Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Role for Wnt/Ca2+ Signaling in Actin Cytoskeleton Remodeling and Cell Motility in Prostate Cancer

Wnt signaling is a critical regulatory pathway in development and disease. Very little is known about the mechanisms of Wnt signaling in prostate cancer, a leading cause of death in men. A quantitative analysis of the expression of Wnt5A protein in human tissue arrays, containing 600 prostate tissue cores, showed >50% increase in malignant compared to benign cores (p<0.0001). In a matched pair of prostate cancer and normal cell line, expression of Wnt5A protein was also increased. Calcium waves were induced in prostate cells in response to Wnt5A with a 3 fold increase in Flou-4 intensity. The activity of Ca2+/calmodulin dependent protein kinase (CaMKII), a transducer of the non-canonical Wnt/Ca2+ signaling, increased by 8 fold in cancer cells; no change was observed in β-catenin expression, known to activate the canonical Wnt/β-catenin pathway. Mining of publicly available human prostate cancer oligoarray datasets revealed that the expression of numerous genes (e.g., CCND1, CD44) under the control of β-catenin transcription is down-regulated. Confocal and quantitative electron microscopy showed that specific inhibition of CaMKII in cancer cells causes remodeling of the actin cytoskeleton, irregular wound edges and loose intercellular architecture and a 6 and 8 fold increase in the frequency and length of filopodia, respectively. Conversely, untreated normal prostate cells showed an irregular wound edge and loose intercellular architecture; incubation of normal prostate cells with recombinant Wnt5A protein induced actin remodeling with a regular wound edge and increased wound healing capacity. Live cell imaging showed that a functional consequence of CaMKII inhibition was 80% decrease in wound healing capacity and reduced cell motility in cancer cells. We propose that non-canonical Wnt/Ca2+ signaling via CaMKII acts as a novel regulator of structural plasticity and cell motility in prostate cancer.
Quantitative myocardial perfusion magnetic resonance imaging: the impact of pulsatile flow on contrast agent bolus dispersion

Myocardial blood flow (MBF) can be quantified using T1-weighted first-pass magnetic resonance imaging (MRI) in combination with a tracer-kinetic model, like MMID4. This procedure requires the knowledge of an arterial input function which is usually estimated from the left ventricle (LV). Dispersion of the contrast agent bolus may occur between the LV and the tissue of interest. The aim of this study was to investigate the dispersion under conditions of physiological pulsatile blood flow, and to simulate its effect on MBF quantification. The dispersion was simulated in coronary arteries using a computational fluid dynamics (CFD) approach. Simulations were accomplished on straight vessels with stenosis of different degrees and shapes. The results show that dispersion is more pronounced under resting conditions than during hyperemia. Stenosis leads to a reduction of dispersion. In consequence, dispersion results in a systematic MBF underestimation between −0.4% and −9.3%. The relative MBF error depends not only on the dispersion but also on the actual MBF itself. Since MBF under rest is more underestimated than under stress, myocardial perfusion reserve is overestimated between 0.1% and 4.5%. Considering other sources of errors in myocardial perfusion MRI, systematic errors of MBF by bolus dispersion are relatively small.
Archaeal Homolog of Bacterial Type IV Prepilin Signal Peptidases with Broad Substrate Specificity

ABSTRACT A large number of secretory proteins in the thermoacidophile Sulfolobus solfataricus are synthesized as a precursor with an unusual leader peptide that resembles bacterial type IV prepilin signal sequences. This set of proteins includes the flagellin subunit but also various solute binding proteins. Here we describe the identification of the S. solfataricus homolog of bacterial type IV prepilin peptidases, termed PibD. PibD is an integral membrane protein that is phylogenetically related to the bacterial enzymes. When heterologously expressed in Escherichia coli, PibD is capable of processing both the flagellin and glucose-binding protein (GlcS) precursors. Site-directed mutagenesis of the GlcS signal peptide shows that the substrate specificity of PibD is consistent with the variations found in proteins with type IV prepilin-like signal sequences of S. solfataricus. We conclude that PibD is responsible for the processing of these secretory proteins in S. solfataricus.
The effects of gender on health‐related quality of life in pediatric live‐donor kidney transplantation: A single‐center experience in a developing country

El‐Husseini A, Hassan R, Sobh M, Ghoneim M. The effects of gender on health‐related quality of life in pediatric live‐donor kidney transplantation: A single‐center experience in a developing country. Pediatr Transplantation 2010:14:188–195. © 2009 John Wiley & Sons A/S.
Silence AIDS and sexual culture in Africa -- a tribute to womens month 2000.

