Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of a Myosin VII-Talin Complex*

Myosin VII (M7) plays a role in adhesion in both Dictyostelium and mammalian cells where it is a component of a complex of proteins that serve to link membrane receptors to the underlying actin cytoskeleton. The nature of this complex is not fully known, prompting a search for M7-binding proteins. Co-immunoprecipitation experiments reveal that Dictyostelium M7 (DdM7) interacts with talinA, an actin-binding protein with a known role in cell-substrate adhesion. No additional proteins are observed in the immunoprecipitate, indicating that the interaction is direct. The N-terminal region of the DdM7 tail that lies between the region of predicted coil and the first MyTH4 domain is found to harbor the talinA binding site. Localization experiments reveal that talinA does not serve as a membrane receptor for DdM7 and vice versa. These findings reveal that talinA is a major DdM7 binding partner and suggest that their interaction induces a conformational change in each that, in combination with membrane receptor binding, promotes the assembly of a high avidity receptor complex essential for adhesion of the cell to substrata.
Carotid artery plaque morphology and composition in relation to incident cardiovascular events: the Multi-Ethnic Study of Atherosclerosis (MESA).

PURPOSE To determine if carotid plaque morphology and composition with magnetic resonance (MR) imaging can be used to identify asymptomatic subjects at risk for cardiovascular events. MATERIALS AND METHODS Institutional review boards at each site approved the study, and all sites were Health Insurance Portability and Accountability Act (HIPAA) compliant. A total of 946 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) were evaluated with MR imaging and ultrasonography (US). MR imaging was used to define carotid plaque composition and remodeling index (wall area divided by the sum of wall area and lumen area), while US was used to assess carotid wall thickness. Incident cardiovascular events, including myocardial infarction, resuscitated cardiac arrest, angina, stroke, and death, were ascertained for an average of 5.5 years. Multivariable Cox proportional hazards models, C statistics, and net reclassification improvement (NRI) for event prediction were determined. RESULTS Cardiovascular events occurred in 59 (6%) of participants. Carotid IMT as well as MR imaging remodeling index, lipid core, and calcium in the internal carotid artery were significant predictors of events in univariate analysis (P < .001 for all). For traditional risk factors, the C statistic for event prediction was 0.696. For MR imaging remodeling index and lipid core, the C statistic was 0.734 and the NRI was 7.4% and 15.8% for participants with and those without cardiovascular events, respectively (P = .02). The NRI for US IMT in addition to traditional risk factors was not significant. CONCLUSION The identification of vulnerable plaque characteristics with MR imaging aids in cardiovascular disease prediction and improves the reclassification of baseline cardiovascular risk.
Platelet‐Derived Growth Factor‐D Overexpression Contributes to Epithelial‐Mesenchymal Transition of PC3 Prostate Cancer Cells

The majority of human malignancies are believed to have epithelial origin, and the progression of cancer is often associated with a transient process named epithelial‐mesenchymal transition (EMT). EMT is characterized by the loss of epithelial markers and the gain of mesenchymal markers that are typical of “cancer stem‐like cells,” which results in increased cell invasion and metastasis in vivo. Therefore, it is important to uncover the mechanistic role of factors that may induce EMT in cancer progression. Studies have shown that platelet‐derived growth factor (PDGF) signaling contributes to EMT, and more recently, PDGF‐D has been shown to regulate cancer cell invasion and angiogenesis. However, the mechanism by which PDGF‐D promotes invasion and metastases and whether it is due to the acquisition of EMT phenotype remain elusive. For this study, we established stably transfected PC3 cells expressing high levels of PDGF‐D, which resulted in the significant induction of EMT as shown by changes in cellular morphology concomitant with the loss of E‐cadherin and zonula occludens‐1 and gain of vimentin. We also found activation of mammalian target of rapamycin and nuclear factor‐κB, as well as Bcl‐2 overexpression, in PDGF‐D PC3 cells, which was associated with enhanced adhesive and invasive behaviors. More importantly, PDGF‐D‐overexpressing PC3 cells showed tumor growth in SCID mice much more rapidly than PC3 cells. These results provided a novel mechanism by which PDGF‐D promotes EMT, which in turn increases tumor growth, and these results further suggest that PDGF‐D could be a novel therapeutic target for the prevention and/or treatment of prostate cancer.
Sexually transmitted infections: controversies and conundrums in screening, treatment and stigma.

