Miracle-dz/UniFAR-FTUs huggingface dataset:
Membrane Binding of the Rous Sarcoma Virus Gag Protein Is Cooperative and Dependent on the Spacer Peptide Assembly Domain

ABSTRACT The principles underlying membrane binding and assembly of retroviral Gag proteins into a lattice are understood. However, little is known about how these processes are related. Using purified Rous sarcoma virus Gag and Gag truncations, we studied the interrelation of Gag-Gag interaction and Gag-membrane interaction. Both by liposome binding and by surface plasmon resonance on a supported bilayer, Gag bound to membranes much more tightly than did matrix (MA), the isolated membrane binding domain. In principle, this difference could be explained either by protein-protein interactions leading to cooperativity in membrane binding or by the simultaneous interaction of the N-terminal MA and the C-terminal nucleocapsid (NC) of Gag with the bilayer, since both are highly basic. However, we found that NC was not required for strong membrane binding. Instead, the spacer peptide assembly domain (SPA), a putative 24-residue helical sequence comprising the 12-residue SP segment of Gag and overlapping the capsid (CA) C terminus and the NC N terminus, was required. SPA is known to be critical for proper assembly of the immature Gag lattice. A single amino acid mutation in SPA that abrogates assembly in vitro dramatically reduced binding of Gag to liposomes. In vivo, plasma membrane localization was dependent on SPA. Disulfide cross-linking based on ectopic Cys residues showed that the contacts between Gag proteins on the membrane are similar to the known contacts in virus-like particles. Taken together, we interpret these results to mean that Gag membrane interaction is cooperative in that it depends on the ability of Gag to multimerize. IMPORTANCE The retroviral structural protein Gag has three major domains. The N-terminal MA domain interacts directly with the plasma membrane (PM) of cells. The central CA domain, together with immediately adjoining sequences, facilitates the assembly of thousands of Gag molecules into a lattice. The C-terminal NC domain interacts with the genome, resulting in packaging of viral RNA. For assembly in vitro with purified Gag, in the absence of membranes, binding of NC to nucleic acid somehow facilitates further Gag-Gag interactions that lead to formation of the Gag lattice. The contributions of MA-mediated membrane binding to virus particle assembly are not well understood. Here, we report that in the absence of nucleic acid, membranes provide a platform that facilitates Gag-Gag interactions. This study demonstrates that the binding of Gag, but not of MA, to membranes is cooperative and identifies SPA as a major factor that controls this cooperativity.
Genetically Engineered Virus-Vectored Vaccines – Environmental Risk Assessment and Management Challenges

Genetically engineered or modified viruses (GMVs) are being increasingly used as live vaccine vectors and their applications may have environmental implications that must be taken into account in risk assessment and management processes. In most legislative frameworks GMVs are treated as GMOs (genetically modified organisms), which require ERA (environmental risk assessment) in addition to the evaluation of the quality, safety and efficacy of the product before marketing authorization or clinical trial applications are submitted. The ERA is performed in order to identify the potential risks for public health and the environment that may arise due to the use and release of GMVs. If risks are identified and considered as not acceptable, the ERA process should go on to propose appropriate risk management strategies capable to reduce these risks (Anliker et al., 2010; Kühler et al, 2009).
Genetics, local environment and health as factors influencing plasma carotenoids in wild American kestrels (Falco sparverius)

Carotenoids are important as pigments for bright coloration of animals, and as physiologically active compounds with a wide array of health–related functions. Carotenoid–dependent coloration may have evolved as a signal to conspecifics; however, factors that may limit availability of carotenoids are poorly known. We investigated how the acquisition of carotenoids may be constrained by availability in the environment, diet, genetic make–up and health status of wild American kestrels (Falco sparverius). Plasma concentrations of siblings at the time of fledging showed a high degree of resemblance; however, a cross–fostering experiment revealed that variance was largely explained by nest of rearing, rather than nest of origin, thus indicating a low genetic component. A multivariate analysis of attributes of nestlings (sex, size, plasma proteins, immune function), parental reproduction (laying date, clutch size) and rearing conditions (brood size, size hierarchy, nestling mortality) showed only a small significant effect of leucocyte differentials on carotenoid concentrations of nestlings. A strong environmental effect on plasma carotenoids was demonstrated by levels of adult kestrels being correlated within mated pairs, and having a significant association with the abundance of voles, the primary prey species, per territory.
Dexamethasone-Mediated Up-Regulation of the Mannose Receptor Improves the Delivery of Recombinant Glucocerebrosidase to Gaucher Macrophages