This paper discusses the inter-relatedness of silence AIDS and sexual culture in Africa. It is noted that the crux of the AIDS epidemic in the region is the stubborn and multi-layered AIDS silence. This form of denial has consistently characterized the AIDS epidemic in the region from the very beginning. It is suggested that this silence has much to do with heterosexual power and sexual lifeways the structure and meanings of which are influenced by culture. In three related stories which evince the hopeless situation of women in the face of AIDS it is indicated that women are being squashed under the weight of the compounded multiple silences of AIDS. Although efforts addressing this issue such as the AIDS 2000 “Break The Silence” Conference have been implemented no change in behavior among South Africans was noted. Studies have shown that there is an urgent need to recognize and accept the nature and shape of contemporary sexual mores that have dire consequences in the wake of AIDS. Men need to change their attitudes and behaviors that reflect their sexual irresponsibility and African leaders should implement firm measures to foster the transformation of the sexual attitudes and practices of young and middle-aged men.
Recent Developments in Drug Therapy for Aplastic Anemia

Objective: This article reviews recent developments in immunosuppressive therapy (IST) for aplastic anemia (AA) patients who are not candidates for stem cell transplant (SCT); including, front-line, salvage, and novel treatment options with a focus on response rates (RRs) and overall survival (OS). Data Sources: A PubMed literature search was performed from 1977 to June 2014 using the search terms aplastic anemia, horse antithymocyte globulin (hATG), rabbit ATG (rATG), thymoglobulin, and cyclosporine (CSA). Additional references were identified from a review of literature citations. Study Selection and Data Extraction: All English-language studies investigating IST for treatment of AA in non–SCT candidates were evaluated. Data Synthesis: Studies indicate addition of CSA and corticosteroids to hATG for treatment of AA improves RRs, decreases relapse rates, and improves 5-year OS. hATG improved RRs, relapse rates, and OS compared to rATG in the front-line setting. Studies support the use of rATG when front-line IST with hATG fails or when hATG is unavailable. Front-line daclizumab can be considered for nonsevere AA (NAA); however, data is limited. Alemtuzumab or eltrombopag are options for relapsed AA in select patients. Conclusions: hATG with methylprednisolone and CSA is recommended for front-line treatment of AA, whereas rATG is reserved for salvage therapy. Front-line use of daclizumab has been studied in NAA patients, but additional prospective trials are needed before this is adopted into clinical practice. Alemtuzumab and eltrombopag have been studied for treatment of AA; recruiting is ongoing in clinical trials to assess the appropriate dosing strategy and place in therapy.
Action and Information in the Job Mobility Process: The Search Decision

Current sociological models of job mobility suppress the intervening action and information mechanisms that link structural constraints to job shifts. To remedy this, this paper joins core features of structural-mobility models to key elements of economic approaches to job change in an analysis of the employed worker's decision to search the market for a better job. The analysis highlights the complementarity of structural and action approaches by conceptualizing the forces governing the search decision in terms of the principal dimensions-opportunities and achievement gains-underlying job-mobility models. The basic framework is extended to include the quality of a worker's initial screen of a prospective job as a mechanism that promotes search. The concepts of opportunities, gains, and screen quality are then used to explain male-female differences in mobility orientations. The empirical findings both reinforce structuralist assumptions and underscore the promise of applying to the study of mobility processes the kind of action approach recently advocated by Coleman (1986).
Ibrutinib Inhibits VLA-4–Dependent Adhesion in CLL—Reply

