Miracle-dz/UniFAR-FTUs huggingface dataset:
Essential Functional Role of the Polysaccharide Intercellular Adhesin of Staphylococcus epidermidis in Hemagglutination

ABSTRACT Hemagglutination of erythrocytes is a common property ofStaphylococcus epidermidis strains, which is related to adherence and biofilm formation and may be essential for the pathogenesis of biomaterial-associated infections caused byS. epidermidis. In three independent biofilm-producing, hemagglutination-positive S. epidermidis isolates, interruption of the icaADBC operon essential for polysaccharide intercellular adhesin (PIA) synthesis by Tn917 insertions led to a hemagglutination-negative phenotype. An immunoglobulin G fraction of antiserum to PIA greatly reduced hemagglutination. Purified PIA led to a 64-fold decrease of hemagglutination titers of these strains; however, it did not mediate hemagglutination by itself. These observations define PIA as the hemagglutinin of S. epidermidis or at least as its major functional component.
Binding of protein phosphatase 2A to the L-type calcium channel Cav1.2 next to Ser1928, its main PKA site, is critical for Ser1928 dephosphorylation.

The cAMP-dependent protein kinase (PKA) controls a large number of cellular functions. One critical PKA substrate in the brain and heart is the L-type Ca(2+) channel Ca(v)1.2, the activity of which is upregulated by PKA. The main PKA phosphorylation site is serine 1928 in the central pore forming alpha(1)1.2 subunit of Ca(v)1.2. PKA is bound to Ca(v)1.2 within a macromolecular signaling complex consisting of the beta(2) adrenergic receptor, trimeric G(s) protein, and adenylyl cyclase for fast, localized, and hence specific signaling [Davare, M. A. , Avdonin, V. , Hall, D. D. , Peden, E. M. , Buret, A. , Weinberg, R. J., Horne, M. C. , Hoshi, T. , and Hell, J. W. (2001) Science 293, 98-101]. Protein phosphatase 2A (PP2A) serves to effectively balance serine 1928 phosphorylation by PKA through its association with the Ca(v)1.2 complex [Davare, M. A. , Horne, M. C. , and Hell, J. W. (2000) J. Biol. Chem. 275, 39710-39717]. We now show that native PP2A holoenzymes, as well as the catalytic subunit itself, bind to alpha(1)1.2 immediately downstream of serine 1928. Of those holoenzymes, only heterotrimeric PP2A containing B' and B' ' subunits copurify with alpha(1)1.2. Preventing the binding of PP2A by truncating alpha(1)1.2 28 residues downstream of serine 1928 hampers its dephosphorylation in intact cells. Our results demonstrate for the first time that a stable interaction of PP2A with Ca(v)1.2 is required for effective reversal of PKA-mediated channel phosphorylation. Accordingly, PKA as well as PP2A are constitutively associated with Ca(v)1.2 for its proper regulation by phosphorylation and dephosphorylation of serine 1928.
Ethno-Cultural Variations in the Experience and Meaning of Mental Illness and Treatment: Implications for Access and Utilization

We conducted a study to investigate how understandings of mental illness and responses to mental health services vary along ethno-racial lines. Participants were 25 African American, Latino, and Euro-American inner-city residents in Hartford Connecticut diagnosed with severe mental illness and currently enrolled in a larger study of a community mental health center. Data were collected through 18 months of ethnographic work in the community. Overall, Euro-Americans participants were most aligned with professional disease-oriented perspectives on severe mental illness and sought the advice and counsel of mental health professionals. African-American and Latino participants emphasized non-biomedical interpretations of behavioral, emotional, and cognitive problems and were critical of mental health services. Participants across the sample expressed expectations and experiences of psychiatric stigma. Although Euro-Americans were aware of the risk of social rejection because of mental illness, psychiatric stigma did not form a core focus of their narrative accounts. By contrast, stigma was a prominent theme in the narrative accounts of African Americans, for whom severe mental illness was considered to constitute private “family business. ” For Latino participants, the cultural category of nervios appeared to hold little stigma, whereas psychiatric clinical labels were potentially very socially damaging. Our findings provide further empirical support for differences in symptom interpretation and definitions of illness among persons from diverse ethno-racial backgrounds. First-person perspectives on contemporary mental health discourses and practices hold implications for differential acceptability of mental health care that may inform variations in access and utilization of services in diverse populations.
Urban expansion detection with SPOT5 panchromatic images using textural features and PCA