DOI:10.1097/QCO.0000000000000035 The five review topics in this issue highlight some of the key controversies in sexually transmitted infections (STIs), and their control. The authors are from all corners of the world and work in different healthcare systems, but all have an awareness of the internationality of STIs, which do not conform to national boundaries. A problem in one country can rapidly spread to other continents, requiring a world view of STI treatment and control, and international collaboration and support. There are some major areas of concern: in men who have sex with men (MSM), there is a resurgent syphilis epidemic, hepatitis C in HIV-positive men has an annual incidence of transmission of 2–4% [1], and there is no decrease in HIV incidence in MSM; gonorrhoea has increased globally by 21% over 3 years [2] and multidrug, extensively drug-resistant and potentially untreatable gonorrhoea is a reality; and herpes continues to be a major problem. Hofstetter et al. (pp. 75–83) refer to a major new study showing there is a higher rate of herpes simplex virus (HSV)-1 than HSV-2 primary infection with most cases being genital rather than orolabial disease [3]. Mycoplasma genitalium, as the new kid on the block, is present in about 2% of women aged below 30 years in developed countries (Horner et al.; pp. 68–74), and the majority of clinicians and scientists working in theSTI fieldhave no awareness of the recentworrying data on resistance and treatment failures. The implications of bowel inflammation secondary to infections transmitted sexually, some of which do not come under the banner ‘STIs’, is a new issue. Most of the world continues to remain in recession, and with economic downturns come inevitable pressures on healthcare. There is evidence from many counties that spending on health cannot continue at the same rate, and as demands increase, we need to consider other approaches. A public health approach of STI prevention rather than treatment is one such consideration. Fairley et al. (pp. 56–61) consider more frequent screening for syphilis, HIV and hepatitis C as a way of driving down new infections and, if a reproductive rate less than 1 is achieved, the potential for them becoming functionally eliminated. They highlight
The Tat-dependent protein translocation pathway

Abstract The twin-arginine translocation (Tat) pathway is found in bacteria, archaea, and plant chloroplasts, where it is dedicated to the transmembrane transport of fully folded proteins. These proteins contain N-terminal signal peptides with a specific Tat-system binding motif that is recognized by the transport machinery. In contrast to other protein transport systems, the Tat system consists of multiple copies of only two or three usually small (∼8–30 kDa) membrane proteins that oligomerize to two large complexes that transiently interact during translocation. Only one of these complexes includes a polytopic membrane protein, TatC. The other complex consists of TatA. Tat systems of plants, proteobacteria, and several other phyla contain a third component, TatB. TatB is evolutionarily and structurally related to TatA and usually forms tight complexes with TatC. Minimal two-component Tat systems lacking TatB are found in many bacterial and archaeal phyla. They consist of a ‘bifunctional’ TatA that also covers TatB functionalities, and a TatC. Recent insights into the structure and interactions of the Tat proteins have various important implications.
[Bleeding after cardiac surgery: risk factors, frequency, and outcomes].