We thank Zucchetto and colleagues for their valuable comments on our article (1). They make two points: first, in their hands, in contrast to our report, inhibition of integrin b-1 (CD29) and integrin a-4 (CD49d) was equally effective in reducing chronic lymphocytic leukemia (CLL) cell adhesion. Repeating our original assay (Fig. 5B) with three anti-CD29 antibodies (clones: 4B7R, P5D2, and P4G11; R&D Systems), we found that our experiments may have underestimated the effect of CD29 blockade on cell adhesion, confirming the findings by Zucchetto and colleagues. However, for each of the clones, there was considerable interpatient and interclonal variability in the effect size. Second, Zucchetto and colleagues note that ibrutinib in vitro reduced but did not abolish adhesion. The results of in vitro assays presented in our Supplementary Fig. S2A and S2B are in agreement with this conclusion (1). In contrast, in vivo, ibrutinib abrogated the ability of CLL cells to adhere to fibronectin as measured in ex vivo assays with cells obtained from patients on day 28 of ibrutinib treatment (Fig. 2A and B; ref. 1). This appears to be the result of cumulative drug exposure, given that adhesion of cells collectedonday2, after just onedose of ibrutinib,wasonly partially inhibited (1). Thus, treatment with ibrutinib in vivo has a much stronger inhibitory effect on cell adhesion then captured by experiments (both ours and Zucchetto and colleagues') that drug cells in vitro. We used samples from patients treated with single-agent ibrutinib to investigate the basis for our previous observation that upon starting ibrutinib treatment, most patients develop a transient rise in absolute lymphocyte count that is due to the release of cells from the lymph node (2). VLA-4–dependent adhesion is regulated by chemokines and B-cell receptor (BCR) signaling, referred to as "inside-out signaling," affecting both conformation (PKC/DAG dependent) and substrate affinity (IP3/Caþ dependent) of the integrin (3). BCR signaling and chemokine binding occur primarily in the microenvironment of the secondary lymphoid tissues. In vivo, ibrutinib potently inhibits BCR and chemokine signaling (4, 5). We posit that sustained in vivo inhibition of inside-out signaling leads to more profound changes in VLA-4 function than short-term drugging of cells in vitro, resulting in a more profound reduction in integrin-mediated adhesion. Future experiments could address this hypothesis and we thank Zucchetto and colleagues for suggesting a tool that could be used to evaluate changes in VLA-4 confirmation and affinity.
Changes in nutrition type between generations influence on bone structural changes in female offspring

Background and Purpose: It is believed that changes in feeding protocol between generations have influence on the balance of the whole organism. Epidemiological studies suggest that skeletal growth is programmed during intrauterine and early postnatal life. The aim of the study was to determinate impact of maternal dietary fat excess and nutrition of female offspring on the bone structural changes in latter. Materials and Methods: Ten female Sprague Dawley rats were randomly divided in two groups. One group was fed with high content of saturated fatty acid food (HFD) and the other with standard laboratory chow (CD). Offspring from both groups were randomly divided in two subgroups after coupling and lactation period, subsequently there were four groups of offspring (n=6 each) with different feeding protocol: a) CD-CD – control diet mothers and offspring, b) CD-HFD – control diet mothers and high fat diet offspring, c) HFD-CD – high fat diet mothers and control diet offspring and d) HFD-HFD – high fat diet mothers and offspring. At the age of 18 weeks in female offspring bone microstructure was analyzed in fifth lumbar vertebra using digital photographic images. Results and Conclusions: The control diet female offspring of high fat fed mothers showed the highest values of trabecular thickness and trabecular number, while the CD-HFD offspring group had the highest values of trabecular separation and cortical thickness. Maternal nutritional status affects the future development of offspring.
[Sinusitis in long-term intubated, intensive care patients: nasal versus oral intubation].