Remote sensing is an effective tool in urban extent mapping and monitoring. In this study, a procedure to detect urban expansion is presented using SPOT5 panchromatic image with 2.5m resolution. First of all, the urban extents of different images are extracted with a PANTEX methodology, which use the anisotropic rotation-invariant textural grey-level co-occurrence measures as the presence of built-up areas. The change detection is performed on the two built-up index images using principal component analysis technique. Finally, the accuracy of this procedure is assessed with visual analysis results. The method shows good performance according to the overall accuracy of 91.18% (Kappa coefficient=0.8719).
Physical Layer Security with Untrusted Relays in Wireless Cooperative Networks

We investigate the problem of physical layer security in a wireless cooperative network, where communication is assisted by the untrusted relay. It is impossible for the amplify-and-forward protocol to convey a confidential message from the source to the destination without the help of other nodes, where only an untrusted relay is available. Nonetheless, our results are quite optimistic when there are multiple untrusted relays, which amplify the received signal and forward it to the destination. We treat the untrusted relay nodes as eavesdroppers, despite the fact that they are the enablers of communication. First of all, we prove that a positive secrecy rate can always be ensured regardless of the transmit power and the channel condition of the untrusted relays, as long as there exists a sufficient number of untrusted relays. Furthermore, a closed-form solution to the upper bound of secrecy rate is obtained. Finally, a practical approach is proposed to acquire a positive secrecy rate, which brings nearly no extra communication cost. Simulations are conducted to demonstrate the validity of the proposed approach.
Comparison of mental health between former child soldiers and children never conscripted by armed groups in Nepal.

CONTEXT Former child soldiers are considered in need of special mental health interventions. However, there is a lack of studies investigating the mental health of child soldiers compared with civilian children in armed conflicts. OBJECTIVE To compare the mental health status of former child soldiers with that of children who have never been conscripts of armed groups. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional cohort study conducted in March and April 2007 in Nepal comparing the mental health of 141 former child soldiers and 141 never-conscripted children matched on age, sex, education, and ethnicity. MAIN OUTCOME MEASURES Depression symptoms were assessed via the Depression Self Rating Scale, anxiety symptoms via the Screen for Child Anxiety Related Emotional Disorders, symptoms of posttraumatic stress disorder (PTSD) via the Child PTSD Symptom Scale, general psychological difficulties via the Strength and Difficulties Questionnaire, daily functioning via the Function Impairment tool, and exposure to traumatic events via the PTSD Traumatic Event Checklist of the Kiddie Schedule of Affective Disorders and Schizophrenia. RESULTS Participants were a mean of 15.75 years old at the time of this study, and former child soldiers ranged in age from 5 to 16 years at the time of conscription. All participants experienced at least 1 type of trauma. The numbers of former child soldiers meeting symptom cutoff scores were 75 (53.2%) for depression, 65 (46.1%) for anxiety, 78 (55.3%) for PTSD, 55 (39.0%) for psychological difficulties, and 88 (62.4%) for function impairment. After adjusting for traumatic exposures and other covariates, former soldier status was significantly associated with depression (odds ratio [OR], 2.41; 95% confidence interval [CI], 1.31-4.44) and PTSD among girls (OR, 6.80; 95% CI, 2.16-21.58), and PTSD among boys (OR, 3.81; 95% CI, 1.06-13.73) but was not associated with general psychological difficulties (OR, 2.08; 95% CI, 0.86-5.02), anxiety (OR, 1.63; 95% CI, 0.77-3.45), or function impairment (OR, 1.34; 95% CI, 0.84-2.14). CONCLUSION In Nepal, former child soldiers display greater severity of mental health problems compared with children never conscripted by armed groups, and this difference remains for depression and PTSD (the latter especially among girls) even after controlling for trauma exposure.
Differential Short-Term Plasticity at Convergent Inhibitory Synapses to the Substantia Nigra Pars Reticulata

