Miracle-dz/UniFAR-FTUs huggingface dataset:
Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotoxicity

ABSTRACT Anti-HIV-1 envelope glycoprotein (Env) antibodies without broadly neutralizing activity correlated with protection in the RV144 clinical trial, stimulating interest in other protective mechanisms involving antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC). Env epitopes targeted by many antibodies effective at mediating ADCC are poorly exposed on the unliganded Env trimer. Here we investigated the mechanism of exposure of ADCC epitopes on Env and showed that binding of Env and CD4 within the same HIV-1-infected cell effectively exposes these epitopes. Env capacity to transit to the CD4-bound conformation is required for ADCC epitope exposure. Importantly, cell surface CD4 downregulation by Nef and Vpu accessory proteins and Vpu-mediated BST-2 antagonism modulate exposure of ADCC-mediating epitopes and reduce the susceptibility of infected cells to this effector function in vitro. Significantly, Env conformational changes induced by cell surface CD4 are conserved among Env from HIV-1 and HIV-2/SIVmac lineages. Altogether, our observations describe a highly conserved mechanism required to expose ADCC epitopes that might help explain the evolutionary advantage of downregulation of cell surface CD4 by the HIV-1 Vpu and Nef proteins. IMPORTANCE HIV-1 envelope epitopes targeted by many antibodies effective at mediating antibody-dependent cell-mediated cytotoxicity (ADCC) are poorly exposed on the unliganded envelope trimer. Here we investigated the mechanism of exposure of these epitopes and found that envelope interaction with the HIV-1 CD4 receptor is required to expose some of these epitopes. Moreover, our results suggest that HIV-1 CD4 downregulation might help avoid the killing of HIV-1-infected cells by this immune mechanism.
On Explicit / Implicit and Incompressible / Compressible Issues of Immersed Boundary / Continuum Methods

In addition to an overview of the immersed boundary/continuum methods and their finite element formulations, explicit vs. implicit and incompressible vs. compressible issues are discussed. The recent finite element formulations retain the same strategies employed in the original immersed boundary method, namely, the independent Lagrangian solid mesh moves on top of a fixed or prescribed background Eulerian fluid mesh. The added features in recent finite element formulations are the generality of the immersed solid which can occupy a finite volume in the fluid and be impermeable, compressible, and highly deformable. Furthermore, a matrix-free Newton-Krylov iterative solution technique also resolves the time step limitation issues related to stiff spring supports from the boundary and the high elasticity moduli of the immersed solid. This implicit iterative approach enables the application of immersed methods to many engineering problems some of which are documented here for illustrative purposes.
Glial- and Neuronal-Specific Expression of CCL5 mRNA in the Rat Brain

Chemokine (C-C motif) ligand 5 (CCL5) belongs to a group of chemokines that play a role in the peripheral immune system, mostly as chemoattractant molecules, and mediate tactile allodynia. In the central nervous system (CNS), CCL5 and its receptors have multiple functions, including promoting neuroinflammation, insulin signaling, neuromodulator of synaptic activity and neuroprotection against a variety of neurotoxins. Evidence has also suggested that this chemokine may regulate opioid response. The multifunctional profile of CCL5 might correlate with its ability to bind different chemokine receptors, as well as with its unique cellular expression. In this work, we have used fluorescence in situ hybridization combined with immunohistochemistry to examine the expression profile of CCL5 mRNA in the adult rat brain and provide evidence of its cellular localization. We have observed that the highest expression of CCL5 mRNA occurs in all major fiber tracts, including the corpus callosum, anterior commissure, and cerebral peduncle. In these tracts, CCL5 mRNA was localized in oligodendrocytes, astrocytes and microglia. Astrocytic and microglial expression was also evident in several brain areas including the cerebral cortex, caudate/putamen, hippocampus, and thalamus. Furthermore, using a specific neuronal marker, we observed CCL5 mRNA expression in discrete layers of the cortex and hippocampus. Interestingly, in the midbrain, CCL5 mRNA co-localized with tyrosine hydroxylase (TH) positive cells of the ventral tegmental area, suggesting that CCL5 might be expressed by a subset of dopaminergic neurons of the mesolimbic system. The expression of CCL5 mRNA and protein, together with its receptors, in selected brain cell populations proposes that this chemokine could be involved in neuronal/glial communication.
A versatile vector for mycobacterial protein production with a functional minimized acetamidase regulon