UNLABELLED According to the data from different cardiac surgery centers, the incidence of urgent repetitive resternotomy for bleeding after cardiac on-pump operations varies from 2 to 5%. The aim of the study was to determinate the risk factors influencing resternotomy after cardiac surgery, features of early postoperative period, and outcomes. MATERIAL AND METHODS Altogether, 37 consecutive patients undergoing urgent resternotomy due to bleeding early after cardiac surgery were analyzed retrospectively. Urgent resternotomies made up 4.3% of all cardiac on-pump surgeries performed on 856 patients at the Clinic of Cardiac Surgery of Kaunas University of Medicine Hospital during 2004. The mean age of patients was 64.9+/-12.9 years; 29.7% of patients were women and 70.3% were men. RESULTS During analysis of preoperative clinical data factors that could influence coagulation status were determined. Twenty patients (54.1%) had moderate hypertension, three patients (8.1%) had severe insulin-dependent diabetes mellitus, and five patients (13.5%) had chronic renal insufficiency treated with dialysis. Assessing other risk factors it was observed that many patients were on peroral anticoagulation therapy before surgery. The most frequently administered drugs preoperatively were aspirin (16 cases, 43.2%) and direct-acting anticoagulants (17 cases, 45.9%). CONCLUSIONS The use of antiaggregants and anticoagulants before surgery increases the incidence of resternotomies in the early postoperative period. Postoperative infections that require more expensive treatment with antibiotics are detected much more frequently in patients after resternotomies comparing to the remaining postoperative cardiac patients (15/37 and 69/819, respectively). However, longer hospitalization length (15.8 and 58.0 days, respectively) and higher mortality rate (4.5 and 10.8%, respectively) were observed in patients after resternotomy.
IgE elevation and IgE anti‐malarial antibodies in Plasmodium falciparum malaria; association of high IgE levels with cerebral malaria

In the course of studying immunoregulation in human Plasmodium falciparum malaria we have investigated IgE levels and IgE anti‐plasmodial antibodies in children and adults from areas of high malaria endemicity in both Africa and Asia. On average, 85% of all donors had significantly elevated levels of total IgE. A fraction of the IgE had anti‐plasmodial activity as revealed by ELISA with lysates of infected erythrocytes as antigen. Using synthetic peptides representing antigenic regions of two major plasmodial blood stage antigens, IgE antibody concentrations ranged from 5 to 15 ng/ml serum for each of the peptides. On average, the concentrations of the corresponding IgG antibodies were x500‐I000 higher. Immunoblotting of parasite lysates showed that most donors had IgE antibodies against one or several of a restricted number of plasmodial polypeptides, with antibodies against an antigen of mol. wt 45 kD already being present in all donors at an early age. Donors having IgE antibodies to particular antigens also frequently had corresponding IgG4 antibodies, reflecting underlying IL‐4‐dependent cellular mechanisms controlling formation of these isotypes. As infection with other parasites such as helminths is known lo induce IgE elevation, the results do not prove that plasmodial infections were the primary cause of IgE induction. However, the importance of plasmodial infection for IgE elevation was supported by the finding of significantly higher levels of IgE. , but not of IgG, in children with cerebral malaria compared with patients with uncomplicated disease.
Evolved developmental homeostasis disturbed in LB1 from Flores, Indonesia, denotes Down syndrome and not diagnostic traits of the invalid species Homo floresiensis

Significance The population that has become known as Homo floresiensis has been described as “the most extreme human ever discovered. ” Specimen LB1 from Liang Bua Cave is unusual, but craniofacial and postcranial characteristics originally said to be diagnostic of the new species are not evident in the other more fragmentary skeletons in the sample that resemble other recent small-bodied human populations in the region (including the Andaman Islands, Palau, and Flores itself). Here we demonstrate that the facial asymmetry, small endocranial volume, brachycephaly, disproportionately short femora, flat feet, and numerous other characteristics of LB1 are highly diagnostic of Down syndrome, one of the most commonly occurring developmental disorders in humans and also documented in related hominoids such as chimpanzees and orangutans. Human skeletons from Liang Bua Cave, Flores, Indonesia, are coeval with only Homo sapiens populations worldwide and no other previously known hominins. We report here for the first time to our knowledge the occipitofrontal circumference of specimen LB1. This datum makes it possible to link the 430-mL endocranial volume of LB1 reported by us previously, later confirmed independently by other investigators, not only with other human skeletal samples past and present but also with a large body of clinical data routinely collected on patients with developmental disorders. Our analyses show that the brain size of LB1 is in the range predicted for an individual with Down syndrome (DS) in a normal small-bodied population from the geographic region that includes Flores. Among additional diagnostic signs of DS and other skeletal dysplasiae are abnormally short femora combined with disproportionate flat feet. Liang Bua Cave femora, known only for LB1, match interlimb proportions for DS. Predictions based on corrected LB1 femur lengths show a stature normal for other H. sapiens populations in the region.
A comparison of cerebral oxygenation as measured by the NIRO 300 and the INVOS 5100 Near‐Infrared Spectrophotometers

