trials to discover the most effective treatment regimen for managing INH resistant TB.
Foreign Customer Accumulation and Export Dynamics

I present a dynamic fixed cost model of export participation extended by a capital theoretic concept of the customer stock. Plants that want to start exporting have to invest into a market specific factor which serves as input into a decreasing returns to scale technology generating sales demand. Customer capital, like phyical capital, depreciates over time and its accumulation is subject to adjustment costs. It allows the model to reproduce the empirical fact that new exporters show above average revenue growth rates and a declining exit hazard in the years after entry. I structurally estimate the model on a rich panel data set of German manufacturing plants between 1995 and 2008. During the observed time span, plants in the sample saw a strong increase in export activity which provides a suitable case study for the predictive power of the model. Unlike a pure fixed cost version, the model correctly forecasts a steep rise in exports after 2003. It is also able to reconcile a strong export reaction to trade liberalizations with a low elasticity of aggregate exports to exchange rate movements. Customer capital accumulation therefore offers a potential resolution to the elasticity puzzle in international economics.
National Guidelines for the prevention of mother-to-child transmission of HIV across Europe - how do countries differ?

OBJECTIVES The aim was to summarize national prevention of mother-to-child transmission (PMTCT) guidelines across Europe and to identify differences between these. METHODS A survey was conducted using a structured questionnaire sent to experts in 25 European countries from January to March 2012, requesting a copy of the national guidelines. Responses were received from 23 countries. RESULTS Twenty-two (96%) countries supported a policy to recommend antenatal HIV screening for all pregnant women (15: opt-out strategy; 8: opt-in strategy). For HIV-positive women in whom the only indication for antiretroviral therapy (ART) was PMTCT, the recommended gestational age for commencing ART varied from 12 to 28 weeks: initiation before 19 weeks gestation was recommended in guidelines from nine countries; in France, the UK and the Netherlands, there was a wide range, from 14 to 24 weeks, whereas the Swiss and Ukrainian guidelines recommended starting at 24-28 weeks and the German/Austrian and Lithuanian at 28 weeks. Six national guidelines recommended inclusion of Zidovudine in antenatal ART regimens, and seven (37%) allowed continuation of Efavirenz for women conceiving on this drug. According to nine guidelines, zidovudine should always be used intrapartum. Eighteen national guidelines stated that HIV-positive women on successful ART can have a vaginal delivery. Viral load thresholds for vaginal delivery were <1000 copies/ml in 5 countries, <400 copies/ml in 3 and <50 copies/ml in 11 countries. CONCLUSION There are important differences across Europe in national PMTCT guidelines, with most variation seen where the evidence-base remains limited. Such differences should be considered when interpreting research and surveillance findings.
Lano, a Novel LAP Protein Directly Connected to MAGUK Proteins in Epithelial Cells*

Protein networks asymetrically distributed to basolateral and apical epithelial membranes maintain cell polarity and homeostasis of epithelial tissues. Genetic studies in non-vertebrates assigned two families of basolateral proteins, MAGUK (membrane-associated and guanylatekinase) and LAP (leucine-rich repeatsand PDZ) proteins, to a common pathway crucial for the epithelial architecture and acting as a gatekeeper to malignancy. In mammals, three LAP proteins have been described, Densin-180, Erbin, and hScribble. Here, we identify a protein called Lano (LAP and no PDZ) only present in vertebrates and presenting strong identities with LAP proteins. Despite the lack of PDZ domain, Lano is located at the basolateral side of epithelial cells in a similar manner to Erbin and hScribble. Usingin vitro and in vivo experiments, we demonstrate that Lano directly interacts with the PDZ domains of MAGUK proteins, including hDLG (human disclarge), in epithelial cells. A second pool of Lano is complexed to Erbin. These LAP-MAGUK protein complexes coexist at the basolateral side of epithelial cells. We provide evidence for a direct interaction between LAP and MAGUK proteins, and we propose that various LAP-MAGUK networks targeted to the basolateral side of epithelial cells participate to homeostasis of epithelial tissues and tumor growth.
Comparative dynamic transcriptome analysis (cDTA) reveals mutual feedback between mRNA synthesis and degradation

To monitor eukaryotic mRNA metabolism, we developed comparative dynamic transcriptome analysis (cDTA). cDTA provides absolute rates of mRNA synthesis and decay in Saccharomyces cerevisiae (Sc) cells with the use of Schizosaccharomyces pombe (Sp) as an internal standard. cDTA uses nonperturbing metabolic labeling that supersedes conventional methods for mRNA turnover analysis. cDTA reveals that Sc and Sp transcripts that encode orthologous proteins have similar synthesis rates, whereas decay rates are fivefold lower in Sp, resulting in similar mRNA concentrations despite the larger Sp cell volume. cDTA of Sc mutants reveals that a eukaryote can buffer mRNA levels. Impairing transcription with a point mutation in RNA polymerase (Pol) II causes decreased mRNA synthesis rates as expected, but also decreased decay rates. Impairing mRNA degradation by deleting deadenylase subunits of the Ccr4–Not complex causes decreased decay rates as expected, but also decreased synthesis rates. Extended kinetic modeling reveals mutual feedback between mRNA synthesis and degradation that may be achieved by a factor that inhibits synthesis and enhances degradation.