Miracle-dz/UniFAR-FTUs huggingface dataset:
PP2A binds to the LIM domains of lipoma-preferred partner through its PR130/B″ subunit to regulate cell adhesion and migration

ABSTRACT Here, we identify the LIM protein lipoma-preferred partner (LPP) as a binding partner of a specific protein phosphatase 2A (PP2A) heterotrimer that is characterised by the regulatory PR130/B″α1 subunit (encoded by PPP2R3A). The PR130 subunit interacts with the LIM domains of LPP through a conserved Zn2+-finger-like motif in the differentially spliced N-terminus of PR130. Isolated LPP-associated PP2A complexes are catalytically active. PR130 colocalises with LPP at multiple locations within cells, including focal contacts, but is specifically excluded from mature focal adhesions, where LPP is still present. An LPP–PR130 fusion protein only localises to focal adhesions upon deletion of the domain of PR130 that binds to the PP2A catalytic subunit (PP2A/C), suggesting that PR130–LPP complex formation is dynamic and that permanent recruitment of PP2A activity might be unfavourable for focal adhesion maturation. Accordingly, siRNA-mediated knockdown of PR130 increases adhesion of HT1080 fibrosarcoma cells onto collagen I and decreases their migration in scratch wound and Transwell assays. Complex formation with LPP is mandatory for these PR130-PP2A functions, as neither phenotype can be rescued by re-expression of a PR130 mutant that no longer binds to LPP. Our data highlight the importance of specific, locally recruited PP2A complexes in cell adhesion and migration dynamics. Highlighted Article: The importance of localised regulation of protein dephosphorylation in cell adhesion and migration through demonstration of a new interaction between the LIM protein LPP and PP2A comprising the Bʹʹ/PR130 subunit.
Human C5a Protein Participates in the Mosquito Immune Response Against Dengue Virus

Abstract Dengue virus (DENV) is transmitted by Aedes spp mosquitoes during a bloodmeal uptake. The bloodmeal consists of host cells, immune factors, and possibly blood-borne pathogens, such as arboviruses. Human cells and immune-related factors, like the complement system, can remain active in the bloodmeal and may be able to interact with pathogens in the mosquito. Previous studies have shown that active complement proteins impact Plasmodium parasite viability in the Anopheles midgut. Thus, we investigated the effects of the human complement on DENV infection in the midgut of Aedes aegypti. Our findings indicate that mosquitoes receiving DENV mixed with normal non-inactivated human serum showed significantly lower viremia than those fed with heat-inactivated serum. This implies that human complement may act to limit DENV infection in the mosquito midgut. In addition, we found that human complement C5a protein was able to directly communicate with mosquito cells, affecting the cell antiviral response against DENV. Our results also show that human C5a protein is able to interact with several membrane-bound mosquito proteins. Together these results suggest an important role of human complement protein in DENV transmission.
Methylation Status of H19/IGF2 Differentially Methylated Region in in vitro Human Blastocysts Donated by Healthy Couples

Background: Imprinted genes are a unique subset of few genes that have been differentially methylated region (DMR) in a parental origin-dependent manner during gametogenesis, and these genes are highly protected during pre-implantation epigenetic reprogramming. Several studies have shown that the particular vulnerability of imprinting genes during suboptimal pre- and peri-conception micro-environments often is occurred by assisted reproduction techniques (ART). This study investigated the methylation status of H19/IGF2 DMR at high-quality expanding/expanded human blastocysts donated by healthy individuals to evaluate the risks linked to ART. Method: Methylation levels of H19/IGF2 DMR were analyzed by bisulfite conversion and sequencing at 18 CpG sites (CpGs) located in this region. Result: The overall percentage of methylated CpGs and the proportion of hyper-methylated clones of H19/IGF2 DMR in analyzed blastocysts were 37.85±4.87% and 43.75±5.1%, respectively. For validation of our technique, the corresponding methylation levels of peripheral human lymphocytes were defined (49.52±1.86% and 50%, respectively). Conclusion: Considering the absence of in vivo- produced human embryos, it is not possible to conclude that the methylation found in H19/IGF2 DMR is actually normal or abnormal. Regarding the possible risks associated with ART, the procedures should be optimized in order to at least reduce some of the epigenetic risks.
Cross Talk between Activation and Slow Inactivation Gates of Shaker Potassium Channels