In this study cerebral oxygenation was measured using the NIRO 300 and the INVOS 5100 spectrophotometers in 10 healthy adult volunteers, exposed to varying degrees of hyperoxia and hypoxia. The results showed similar baseline values for tissue oxygenation index and regional cerebral oxygen saturation with mean (SD) values being 64.9% (5.1) and 62.3% (6.0), respectively. The overall bias was –2.1%, with the INVOS 5100 under‐reading cerebral oxygenation compared to the NIRO 300, with limits of agreement of ±14.7%. Both monitors demonstrated similar changes in response to hyperoxia and hypocapnia (coefficient of variance for FIo2 0.45 = 10.0%, FIo2 1.0 = 10.1%, hypocapnia = 14.5%). The reasons for the bias and variability may relate to differences in the methodological approaches of the two monitors. The correlation between the monitors in response to changes in cerebral oxygenation implies that they may be useful as trend monitors in clinical practice.
Gastrointestinal phase of Listeria monocytogenes infection

For many years the Gram-positive facultatively intracellular food-borne pathogen Listeria monocytogenes has been used as a model organism for the study of intracellular parasitism. Whilst the basic mechanisms of cellular pathogenesis have been elucidated by a series of elegant studies, recent research has begun to focus upon the gastrointestinal (GI) phase of L. monocytogenes infection. Epidemiological studies of outbreaks of human disease now demonstrate that the pathogen can cause gastroenteritis in the absence of invasive disease and associated mortality. Furthermore, the pathogen has the ability to colonize the gallbladder in infected mice and this may function as a significant focus of infection during pathogenesis. The ability of the pathogen to survive within the various microenvironments of the GI tract is essential for the causation of food-borne infection. Survival of the pathogen within gastric acid requires the glutamate decarboxylase (GAD) system. In addition, the carnitine uptake system, OpuC is essential for adaptation within the murine GI tract and subsequent invasive disease. Survival of bile salts both in vitro and in vivo requires a number of mechanisms including bile salt hydrolase (Bsh) and the recently described bile exclusion system, BilE (previously OpuB). Finally a number of these systems (including Bsh, OpuC and BilE) are regulated by both the alternative stress sigma factor, Sigma B and by the regulator of virulence gene expression, PrfA.
Identification and Characterization of Gemin7, a Novel Component of the Survival of Motor Neuron Complex*

The survival of motor neurons (SMN) protein is the product of the gene mutated or deleted in the neurodegenerative disease, spinal muscular atrophy. SMN is part of a large macromolecular complex that also contains Gemin2, Gemin3, Gemin4, Gemin5, and Gemin6. The SMN complex functions in the assembly of spliceosomal small nuclear ribonucleoproteins and probably other ribonucleoprotein particles. We have identified a novel protein component of the SMN complex termed Gemin7 using native purified SMN complexes and peptide sequencing by mass spectrometry. Coimmunoprecipitation and immunolocalization experiments demonstrate that Gemin7 is a component of the SMN complex and colocalizes with SMN in the cytoplasm and in gems. Binding experiments show that Gemin7 interacts directly with SMN and Gemin6 and mediates the association of Gemin6 with the SMN complex. The amino acid sequence of Gemin7 does not contain any recognizable motifs with the exception of several arginine and glycine repeats that are necessary for its interaction with SMN. Moreover, Gemin7 interacts with several Sm proteins of spliceosomal small nuclear ribonucleoproteins, in particular, with SmE. With the identification of Gemin7, the inventory of the core components of the SMN complex appears essentially complete.
Mechanisms of antifolate resistance and methotrexate efficacy in leukemia cells