Inhibitory projections from the striatum and globus pallidus converge onto GABAergic projection neurons of the substantia nigra pars reticulata (SNr). Based on existing structural and functional evidence, these pathways are likely to differentially regulate the firing of SNr neurons. We sought to investigate the functional differences in inhibitory striatonigral and pallidonigral traffic using whole-cell voltage clamp in brain slices with these pathways preserved. We found that striatonigral IPSCs exhibited a high degree of paired-pulse facilitation. We tracked this facilitation over development and found the facilitation as the animal aged, but stabilized by postnatal day 17 (P17), with a paired pulse ratio of 2. We also found that the recovery from facilitation accelerated over development, again, reaching a stable phenotype by P17. In contrast, pallidonigral synapses show paired-pulse depression, and this depression could be solely explained by presynaptic changes. The mean paired-pulse ratio of 0.67 did not change over development, but the recovery from depression slowed over development. Pallidonigral IPSCs were significantly faster than striatonigral IPSCs when measured at the soma. Finally, under current clamp, prolonged bursts of striatal IPSPs were able to consistently silence the pacemaker activity of nigral neurons, whereas pallidal inputs depressed, allowing nigral neurons to reinstate firing. These findings highlight the importance of differential dynamics of neurotransmitter release in regulating the circuit behavior of the basal ganglia.
On the Long-Run Calibration of the Credit-to-Gdp Gap as a Banking Crisis Predictor

The trend deviation of the Credit-to-GDP ratio (“Basel gap”) is a widely used early warning indicator of banking crises. It is calculated with the one-sided Hodrick-Prescott filter using an extremely large value of the smoothing parameter λ. We recalibrate the smoothing parameter with panel data covering almost one and a half centuries and 15 countries. The optimal λ is found to be much lower than previously suggested. The 2008 crisis does not dominate the results. The long sample almost eliminates filter initialisation problems.
Clonally variant gene families in Plasmodium falciparum share a common activation factor

The genome of the malaria parasite Plasmodium falciparum contains several multicopy gene families, including var, rifin, stevor and Pfmc‐2TM. These gene families undergo expression switching and appear to play a role in antigenic variation. It has recently been shown that forcing parasites to express high copy numbers of transcriptionally active, episomal var promoters led to gradual downregulation and eventual silencing of the entire var gene family, suggesting that a limiting titratable factor plays a role in var gene activation. Through similar experiments using rifin, stevor or Pfmc‐2TM episomal promoters we show that promoter titration can be used as a general method to downregulate multicopy gene families in P. falciparum. Additionally, we show that promoter titration with var, rifin, stevor or Pfmc‐2TM episomal promoters results in downregulation of expression not only of the family to which the episomal promoter belongs, but also members of the other gene families, suggesting that the var‐specific titratable factor previously described is shared by all four families. Further, transcriptionally active promoters from different families colocalize within the same subnuclear expression site, indicating that the role that nuclear architecture plays in var gene regulation also likely applies to the other multicopy gene families of P. falciparum.
A forest-based approach to identifying gene and gene–gene interactions

Multiple genes, gene-by-gene interactions, and gene-by-environment interactions are believed to underlie most complex diseases. However, such interactions are difficult to identify. Although there have been recent successes in identifying genetic variants for complex diseases, it still remains difficult to identify gene–gene and gene–environment interactions. To overcome this difficulty, we propose a forest-based approach and a concept of variable importance. The proposed approach is demonstrated by simulation study for its validity and illustrated by a real data analysis for its use. Analyses of both real data and simulated data based on published genetic models show the effectiveness of our approach. For example, our analysis of a published data set on age-related macular degeneration (AMD) not only confirmed a known genetic variant (P value = 2E-6) for AMD, but also revealed an unreported haplotype surrounding single-nucleotide polymorphism (SNP) rs10272438 on chromosome 7 that was significantly associated with AMD (P value = 0.0024). These significance levels are obtained after the consideration for a large number of SNPs. Thus, the importance of this work is twofold: it proposes a powerful and flexible method to identify high-risk haplotypes and their interactions and reveals a potentially protective variant for AMD.
Prenatal diagnosis of myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome: contribution to understanding mitochondrial DNA segregation during human embryofetal development