Enzyme replacement therapy for Gaucher disease uses a recombinant glucocerebrosidase (Cerezyme) whose oligosaccharide chains have been remodeled to expose the core mannose residues. This modification promotes the uptake of the hydrolase by Gaucher-affected macrophages via mannose receptor-mediated endocytosis. However, studies revealed that amounts of the infused enzyme were also delivered to other mannose receptor-bearing cells such as the liver sinusoidal endothelial cells. To maximize the delivery of Cerezyme to macrophages, agents that increased the cell surface levels of the mannose receptor specifically on macrophages were examined. Treatment with dexamethasone improved the in vitro uptake of Cerezyme by a macrophage but not by liver sinusoidal endothelial or hepatocyte cell lines. The enhanced uptake by the macrophages was due to an increase in surface mannose receptors because the activity could be blocked by the addition of mannans. Pretreatment of rats with the glucocorticoid also preferentially enhanced the delivery of Cerezyme to the Kupffer cells and splenic macrophages. This effect of dexamethasone also applied to substrate-laden macrophages isolated from Niemann-Pick A mice. Together, these data suggest that pretreatment with dexamethasone could specifically enhance the presentation of mannose receptors on Gaucher macrophages with resultant improvement in delivery of the enzyme to the affected cells.
The Role of CD 44 in Concanavalin A-Induced Hepatitis

s: Chen D, Nagarkatti P, and Nagarkatti M. (2000) Role of CD44 in Con-A induced Hepatitis. 20 Annual Seminar of Cancer Researchers in Virginia. EVMS, Norfolk, VA. Chen D, Nagarkatti P and Nagarkatti M. (2000) Role of CD44 in Con-A induced Hepatitis. IMMUNOLOGY 2000 AAI/CIS Joint Annual Meeting, Seattle, Washington. Presentations at Meetings: Chen D, Nagarkatti P, and Nagarkatti M. (2000) Role of CD44 in Con-A induced Hepatitis. 20 Annual Seminar of Cancer Researchers in Virginia. EVMS, Norfolk, VA. Chen D, Nagarkatti P and Nagarkatti M. (2000) Role of CD44 in Con-A induced Hepatitis. IMMUNOLOGY 2000 AAI/CIS Joint Annual Meeting, Seattle, Washington.
Automatic control of LH and FSH secretion by short feedback circuits in immature rats.

Immature rats 31–32 days old received intracerebral implants of LH, FSH and cholesterol. Twenty-seven gauge needles loaded at the tip with LH or FSH were stereotaxically implanted in the medial basal hypothalamus (MBH) and into the adenohypophysis; other animals were also implanted with FSH in the septum, rostral hypothalamus and subcutaneously. LH median eminence implants induced, 10–18 days later, a marked atrophy of the ovaries (p<0.005), and the percentage of rats which presented corpora lutea (CL) was significantly less than controls (16.6 vs. 75.6%; p<0.005). Rats with LH implanted in other areas did not modify their ovarian weight, and the percentage of CL was similar to controls. Animals with intrapituitary LH behaved as controls. Rats withimplants of FSH in the MBH and killed 7–12 days later did not present atrophy of the ovaries, and the histology showed a clear stimulation of the interstitial tissue with luteinization and multiple presence of CL. The percentage of rats with CL killed 4–12 days .
Robotics in the Classroom: Providing Robotics Equipment to Support Intelligent Systems Curricula

The authors present how the Institute for Research in Intelligent Systems (IRIS) at California State University, Chico (CSUC) provides access to robotics equipment to support courses in intelligent systems. The supported courses range from core courses in computer science, general education courses, and senior project courses in computer science and in engineering.
Facetted Browsing on Extracted Fusion Tables Data for Digital Cities

Digital cities of the future should provide digital information about points-of-interest (POIs) for virtually any user context. Starting from several Google Fusion tables about city POIs, we extracted and transferred useful POI data to RDF to be accessible by SPARQL requests. In this initial application context, we concentrated on museum and restaurant resources as the result of a precision-oriented information extraction part. With the current application system we are able to retrieve, filter, and order digital cities POI data in multiple ways. With the help of facets, users can do more than just browsing the museums and restaurants. They can filter the relevant objects according to available metadata criteria such as city, country, and POI categories. Different views allow us to visualize the objects of interest as tables, thumbnails, or POIs on an interactive map. In addition, any complementary information on the cities where museums and restaurants are located are retrieved from DBpedia and displayed at query time.
Developmental expression of the prolactin receptor gene in rat gonads.