Recombinant protein expression is a prerequisite for diverse investigations of proteins at the molecular level. For targets from Mycobacterium tuberculosis it is favorable to use M. smegmatis as an expression host, a species from the same genus. In the respective shuttle vectors, target gene expression is controlled by the complex tetra‐cistronic acetamidase regulon. As a result, the size of those vectors is large, rendering them of limited use, especially when the target proteins are expressed from multi‐cistronic operons. Therefore, in the current work we present a versatile new expression vector in which the acetamidase regulon has been minimized by deleting the two genes amiD and amiS. We assessed the functional properties of the resulting vector pMyCA and compared it with those of the existing vector pMyNT that contains the full‐length acetamidase regulon. We analyzed the growth features and protein expression patterns of M. smegmatis cultures transformed with both vectors. In addition, we created mCherry expression constructs to spectroscopically monitor the expression properties of both vectors. Our experiments showed that the minimized vector exhibited several advantages over the pMyNT vector. First, the overall yield of expressed protein is higher due to the higher yield of bacterial mass. Second, the heterologous expression was regulated more tightly, offering an expression tool for diverse target proteins. Third, it is suitable for large multi‐protein complexes that are expressed from multi‐cistronic operons. Additionally, our results propose a new understanding of the regulation mechanism of the acetamidase regulon with the potential to construct more optimized vectors in the future.
Recombinant superoxide dismutase from a hyperthermophilic archaeon, Pyrobaculum aerophilum

Superoxide dismutase (SOD) from the hyperthermophilic archaeon Pyrobaculum aerophilum (a facultative aerobe) has been cloned and expressed in a mesophilic host (Escherichia coli) as a soluble tetrameric apoprotein. The purified apoprotein can be reconstituted with either Mn or Fe by heating the protein with the appropriate metal salt at an elevated temperature (95 °C). Both Mn- and Fe-reconstituted P. aerophilum SOD exhibit superoxide dismutase activity, with the Mn-containing enzyme having the higher activity. P. aerophilum SOD is extremely thermostable and the reconstitution with Mn(II) can be performed in an autoclave (122 °C, 18 psi). The Mn(III) optical absorption spectrum of Mn-reconstituted P. aerophilum SOD is distinct from that of most other MnSODs and is unchanged upon addition of NaN3. The optical absorption spectrum of Fe-reconstituted P. aerophilum SOD is typical of Fe-substituted MnSODs and authentic Fe- SOD and exhibits a pH-dependent transition with an effective pKa value higher than that found for Fe-substituted MnSOD from either E. coli or Thermus spp. Amino acid sequence analysis shows that the P. aerophilum SOD is closely related to SODs from other hyperthermophilic archaea (Aeropyrum pernix and Sulfolobus spp.), forming a family of enzymes distinct from the hyperthermophilic bacterial SOD from Aquifex pyrophilus and from mesophilic SODs.
CLS to Higher Education Administrator: The Right Place – Right Time

OBJECTIVES: To document the career paths of women clinical laboratory scientists who have transitioned from employment in a full service clinical laboratory to the higher education arena and who have administrative positions at the dean's level, including assistant and associate dean positions. METHODS: A multi-site case study design was selected for this qualitative research involving a purposive sample of eight research participants. Data collection was guided by ten open-ended questions in seven face-to-face and one telephone semi-formal interviews. SETTING AND PARTICIPANTS: The purposive sample included women who held a current higher education administrative position at the dean's level, including associate and assistant dean positions, in a university setting. These women also possessed a background in clinical laboratory science. The participants were located in eight higher education institutions in Nebraska, Illinois, Ohio, Tennessee, Missouri, and Texas. MAIN OUTCOMES MEASURES: Experience as a clinical laboratory scientist, experience as faculty, experience as a higher education administrator, description of career path. RESULTS: The participants of this qualitative study selected clinical laboratory science as their area of formal education through various means. Through no intentional action on their part, all of these women became faculty members in clinical laboratory education programs. By exhibiting the necessary knowledge and skills, these faculty members were selected to move into higher education administrator positions. The participants indicated their career paths were determined by “being in the right place at the right time” versus pre-determined career goals. CONCLUSION: Participants in this study indicated having a background in clinical laboratory science enhanced their ability to obtain a position as a higher education administrator. ABBREVIATIONS: CLS=Clinical laboratory science; CLS/MT=Clinical laboratory scientist/medical technologist; CLT/MLT=Clinical laboratory technician/medical laboratory technician; CLE=Clinical laboratory education.
EGF targeted fluorescence molecular tomography as a predictor of PDT outcomes in pancreas cancer models