Introduction: Myopathy, encephalopathy, lactic acidosis, and stroke-like (MELAS) syndrome, a maternally inherited disorder that is among the most common mitochondrial DNA (mtDNA) diseases, is usually associated with the m.3242A>G mutation of the mitochondrial tRNAleu gene. Very few data are available with respect to prenatal diagnosis of this serious disease. The rate of mutant versus wild-type mtDNA (heteroplasmy) in fetal DNA is indeed considered to be a poor indicator of postnatal outcome. Materials and methods: Taking advantage of a novel semi-quantitative polymerase chain reaction test for m.3243A>G mutant load assessment, we carried out nine prenatal diagnoses in five unrelated women, using two different fetal tissues (chorionic villi v amniocytes) sampled at two or three different stages of pregnancy. Results: Two of the five women, although not carrying m.3243A>G in blood or extra-blood tissues, were, however, considered at risk for transmission of the mutation, as they were closely related to MELAS-affected individuals. The absence of 3243A>G in the blood of first degree relatives was associated with no mutated mtDNA in the cardiovascular system (CVS) or amniocytes, and their three children are healthy, with a follow-up of 3 months–3 years. Among the six fetuses from the three carrier women, three were shown to be homoplasmic (0% mutant load), the remaining three being heteroplasmic, with a mutant load ranging from 23% to 63%. The fetal mutant load was fairly stable at two or three different stages of pregnancy in CVS and amniocytes. Although pregnancy was terminated in the case of the fetus with a 63% mutant load, all other children are healthy with a follow-up of 3 months–6 years. Conclusion: These data suggest that a prenatal diagnosis for MELAS syndrome might be helpful for at-risk families.
Knowledge Management Diagnosis in Vojvodina Firms by Using Bukowitz and Williams Model

Osnovna svrha ovog rada je da empirijski analizira stanje menadžmenta znanja (KM) u jednom određenom regionu. U cilju procene stanja preduzeca u Vojvodini u pogledu primene KM programa, primenjen je dijagnosticki model upravljanja znanjem. Hipoteze zasnovane na specificnom integrisanom setu KM su definisane i statisticki testirane na uzorku od 190 vojvođanskih kompanija iz razlicitih industrija, državnih institucija i javnih preduzeca. Koriscen je metod anketiranja u cilju prikupljanja podataka o praksi KM i drugim srodnim organizacijskim aspektima. Rezultati istraživanja pokazuju stepen do kojeg pojedinacni koraci KM na celom uzorku odstupaju od maksimalne dodeljene vrednosti. Ovo istraživanje pruža osnovu za prakticiranje inženjerskih menadžera da bi lakse pozicionirali kompaniju i prepoznali korake KM koji se mogu poboljsati kako bi se postigla strateska vrednost i zatvorio jaz između prosecne i maksimalne vrednosti dodijeljene za svaki korak .
An Anti-GDNF Family Receptor Alpha 1 (GFRA1) Antibody–Drug Conjugate for the Treatment of Hormone Receptor–Positive Breast Cancer

Luminal A (hormone receptor-positive) breast cancer constitutes 70% of total breast cancer patients. In an attempt to develop a targeted therapeutic for this cancer indication, we have identified and characterized Glial cell line–Derived Neurotrophic Factor (GDNF) Family Receptor Alpha 1 (GFRA1) antibody–drug conjugates (ADC) using a cleavable valine-citrulline-MMAE (vcMMAE) linker-payload. RNAseq and IHC analysis confirmed the abundant expression of GFRA1 in luminal A breast cancer tissues, whereas minimal or no expression was observed in most normal tissues. Anti–GFRA-vcMMAE ADC internalized to the lysosomes and exhibited target-dependent killing of GFRA1-expressing cells both in vitro and in vivo. The ADCs using humanized anti-GFRA1 antibodies displayed robust therapeutic activity in clinically relevant cell line–derived (MCF7 and KPL-1) tumor xenograft models. The lead anti-GFRA1 ADC cross-reacts with rodent and cynomolgus monkey GFRA1 antigen and showed optimal pharmacokinetic properties in both species. These properties subsequently enabled a target-dependent toxicity study in rats. Anti-GFRA1 ADC is well tolerated in rats, as seen with other vcMMAE linker–payload based ADCs. Overall, these data suggest that anti–GFRA1-vcMMAE ADC may provide a targeted therapeutic opportunity for luminal A breast cancer patients. Mol Cancer Ther; 17(3); 638–49. ©2017 AACR.
DNA-binding activities of the Drosophila melanogaster even-skipped protein are mediated by its homeo domain and influenced by protein context