This study addresses the energetic coupling between the activation and slow inactivation gates of Shaker potassium channels. To track the status of the activation gate in inactivated channels that are nonconducting, we used two functional assays: the accessibility of a cysteine residue engineered into the protein lining the pore cavity (V474C) and the liberation by depolarization of a Cs+ ion trapped behind the closed activation gate. We determined that the rate of activation gate movement depends on the state of the inactivation gate. A closed inactivation gate favors faster opening and slower closing of the activation gate. We also show that hyperpolarization closes the activation gate long before a channel recovers from inactivation. Because activation and slow inactivation are ubiquitous gating processes in potassium channels, the cross talk between them is likely to be a fundamental factor in controlling ion flux across membranes.
Ceramide–Antiestrogen Nanoliposomal Combinations—Novel Impact of Hormonal Therapy in Hormone-Insensitive Breast Cancer

Although the sphingolipid ceramide exhibits potent tumor suppressor effects, efforts to harness this have been hampered by poor solubility, uptake, bioavailability, and metabolic conversion. Therefore, identification of avenues to improve efficacy is necessary for development of ceramide-based therapies. In this study, we used mutant p53, triple-negative breast cancer (TNBC) cells, a type of breast cancer highly refractory to treatment, and cell-permeable nanoliposomal C6-ceramide in conjunction with the antiestrogen tamoxifen, which has been shown to be an effective modulator of ceramide metabolism. We show for the first time that nanoliposomal tamoxifen enhances nanoliposomal C6-ceramide cytotoxicity in cultured TNBC cells, a response that was accompanied by induction of cell-cycle arrest at G1 and G2, caspase-dependent induction of DNA fragmentation, and enhanced mitochondrial and lysosomal membrane permeability at 18 and 2 hours, respectively. Tamoxifen metabolites were also effective. Only tamoxifen promoted lysosomal membrane permeability. In addition, we show for the first time that tamoxifen inhibits acid ceramidase, as measured in intact cell assays; this effect was irreversible. Together, our findings show that tamoxifen magnifies the antiproliferative effects of C6-ceramide via combined targeting of cell-cycle traverse and lysosomal and mitochondrial integrity. We adduce that C6-ceramide–induced apoptosis is amplified by tamoxifen's impact on lysosomes and perhaps accompanying inhibition of acid ceramidase, which could result in decreased levels of sphingosine 1-phosphate. This drug regimen could serve as a promising therapy for chemoresistant and triple-negative types of breast cancer, and thus represents an indication for tamoxifen, irrespective of estrogen receptor status. Mol Cancer Ther; 11(11); 2352–61. ©2012 AACR.
The Use Of Bottleneck Starvation Avoidance With Queue Predictions In Shop Floor Control

The accurate estimation of lead times and the use of factory-wide information can improve the performance of dynamic shop floor control. This paper presents a dispatching policy that is based on the concept of bottleneck starvation avoidance and relies on frequently updated queue predictions for all workstations. The queue predictions are used to dynamically estimate the lead times required for lots to reach workstations on their routes, particularly the bottleneck workstation. Object-oriented simulation experiments were run for several wafer fab configurations with results showing a consistantly good behavior of the computationally intensive control mechanism presented here.
Alcohol use among college students: an international perspective

Purpose of review The present review of published articles during 2005–2006 on alcohol use among college students in Africa, Asia, Australasia, Europe and South America assesses the prevalence of alcohol use, hazardous drinking and related problems, and reviews the effectiveness of intervention methods and implications for future research. Recent findings Research on alcohol use and related problems in college students is lacking in many regions of the world. We identified 26 papers in peer-reviewed journals, from Australia, Brazil, Ecuador, Egypt, Germany, Hong Kong, Ireland, Lebanon, New Zealand, Nigeria, Sweden, The Netherlands and Turkey. Summary More comprehensive studies with systematic methodologies in the world regions reviewed here are needed to yield representative results on alcohol use and related risk and protective factors in college settings. College students in many countries are at elevated risk for heavy drinking, with serious immediate health risks, such as drink-driving and other substance use; and longer term risks, such as alcohol dependence. The prevalence of hazardous drinking in Australasia, Europe and South America appears similar to that in North America, but is lower in Africa and Asia. Alcohol policies should be reviewed and prevention programmes initiated in light of research evidence, for this high-risk population.
Low fasting plasma glucose level as a predictor of cardiovascular disease and all-cause mortality.