Verteporfin photodynamic therapy (PDT) is a promising adjuvant therapy for pancreas cancer and investigations for its use are currently underway in both orthotopic xenograft mouse models and in human clinical trials. The mouse models have been studied extensively using magnetic resonance (MR) imaging as a measure of surrogate response to verteporfin PDT and it was found that tumor lines with different levels of aggression respond with varying levels to PDT. MR imaging was successful in determining the necrotic volume caused by PDT but there was difficultly in distinguishing inflamed tissues and regions of surviving tumor. In order to understand the molecular changes within the tumor immediately post-PDT we propose the implementation of MR-guided fluorescence molecular tomography (FMT) in conjunction with an exogenously administered fluorescently labeled epidermal growth factor (EGF-IRDye800CW, LI-COR Biosciences). We have previously shown that MR-guided FMT is feasible in the mouse abdomen when multiple regions of fluorescence are considered from contributing internal organs. In this case the highly aggressive AsPC-1 (+EGFR) orthotopic tumor was implanted in SCID mice, interstitial verteporfin PDT (1mg/kg, 20J/cm) was performed when the tumor reached ~60mm3 and both tumor volume and EGF binding were followed with MR-guided FMT.
Experimental Tests of Local Lorentz Invariance

Lorentz invariance, fundamental to Relativity and the Standard Model, has been thoroughly investigated both theoretically and experimentally in the past 15 years. This investigation, motivated in large by attempts to unify gravity with the Standard Model through quantum gravity, has led to strict constraints on the nature and size of a violation. A historical perspective of Lorentz’s work, a brief discussion of the theoretical framework, and a discussion of high-precision tests and their results are presented.
Identi fi cation of the PTPN 22 functional variant R 620 W as susceptibility genetic factor for giant cell arteritis

Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis A Serrano, A Márquez, S L Mackie, F D Carmona, R Solans, J A Miranda-Filloy, J Hernández-Rodríguez, M C Cid, S Castañeda, IC Morado, J Narváez, R Blanco, B Sopeña, M J García-Villanueva, J Monfort, N Ortego-Centeno, A Unzurrunzaga, B Marí-Alfonso, J Sánchez-Martín, E de Miguel, C Magro, E Raya, N Braun, J Latus, O Molberg, B A Lie, F Moosig, T Witte, A W Morgan, M A González-Gay, J Martín, UK GCA Consortium Spanish GCA Consortium
Effect of concurrent training on left ventricular contractile function in patients with coronary artery disease