The homeo box gene even-skipped (eve) encodes a 376-amino-acid protein that binds with high affinity to sequences located near the 5' termini of the eve and en genes. The 5' en sites are A + T rich and contain copies of the 10-base-pair (bp) consensus sequence T-C-A-A-T-T-A-A-A-T. In contrast, the 5' eve sites are G + C rich and contain the 9-bp sequence T-C-A-G-C-A-C-C-G. Among the five different homeo box proteins that have been tested for binding, eve is unique in that it shows virtually equal preference for the A + T-rich 5' en binding sites and the G + C-rich 5' eve sites. Most of the other proteins bind with a relatively higher affinity to the en sites than to the eve sites. In an effort to identify the regions of the eve protein that are responsible for its efficient binding to both classes of recognition sequences, we analyzed the DNA-binding properties of various mutant eve proteins. These studies suggest that the homeo domain of the eve protein is responsible for both binding activities. However, mutations in distant regions of the protein influenced the binding behavior of the eve homeo domain and caused a reduction in binding to the G + C class of recognition sites. We propose that the protein context of the homeo domain can influence its DNA-binding properties.
Using real-time fMRI neurofeedback to restore right occipital cortex activity in patients with left visuo-spatial neglect: proof-of-principle and preliminary results

ABSTRACT Hemineglect is common after right parietal stroke, characterised by impaired awareness for stimuli in left visual space, with suppressed neural activity in the right visual cortex due to losses in top-down attention signals. Here we sought to assess whether hemineglect patients are able to up-regulate their right visual cortex activity using auditory real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback. We also examined any effect of this training procedure on neglect severity. Two different neurofeedback methods were used. A first group of six patients was trained to up-regulate their right visual cortex activity and a second group of three patients was trained to control interhemispheric balance between their right and left visual cortices. Over three sessions, we found that the first group successfully learned to control visual cortex activity and showed mild reduction in neglect severity, whereas the second group failed to control the feedback and showed no benefit. Whole brain analysis further indicated that successful up-regulation was associated with a recruitment of bilateral fronto-parietal areas. These findings provide a proof of concept that rt-fMRI neurofeedback may offer a new approach to the rehabilitation of hemineglect symptoms, but further studies are needed to identify effective regulation protocols and determine any reliable impact on clinical symptoms.
Nuclear Accumulation of cRel following C-Terminal phosphorylation by TBK1/IKKε1

The NF-κB transcription factors are key regulators of immunomodulatory, cell cycle, and developmental gene regulation. NF-κB activity is mainly regulated through the phosphorylation of IκB by the IκB kinase (IKK) complex IKKαβγ, leading to proteasome-mediated degradation of IκB, nuclear translocation of NF-κB dimers, DNA binding, and gene induction. Additionally, direct posttranslational modifications of NF-κB p65 and cRel subunits involving C-terminal phosphorylation has been demonstrated. The noncanonical IKK-related homologs, TNFR-associated factor family member-associated NF-κB activator (TANK)-binding kinase (TBK)1 and IKKε, are also thought to play a role in NF-κB regulation, but their functions remain unclear. TBK1 and IKKε were recently described as essential regulators of IFN gene activation through direct phosphorylation of the IFN regulatory factor-3 and -7 transcription factors. In the present study, we sought to determine whether IKKε and TBK1 could modulate cRel activity via phosphorylation. TBK1 and IKKε directly phosphorylate the C-terminal domain of cRel in vitro and in vivo and regulate nuclear accumulation of cRel, independently of the classical IκB/IKK pathway. IκBα degradation is not affected, but rather IKKε-mediated phosphorylation of cRel leads to dissociation of the IκBα-cRel complex. These results illustrate a previously unrecognized aspect of cRel regulation, controlled by direct IKKε/TBK1 phosphorylation.