BACKGROUND Although medical textbooks usually classify fasting plasma glucose <70 or 80 mg/dL (<3.89 or 4.44 mmol/L) as abnormal, the prognosis for patients with low fasting plasma glucose is unclear. METHODS AND RESULTS We conducted prospective cohort studies among 40 069 men and women to investigate the association between fasting plasma glucose levels and cardiovascular disease and all-cause mortality. We documented a U-shaped relation between fasting plasma glucose and mortality. In addition to diabetes and impaired fasting glucose levels, low fasting plasma glucose levels were also associated with high mortality. After multivariate adjustment for age, sex, study population, ethnicity, current smoking status, high blood pressure, total cholesterol, body mass index, triglycerides, history of cardiovascular disease and cancer, and a family history of cardiovascular disease, patients with fasting plasma glucose <70 mg/dL (<3.89 mmol/L) had a 3.3-fold increased risk of cardiovascular disease mortality, and patients with fasting plasma glucose 70 to 79 mg/dL (3.89 to 4.43 mmol/L) had a 2.4-fold increased risk compared with the risk in patients with fasting plasma glucose 80 to 109 mg/dL (4.44 to 6.05 mmol/L) (tests for trend P<0.0001). Participants with low fasting plasma glucose levels also had increased risk of all-cause mortality (test for trend P<0.0001). CONCLUSIONS Participants with low fasting plasma glucose levels had a high risk of cardiovascular disease and all-cause mortality.
HPV vaccine knowledge and beliefs among Cambodian American parents and community leaders.

BACKGROUND The cervical cancer incidence rate among Cambodian American women is 15.0 per 100,000, compared to 7.7 per 100,000 among non-Latina white women. HPV infection has been identified as a universal risk factor for cervical cancer. The HPV vaccine was recently approved in the United States for females aged 9-26 years. There is little information about HPV vaccination knowledge and beliefs in Southeast Asian communities. METHODS We conducted 13 key informant interviews with Cambodian community leaders, as well as four focus groups with Cambodian parents (37 participants). Two of the focus groups included fathers and two of the focus groups included mothers. Interview and focus group questions addressed HPV vaccine barriers and facilitators. RESULTS Participants had limited knowledge about HPV infection and the HPV vaccine. Barriers to HPV vaccination included a lack of information about the vaccine, as well as concerns about vaccine safety, effectiveness, and financial costs. The most important facilitators were a health care provider recommendation for vaccination and believing in the importance of disease prevention. DISCUSSION Future cervical cancer control educational programs for Cambodians should promote use of the HPV vaccine for age-eligible individuals. Health care providers who serve Cambodian communities should be encouraged to recommend HPV vaccination.
Centroid-based Text Summarization through Compositionality of Word Embeddings

The textual similarity is a crucial aspect for many extractive text summarization methods. A bag-of-words representation does not allow to grasp the semantic relationships between concepts when comparing strongly related sentences with no words in common. To overcome this issue, in this paper we propose a centroid-based method for text summarization that exploits the compositional capabilities of word embeddings. The evaluations on multi-document and multilingual datasets prove the effectiveness of the continuous vector representation of words compared to the bag-of-words model. Despite its simplicity, our method achieves good performance even in comparison to more complex deep learning models. Our method is unsupervised and it can be adopted in other summarization tasks.
Dual Analysis of the Murine Cytomegalovirus and Host Cell Transcriptomes Reveal New Aspects of the Virus-Host Cell Interface

Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases.
Reference values for vertebral artery flow volume by duplex sonography in young and elderly adults.

BACKGROUND AND PURPOSE Vertebrobasilar ischemia has been attributed to a reduction of net vertebral artery flow volume, the product of mean flow velocity and the cross-sectional area of the vessel. It can be determined by duplex sonography. There are no reference values for vertebral artery flow volume in an age group representative of patients with cerebrovascular disease. METHODS We examined 50 nonvascular neurological patients (age 55.8+/-14.0 years). Flow velocities and vessel diameters were recorded in the intertransverse (V2) segments bilaterally, and the flow volume was calculated according to the following equations: (1) Q1=time-averaged mean velocity times area and (2) Q2=(time-averaged maximum velocity/2)times area. RESULTS Flow velocities and vessel diameters tended to be lower on the right side, resulting in a lower flow volume. Flow volumes (according to Equation 1) were 77.2+/-29.8 mL/min on the right side, 105.3+/-46.4 mL/min on the left side, and 182.0+/-56.0 mL/min net. Side-to-side differences were not significant. Flow volumes calculated with the 2 equations did not differ significantly. An age dependence could not be shown, but vessel diameters and net vertebral artery flow volumes were significantly lower in women than in men. The normal range for net vertebral artery flow volume defined by the 5th to 95th percentiles is between 102.4 and 301.0 mL/min. This wide range is due to the high interindividual variability of the parameters. CONCLUSIONS On the basis of the reference values presented here, the association of decreased vertebral artery flow volume and vertebrobasilar ischemia should be reevaluated. Additional areas for investigation include the quantification of collateral flow in the vertebral arteries in carotid artery occlusive disease and their contribution to overall cerebral blood flow volume.
Molecular analysis of transferrin receptor mRNA expression in acute myeloid leukaemia