Field: Physical Activity has an accepted role in cardiac rehabilitation, which is due to more for its positive effects on blood stream of cardiac muscle in coronary artery patients. The mechanism of this improvement is questionable and improvement of medium vascular system and contractile function of cardiac’s muscle have suggested as possible adjustments. The aim of this study is the study of combinational exercise on left ventricular contractile function in the patients with coronary artery disease. Methodology: Twenty-four (24) coronary artery patients were divided into two experimental groups (average age: 60+/6 old, average weight: 74+/kg, and average index of body mass: 26+/-4) as randomly (n=12) and control (n=12) groups. Experimental group participated in combinational exercise for 3 months, three times in a week for 60-80 minutes and the maximum heart beat was seen in 70% to 85% and 40% to 60% participated in a maximum repetition. The studied variables were evaluated primarily and at the end of plan with Impedance Cardiography method. Findings: The exercises caused meaningful decreasing of heart beat and rest blood pressure of patients. Acceleration index of blood output (ACI) increased from 0.49+/0.14 to 0.78+/-0.24 in square seconds (P<0.05). Velocity Index of blood output (VI) increased from 36+/-9 to 47+/-8 milli seconds (P<0.05). Left Cardiac Work Index (LCWI) increased from 3+/-1 to 4+/-1 kgm/square meters (P<0.05). Pre Ejection Period of blood (PEP) decreased from 91+/12 to 68+/-19 milli seconds. The Systolic Time Ratio (STR) decreased from 28+/5 to 21+/-6 (P<0.05). Left Ventricular Ejection Time (LVET) had no meaningful change. Conclusion: We concluded that the combinational exercise may cause the improvement of cardiac muscle contractile function in patients with coronary artery disease.
Wave height prediction at the Caspian Sea using a data-driven model and ensemble-based data assimilation methods

There are successful experiences with the application of ANN and ensemble-based data assimilation methods in the field of flood forecasting and estuary flow. In the present work, the combination of dynamic Artificial Neural Network and Ensemble Kalman Filter (EnKF) is applied on wind-wave data. ANN is used for the time propagation mechanism that governs the time evolution of the system state. The system state consists of the significant wave height that is affected by wind speed and wind direction. The relevant inputs are selected by analysing the Average Mutual Information. By help of the observations, the EnKF will correct the output of the ANN to find the best estimate of the wave height. A combination of ANN with EnKF acts as an output correction scheme. To deal with the time-delayed states, the extended state vector is taken and the dynamic equation of the extended state vector is used in EnKF. Application of the proposed scheme is examined by using five-month hourly buoy measurement at the Caspian Sea and several model runs with different assimilation–forecast cycles.The coefficient of performance and root mean square error are used to access performance of the method.
Evaluation of unsupervised indoor localisation algorithm using real-environment data

Localisation is becoming increasingly important. It can be used in navigation, social media, and various economic activities. Outdoor localisation is well established through the usage of GPS. However, indoor localisation is still an active research area. Indoor localisation has become increasingly important over the years as more people tend to spend time in indoors. It is possible to train a location's Wi-Fi data based on its density distribution. The trained location could further be used for recognition in future visits. This project aims to implement and modify DCCLA (Density-based Clustering Combined Localisation Algorithm) to allow indoor localisation in a public environment.
Disability and patient’s appraisal of general health contribute to depressed mood in rheumatoid arthritis in a large clinical study in Japan

The aim of this study was to evaluate the factors responsible for depressed mood in rheumatoid arthritis (RA). Clinical and laboratory measures were collected from 4558 RA patients enrolled in a large clinical cohort study for RA conducted at the Institute of Rheumatology, Tokyo Women’s Medical University (IORRA study). A two-question depressed screening included in the U.S. Preventive Services Task Force recommendation were utilized to identify “depressed patients. ” A total of 1875 (41.1%) were identified as “depressed patients” who presented with symptoms suggestive of depression. Patient’s Visual Analog Scale (VAS) for general health (43.3 mm vs 24.6 mm, P < 0.0001) and pain (40.9 mm vs 23.8 mm, P < 0.0001) and the disability index scores measured by the Health Association Questionnaire (HAQ) (0.986 vs 0.574, P < 0.0001) were significantly higher in depressed patients than in nondepressed patients. The presence of three or more comorbidities (odds ratio [OR] 2.157, P < 0.0001), infection (OR 1.754, P < 0.0001), and joint surgery (OR 1.878, P < 0.0001) were significantly correlated with depressed mood in RA. The results of the Generalized Linear Model analysis showed that HAQ disability index (P < 0.0001) and patient’s VAS for general health (P < 0.0001) were also strongly and significantly associated to the response variable “probability of depressed patients. ’ Patient appraisal of poor general health and greater disability were associated with depressed mood in RA.
Distribution of Endothelial Cell Protein C/Activated Protein C Receptor (EPCR) During Mouse Embryo Development