UNLABELLED Discussion of paranasal sinusitis as a nosocomial infection in the mechanically ventilated intensive care (ICU) patient has recently been intensified. Some authors have emphasized nasotracheal intubation as a possible pathogenetic pathway. The aim of this study was to investigate the impact of nasotracheal or orotracheal intubation on the development of sinusitis in ICU patients. METHODS In a prospective study, we followed 44 patients who required mechanical ventilation (greater than 24 h) in the ICU because of prolonged recovery from abdominal, thoracic, or posttraumatic surgery. Twenty patients were intubated nasotracheally and 24 orotracheally. Assignment to the groups was random. All were provided with a nasogastric tube and initially treated with systemic antibiotics. They received local antimicrobial prophylaxis of the nose, oropharynx, and stomach. Daily a-scan examinations of the maxillary sinuses were performed from the day of admission to the ICU until extubation, tracheotomy, death, or transfer. The average observation period was 6.9 days in the oral group and 7.1 days in the nasal group. In the case of a pathologic finding, aspiration of the antral sinus was carried out. In this study sinusitis indicated a sonographic finding; it did not necessarily imply a bacterial infection. RESULTS At the beginning of the observation period, 6 patients in the oral group and 4 in the nasal group already had a pathologic maxillary sinus finding. At the end, in 15 of 24 in the oral group and 19 of 20 in the nasal group unilateral or bilateral sinusitis could be demonstrated. Development of bilateral sinusitis (13/20 in the nasotracheal group, 8/24 in the orotracheal group) was mainly observed after the appearance of unilateral sinusitis. The site corresponded to the site of the nasal tube in 65%. Unilateral paranasal infection was observed in nasotracheally and orotracheally intubated patients after an average of 2.8 and 2.6 days, respectively, whereas bilateral sinusitis had an average time delay of 4.5 and 5.7 days. Aspiration of the maxillary sinus was performed in 22 of 34 cases with sinusitis. Pathogenic organisms could be demonstrated in 7 of 13 nasotracheally intubated patients but only 2 of 9 with orotracheal tubes. CONCLUSION We found that patients intubated orotracheally developed significantly less sinusitis than those intubated nasotracheally. Edema, local infection of the nasal mucosa, or mechanical obstruction of sinus drainage pathways by the tube are possible explanations. The fact that 63% of orally intubated patients had a pathologic maxillary sinus finding as well suggests that in addition to other reasons, an increased central venous pressure, positive pressure ventilation, and the supine position must be regarded as predisposing factors that increase the incidence of sinusitis. We conclude that the conditions of critically ill patients predispose to the development of sinusitis. Nasotracheal intubation is to be regarded as an additional risk, and therefore oral intubation should be preferred.
The Permeabilizing ATP Receptor, P2X7

A cDNA was isolated from a human monocyte library that encodes the P2X7 receptor; the predicted protein is 80% identical to the rat receptor. Whole cell recordings were made from human embryonic kidney cells transfected with the human cDNA and from human macrophages. Brief applications (1-3 s) of ATP and 2′,3′-(4-benzoyl)-benzoyl-ATP elicited cation-selective currents. When compared with the rat P2X7 receptor, these effects required higher concentrations of agonists, were more potentiated by removal of extracellular magnesium ions, and reversed more rapidly on agonist removal. Longer applications of agonists permeabilized the cells, as evidenced by uptake of the propidium dye YO-PRO1, but this was less marked than for cells expressing the rat P2X7 receptor. Expression of chimeric molecules indicated that some of the differences between the rat and human receptor could be reversed by exchanging the intracellular C-terminal domain of the proteins.
The use of respiratory variations in right atrial pressure to predict the cardiac output response to PEEP.

PURPOSE The purpose of this study was to determine whether the pattern of respiratory variation in right atrial pressure (Pra) predicts the cardiac output response to positive end-expiratory pressure (PEEP). MATERIALS AND METHODS We studied 18 patients with a variety of cardiac and pulmonary disorders requiring ventilatory support. A pulmonary artery flotation catheter was in place as part of their routine management. Changes in PEEP were made from 0 to 14 cm H2O to determine the level of PEEP, which increased PO(2) without decreasing cardiac output (ie, assessment of best PEEP). Static lung compliance and auto-PEEP were obtained from the pressure signal on the ventilator. The change in Pra with a spontaneous inspiratory effort (ie, triggered breath) was used to determine whether patients had a restrictive (ie, operating on the flat part of the Starling curve), or nonrestrictive pattern (acting on the ascending part of the Starling curve) as previously described. RESULTS Cardiac output decreased 0.7 +/- 0.8 L/min (change from baseline P <.05) in the group with an inspiratory decrease in Pra and -0.04 +/- 1.50 L/min (P = NS) in the group without an inspiratory decrease in Pra. The groups were not significantly different. However, the variance in cardiac output was large and, in contrast to our hypothesis, two patients in the group with an inspiratory decrease in Pra did not have a decrease in cardiac output. Pra and pulmonary artery occlusion pressure after the PEEP trial were greater than before, indicating that reflex circulatory adjustments occurred in response to the PEEP. CONCLUSIONS The inspiratory pattern in Pra does not predict the response to cardiac output to PEEP in individual patients. This is most likely because of reflex adaptations in the circuit that occur with the application of PEEP. The response of a patient to PEEP is affected by the patient's volume reserves, filling status of the right atrium, and neurosympathetic activity.
User and home appliances pervasive interaction in a sensor driven smart home environment: The SandS approach