Transferrin receptor (TfR, CD71) is an integral membrane glycoprotein that mediates cellular uptake of iron. In most tissues, TfR expression is correlated positively with proliferation and regulated at the post‐transcriptional level. The available data regarding the pattern of TfR gene expression in haematological malignancies are very limited. In the present study, we evaluated TfR gene expression at the molecular level in bone marrow (BM) samples of 44 patients with de novo acute myeloid leukaemia (AML) at diagnosis with BM blasts > 85%. TfR mRNA levels were determined by densitometric analysis of quantitative reverse transcription polymerase chain reaction products corresponding to TfR exons 15–17. Each sample was tested in at least two independent experiments. In 13/44 patients, TfR messages were not detected (this is probably an underestimate as some positive results may be attributed to residual normal erythroid cells present in the samples). In 17/44, TfR mRNA levels were low–intermediate, and were high in the remaining patients (14/44). TfR mRNA positivity was significantly associated with older age. No statistically significant correlations were found either with specific French–American–British (FAB) subtypes or attainment of complete remission, incidence of relapse and survival (after adjusting accordingly for age and FAB subtype). The absence of TfR mRNA transcripts in a significant minority of cases suggests that alternative mechanisms of iron uptake may function in AML blast cells.
Deposited in DRO : 25 January 2016 Version of attached le : Published Version Peer-review status of attached le : Peer-reviewed Citation for published item

Publisher's copyright statement: Reprinted with permission from the American Physical Society: Physical Review D 92, 121901(R) c © (2015) by the American Physical Society. Readers may view, browse, and/or download material for temporary copying purposes only, provided these uses are for noncommercial personal purposes. Except as provided by law, this material may not be further reproduced, distributed, transmitted, modi ed, adapted, performed, displayed, published, or sold in whole or part, without prior written permission from the American Physical Society.
Environmental Pollution from Illegal Waste Disposal and Health Effects: A Review on the “Triangle of Death”

The term “triangle of death” was used for the first time by Senior and Mazza in the journal The Lancet Oncology referring to the eastern area of the Campania Region (Southern Italy) which has one of the worst records of illegal waste dumping practices. In the past decades, many studies have focused on the potential of illegal waste disposal to cause adverse effects on human health in this area. The great heterogeneity in the findings, and the bias in media communication has generated great healthcare doubts, anxieties and alarm. This paper addresses a review of the up-to-date literature on the “triangle of death”, bringing together the available information on the occurrence and severity of health effects related to illegal waste disposal. The Scopus database was searched using the search terms “waste”, “Campania”, “Naples”, “triangle of death” and “human biomonitoring”. Despite the methodological and sampling heterogeneity between the studies, this review examines the evidence from published data concerning cancer incidence, childhood mortality and birth defects, so that the current situation, knowledge gaps and research priorities can be established. The review aims to provide a contribution to the scientific community, and to respond to the concerns of the general population.
Dialysis or not? A comparative survival study of patients over 75 years with chronic kidney disease stage 5.

BACKGROUND The number of elderly patients with chronic kidney disease (CKD) stage 5 is steadily increasing. Evidence is needed to inform decision-making for or against dialysis, especially in those patients with multiple comorbid conditions for whom dialysis may not increase survival. We therefore compared survival of elderly patients with CKD stage 5, managed either with dialysis or conservatively (without dialysis), after the management decision had been made, and explored which of several key variables were independently associated with survival. METHODS A retrospective analysis of the survival of all over 75 years with CKD stage 5 attending dedicated multidisciplinary pre-dialysis care clinics (n=129) was performed. Demographic and comorbidity data were collected on all patients. Survival was defined as the time from estimated GFR<15 ml/min to either death or study endpoint. RESULTS One- and two-year survival rates were 84% and 76% in the dialysis group (n=52) and 68% and 47% in the conservative group (n=77), respectively, with significantly different cumulative survival (log rank 13.6, P<0.001). However, this survival advantage was lost in those patients with high comorbidity scores, especially when the comorbidity included ischaemic heart disease. CONCLUSIONS In CKD stage 5 patients over 75 years, who receive specialist nephrological care early, and who follow a planned management pathway, the survival advantage of dialysis is substantially reduced by comorbidity and ischaemic heart disease in particular. Comorbidity should be a major consideration when advising elderly patients for or against dialysis.
Isogeny classes of abelian varieties over function fields

We study finiteness problems for isogeny classes of abelian varieties over an algebraic function field K in one variable over the field of complex numbers. In particular, we construct explicitly a non‐isotrivial absolutely simple abelian fourfold X over a certain K such that the isogeny class of X×X contains infinitely many mutually non‐isomorphic principally polarized abelian varieties. (Such examples do not exist when the ground field is finitely generated over its prime subfield.)