The prolactin receptor (PRLR) is a member of the cytokine/prolactin/GH receptor family, and it is widely expressed in various mammalian tissues. Expression of the two different forms of PRLR, differing in the length of their cytoplasmic domains, was studied in rat gonads during fetal and postnatal development. The two forms of PRLR mRNA were analyzed by reverse transcription (RT)-PCR using primer pairs specific for the different forms. The specificity of the cDNA species generated by RT-PCR was verified by Southern hybridization using nested 32P-labeled oligonucleotides. The results indicated that both forms of PRLR mRNA are expressed in the rat testis and ovary, which is in agreement with previous reports. The onset of expression of the two PRLR forms occurs on day 14.5 of fetal life in rat testis. In the ovary, the long form of PRLR mRNA appears 1 day before the short form, i.e. these forms begin to be expressed on fetal days 14.5 and 15.5 respectively. In situ hybridization with antisense cRNA probes specific to each form of the PRLR mRNAs demonstrated specific hybridization of both forms, localized in Leydig cells from day 18.5 of fetal life and at the postnatal ages studied. Compared with our previous findings concerning the ontogeny of LH receptor gene expression, PRLR gene expression starts earlier in development and exhibits no sexual dimorphism. The presence of two forms of PRLR mRNA in the fetal gonads suggest that they might play differential roles in gonadal development and function.
Differential Roles of HOW in Male and Female Drosophila Germline Differentiation

The adult gonads in both male and female Drosophila melanogaster produce gametes that originate from a regenerative pool of germline stem cells (GSCs). The differentiation programme that produces gametes must be co-ordinated with GSC maintenance and proliferation in order to regulate tissue regeneration. The HOW RNA-binding protein has been shown to maintain mitotic progression of male GSCs and their daughters by maintenance of Cyclin B expression as well as suppressing accumulation of the differentiation factor Bam. Loss of HOW function in the male germline results in loss of GSCs due to a delay in G2 and subsequent apoptosis. Here we show that female how mutant GSCs do not have any cell cycle defects although HOW continues to bind bam mRNA and suppress Bam expression. The role of HOW in suppressing germ cell Bam expression appears to be conserved between sexes, leading to different cellular outcomes in how mutants due to the different functions of Bam. In addition the role in maintaining Cyclin B expression has not been conserved so female how GSCs differentiate rather than arrest.
Serotonin and noradrenaline reuptake inhibitors in animal models of pain

Animal models of chronic pain serve as an experimental basis for testing new therapeutic interventions and for mechanistic investigations. In an animal model of chronic pain, based on the injection of formalin into the paw of a rodent, inhibitors of noradrenaline reuptake such as nisoxetine, nortriptyline and maprotiline and dual inhibitors of the noradrenaline andserotonin reuptake such as imipramine and milnacipran produce potent anti‐nociceptive effects, whereas selective serotonin reuptake inhibitors, such as fluvoxamine, are much less potent. In another model, neuropathicpain resulting from the chronic constriction injury of the sciatic nerve was prevented by the dual uptake inhibitor, venlafaxine. The experimental model involving ligation of the 5th spinal nerve induces behavioural signs in rats and mice that are similar to the symptoms of human neuropathic pain. In this model amitriptyline, a non‐selective serotonin and noradrenaline reuptake blocker, the preferential noradrenaline reuptake inhibitor, desipramine and the selective serotonin and noradrenaline reuptake inhibitors, milnacipran and duloxetine, produce a decrease in pain sensitivity whereas the selective serotonin reuptake inhibitor, fluoxetine, is ineffective. Antidepressants acting on the noradrenergic or both the noradrenergic and serotonergic systems thus appear to be more effective than those working on the serotonin system alone. Copyright © 2004 John Wiley & Sons, Ltd.
The PSP‐associated MAPT H1 subhaplotype in Guadeloupean atypical Parkinsonism

The aim of this study was to determine whether the H1 subhaplotype in MAPT associated with progressive supranuclear palsy (PSP) in Caucasians confers risk for PSP‐like atypical parkinsonism in Guadeloupe, a tauopathy. Guadeloupean controls and patients with atypical and idiopathic parkinsonism and ethnically and age‐matched controls were genotyped for H1 and H2 alleles, then for the H1 subhaplotype associated with PSP in Caucasians, using previously described haplotype‐tagging single nucleotide polymorphisms (Ht‐SNPs) in linkage disequilibrium at the MAPT locus. Most Guadeloupean controls and patients were homozygous for the H1 allele; only 5% were heterozygous for the H2 allele, consistent with the European contribution to the racial admixture in Guadeloupe, but equivalent to the frequency found in Caucasian PSP patients. The frequencies of the Ht‐SNPs used to determine the PSP‐associated H1 subhaplotype in both Guadeloupean controls and parkinsonians were similar, indicating that the H1 subhaplotype associated with PSP in Caucasians was not a risk factor for PSP‐like atypical parkinsonism in Guadeloupe. Interestingly, they were also similar to the frequencies in Caucasian PSP patients. The major H1 subhaplotype in Guadeloupe, determined by analysis of linkage desequibrium, differed from the major Caucasian subhaplotype, but corresponded to minor alleles previously described. © 2008 Movement Disorder Society
Kriminologie und forensische Kinder- und Jugendpsychiatrie: Die Bedeutung der Entwicklungsperspektive