Antifolates are the first class of antimetabolites introduced to clinic about 6 decades ago. Now, after several years of administration of antifolates against malignancies and particularly leukemia, we are still trying to achieve a full understanding of the mechanisms of action and resistance to these agents. The present article covers different factors able to influence efficacy of antifolates on leukemic cells, the known mechanisms of resistance to methotrexate (MTX) and strategies to overcome these mechanisms. The dominant factors that are contributed to tolerance to cytocidal effects of MTX including pharmacokinetic factors, impaired transmembrane uptake as the most frequent rote of provoking resistance to MTX, augmented drug efflux, impaired intracellular polyglutamation as a determining process of drug efficacy, alterations in expression or activity of target enzymes and increased intracellular folate pools; and finally role of 7-hydroxymethotrexate on response or resistance to MTX will be discussed in more detail. Finally, strategies to overcome resistance to antifolates are discussed.
Comparative study of learning algorithms for recognition by hand geometry

This paper presents an approach for personal recognition based on hand geometry applying different classification and training methods to measure the results. The features extraction process prioritizes user comfort during capture and produces segmentation of hands and fingers with high precision. For classification, Bayesian networks and support vector machines methods were applied in three different implementations. Tests using cross-validation and random subsampling techniques were performed. The experiments demonstrated competitive results when compared to other state-of-the-art methods, especially for classification using cross-validation applied to BayesNet and SMO classifiers, both with an accuracy of 99.85%.
Star Cluster Formation and Evolution in Nearby Starburst Galaxies : II . 1 2003

We use the ages, masses and metallicities of the rich young star cluster systems in the nearby starburst galaxies NGC 3310 and NGC 6745 to derive their cluster formation histories and subsequent evolution. We further expand our analysis of the systematic uncertainties involved in the use of broad-band observations to derive these parameters (Paper I) by examining the effects of a priori assumptions on the individual cluster metallicities. The age (and metallicity) distributions of both the clusters in the circumnuclear ring in NGC 3310 and of those outside the ring are statistically indistinguishable, but there is a clear and significant excess of higher-mass clusters in the ring compared to the non-ring cluster sample; it is likely that the physical conditions in the starburst ring may be conducive for the formation of higher-mass star clusters, on average, than in the relatively more quiescent environment of the main galactic disc. For the NGC 6745 cluster system we derive a median age of ∼ 10 Myr. NGC 6745 contains a significant population of high-mass “super star clusters”, with masses in the range 6.5 . log(Mcl/M ) . 8.0. This detection supports the scenario that such objects form preferentially in the extreme environments of interacting galaxies. The age of the cluster populations in both NGC 3310 and NGC 6745 is significantly lower than their respective characteristic cluster disruption time-scales, respectively log(t 4 /yr) = 8.05 and 7.75, for 10M clusters. This allows us to obtain an independent estimate of the initial cluster mass function slope, α = 2.04(±0.23)+0.13 −0.43 for NGC 3310, and 1.96(±0.15)± 0.19 for NGC 6745, respectively, for masses Mcl & 10M and Mcl & 4 × 10M . These mass function slopes are consistent with those of other young star cluster systems in interacting and starburst galaxies.
CBR: Fuzzified case retrieval approach for facial expression recognition

We present a new scheme for the recognition of facial expressions from a set of facial features using fuzzy enhanced Case-based Reasoning (CBR). Facial expression recognition has become the cornerstone of human-computer interaction (HCI) systems. It has wide range applications information systems and e-commerce such as intelligent desktops and intelligent web agents. Our system is the integration of two fundamental paradigms of AI, i.e., Fuzzy logic and Case Based Reasoning. Fuzzy logic is embedded into our CBR system for improved case retrieval. A dual, fuzzy similarity determination module is the core of our system and works within the Case-based Reasoning system. The advantages from Fuzzy Rule Based Systems (FRBS) like linguistic modeling and fault tolerance when combined with the reasoning capability of CBR greatly improved the sophistication and utility of our system. A reinforcing combination of two approaches might lead to exciting applications that are yet to be envisaged.
Enantiomeric-Dependent Phytotoxic and Antimicrobial Activity of (±)-Catechin. A Rhizosecreted Racemic Mixture from Spotted Knapweed1

In this communication, we unravel part of the mystery surrounding the allelopathic capability of the noxious weed spotted knapweed ( Centaurea maculosa ). We have found that (−)-catechin is a root-secreted phytotoxin that undoubtedly contributes to spotted knapweed's invasive behavior in the