EU FIRE research project "Social and Smart" aims to formalize and build a complete ecosystem of users, context sensors and smart home appliances that interact following the ubiquitous computing paradigm in order to adapt and enhance the everyday user-appliance interaction. In this framework a user is modeled through the use of Personas stereotypes. Contextual information is collected via wireless ambient sensors, such as temperature and humidity ones, but can also include Smart City sensors and services. This contextual information is further re-lated to each user's model through the enforcement of home rules, expressed in a high level language. Knowledge representation is supported through Semantic Web technologies that also ensure the interoperability between all the actors of the ecosystem. Preliminary experimental results have been carried in a small scale Smart Home setting, but also in a larger scale using the FIWARE1 framework provided by the SmartSandander testbed.
Reading frame switch caused by base‐pair formation between the 3′ end of 16S rRNA and the mRNA during elongation of protein synthesis in Escherichia coli.

Watson‐Crick base pairing is shown to occur between the mRNA and nucleotides near the 3′ end of 16S rRNA during the elongation phase of protein synthesis in Escherichia coli. This base‐pairing is similar to the mRNA‐rRNA interaction formed during initiation of protein synthesis between the Shine and Dalgarno (S‐D) nucleotides of ribosome binding sites and their complements in the 1540‐1535 region of 16S rRNA. mRNA‐rRNA hybrid formation during elongation had been postulated to explain the dependence of an efficient ribosomal frameshift on S‐D nucleotides precisely spaced 5′ on the mRNA from the frameshift site. Here we show that disruption of the postulated base pairs by single nucleotide substitutions, either in the S‐D sequence required for shifting or in nucleotide 1538 of 16S rRNA, decrease the amount of shifting, and that this defect is corrected by restoring complementary base pairing. This result implies that the 3′ end of 16S rRNA scans the mRNA very close to the decoding sites during elongation.
Impact of the Fragile X mental retardation 1 (FMR1) gene premutation on neuropsychiatric functioning in adult males without fragile X‐associated Tremor/Ataxia syndrome: A controlled study

Fragile X Syndrome is the most common heritable form of mental retardation caused by silencing of the FMR1 gene, which arises from intergenerational trinucleotide repeat expansion leading to full mutation. An intermediary carrier condition, known as the premutation, is characterized by expansion up to 200 repeats without concomitant gene silencing. This prevalent allelic variant was initially thought to be free of phenotypic effects. However, recent reports have identified a degenerative disease, Fragile X‐associated Tremor/Ataxia Syndrome (FXTAS) in older men as well as premature ovarian failure in women. Previously reports are inconsistent regarding the neuropsychiatric phenotype associated with premutation due to small sample sizes, ascertainment bias, lack of adequate control groups, administration of measures with poor psychometric properties, and the confounding effects of FXTAS. We addressed these problems by conducting a controlled study of male carriers (n = 40) of the premutation without manifest symptoms of FXTAS, comparing their responses on specific, reliable, and valid measures of neuropsychiatric functioning to those of individuals with shared family environment (n = 22) and non‐carrier comparison males (n = 43). Multivariate analyses revealed that the premutation confers significant risk for working memory difficulties, an associated feature of Attention‐Deficit Disorder. Furthermore, both the family controls and men with premutation exhibited higher rates of Alcohol Abuse as compared to non‐carrier control men. These findings highlight the importance of recognizing the distinct phenotypic outcomes that characterize the Fragile X premutation and the subtle risk factors that can act as precursors to more significant psychiatric impairment. © 2007 Wiley‐Liss, Inc.