Summary The endothelial cell protein C receptor (EPCR) augments protein C activation by the thrombomodulin•thrombin complex. Deletion of the EPCR gene in mice has been reported to lead to embryonic lethality before embryonic day 10 (E10.0). To identify potential mechanisms responsible for this lethality, we performed an immunohistological analysis of EPCR distribution during mouse embryogenesis. EPCR was detected in the trophoblast giant cells at the feto-maternal boundary from E7.5 and at later time points in the trophoblasts of the placenta, suggesting a role in the haemostatic regulation of the maternal blood that irrigates these surfaces. In the embryo, EPCR was weakly detected in aortic endothelial cells from E13.5. Thereafter, EPCR levels increased in certain large blood vessel endothelial cells suggesting that the specificity of EPCR to large vessels is conferred in utero. However, not until postnatal day 7 did the intensity and distribution of EPCR staining mimic that observed in adult mice. Abbreviations: APC – activated protein C, AP – alkaline phosphatase, EC – endothelial cell, EPCR – endothelial cell protein C/activated protein C receptor, FITC – fluorescein isothiocyanate, HRP – horseradish peroxidase, PBS – phosphate-buffered saline, TM – thrombomodulin, WT – wild–type
Role of Hox PG2 genes in Nile tilapia pharyngeal arch specification: implications for gnathostome pharyngeal arch evolution

SUMMARY Phylogenetic reconstructions suggest that the ancestral osteichthyan Hox paralog group 2 gene complement was composed of two genes, Hoxa2 and b2, both of which have been retained in tetrapods, but only one of which functions as a selector gene of second pharyngeal arch identity (PA2). Genome duplication at the inception of the teleosts likely generated four Hox PG2 genes, only two of which, hoxa2b and b2a, have been preserved in zebrafish, where they serve as functionally redundant PA2 selector genes. Evidence from our laboratory has shown that other telelosts, specifically striped bass and Nile tilapia, harbor three transcribed Hox PG2 genes, hoxa2a, a2b, and b2a, with unspecified function(s). We have focused on characterizing the function of the three Nile tilapia Hox PG2 genes as a model to examine the effects of postgenome duplication gene loss on the evolution of developmental gene function. We studied Hox PG2 gene function in tilapia by examining the effects of independent morpholino oligonucleotide (MO)‐induced knockdowns on pharyngeal arch morphology and Hox gene expression patterns. Morphological defects resulting from independent MO‐induced knockdowns of tilapia hoxa2a, a2b, and b2a included the expected PA2 to PA1 homeotic transformations previously observed in tetrapods and zebrafish, as well as concordant and unexpected morphological changes in posterior arch‐derived cartilages. Of particular interest, was the observation of a MO‐induced supernumerary arch between PA6 and PA7, which occurred concomitantly with other MO‐induced pharyngeal arch defects. Beyond these previously unreported morphant‐induced transformations, a comparison of Hox PG2 gene expression patterns in tilapia Hox PG2 morphants were indicative of arch‐specific auto‐ and cross‐regulatory activities as well as a Hox paralog group 2 interdependent regulatory network for control of pharyngeal arch specification.
“Nature, green in leaf and stem”. Research on plants with medicinal properties in Suriname

The widely held layman’s perception of nature as a collection of animals operating against a static green background of plants is a serious misunderstanding of the complexity and dynamics of the plant biodiversity. Plants fulfill all functions that superficially only seem reserved for animals including movement, communication, and defense. For the latter purposes, plants have developed intricate and highly sophisticated chemical warning signals and defense systems to alarm friends and ward off foes. Many of these plant substances possess meaningful pharmacological properties, and some were found useful against human diseases. This paper briefly describes several aspects of plant communication and defense; gives a few examples of plant-derived therapeutics; and focuses on the potential contribution of Suriname (South America) to this scientific area. Correspondence to: Dennis RA Mans, Department of Pharmacology, Faculty of Medical Sciences, Anton de Kom University of Suriname, USA, Tel: 597 441071; E-mail: dennis_mans@yahoo.com