Criminology and Forensic Child and Adolescent Psychiatry (FCAP) have several fields of interest in common, but there are also differences. Whereas criminology is based upon several disciplines, FCAP has its roots in medicine and is based upon a more or less uniform and standardized training curriculum. This does not apply to criminology as an interdisciplinary field of activity with remarkable differences between countries and cultures. In Germany, criminology is not an independent scientific discipline, but a complementary subject within the faculties of law, psychology or sociology. However, both disciplines have quite a large number of research fields in common, especially with regard to causes and background of delinquent behaviour, recidivism and prevention.
A low power high speed accumulator for DDFS applications

An accumulator optimised for use in a Direct Digital Frequency Synthesis (DDFS) system with 24 bits of frequency resolution and 13 bits of phase resolution is presented. Update rates in excess of 800 MHz are achieved by careful choice of architecture. Power dissipation is lowered by removing redundant circuitry. The static, D-type flip flops used in the pipeline architecture are the dominant source of power dissipation. Hence the refresh-every-cycle operation of accumulators in DDFS is exploited by using dynamic delay elements to reduce power consumption.
Sensory Processing in Children with Autism Spectrum Disorder and/or Attention Deficit Hyperactivity Disorder in the Home and Classroom Contexts

Children with neurodevelopmental disorders often show impairments in sensory processing (SP) and higher functions. The main objective of this study was to compare SP, praxis and social participation (SOC) in four groups of children: ASD Group (n = 21), ADHD Group (n = 21), ASD+ADHD Group (n = 21), and Comparison Group (n = 27). Participants were the parents and teachers of these children who were 5–8 years old (M = 6.32). They completed the Sensory Processing Measure (SPM) to evaluate the sensory profile, praxis and SOC of the children in both the home and classroom contexts. In the home context, the most affected was the ASD+ADHD group. The ADHD group obtained higher scores than the ASD group on the Body Awareness (BOD) subscale, indicating a higher level of dysfunction. The ASD group, however, did not obtain higher scores than the ADHD group on any subscale. In the classroom context, the most affected were the two ASD groups: the ASD+ADHD group obtained higher scores than the ADHD group on the Hearing (HEA) and Social Participation (SOC) subscales, and the ASD group obtained higher scores than the ADHD group on the SOC subscale. Regarding sensory modalities, difficulties in proprioception seem to be more characteristic to the ADHD condition. As for higher-level functioning, social difficulties seem to be more characteristic to the ASD condition. Differences between the two contexts were only found in the ASD group, which could be related to contextual hyperselectivity, an inherent autistic feature. Despite possible individual differences, specific intervention programs should be developed to improve the sensory challenges faced by children with different diagnoses.
Individual ovarian volumes obtained from 2D and 3D ultrasound lack precision Running Title Precision of ovarian volume measurements Authors

Objective – To assess the precision of individual ovarian volume measurements by 2D and 3D transvaginal ultrasound scan. Study Design – Transvaginal 2D and 3D ultrasound examinations were performed on 49 women attending a tertiary centre for investigation or treatment for subfertility. Two observers calculated ovarian volume, using both the prolate ellipsoid formula and virtual organ computer-aided analysis (VOCAL), with rotation steps of 30 degrees (3D-30).
Data structuring and effective retrieval in the mining of web sequential characteristic

The Web data mining based on sequential characteristics is a mining technology focusing on text data on Web pages and link structure and combing sequential characteristics on the basis of the mining of Web structure and Web contents. A huge number of data information is carried on Web, and it is increased at a geometric speed every day. As time goes by, the effectiveness of a great number of data is continuously reduced, and they even become completely useless. How to clean these useless data, find out hidden regular contents among a great number of data, and solve the quality problem of data application has become the research hotspot in the Web data mining technology at present. All the information objects on Web can be generally divided into two categories: Structured data and semi-structured data. Those that can be expressed in database structure are called structured data; those expressed in various forms with text as representative are called semi-structured data. The greatest feature of Web data is semi-structuring. Such kind of semi-structured data are relevant to time sequence, meanwhile, time effect of data is also related to time sequence. In the article, discussion is made about how to use the sequential characteristic in the course of Web data mining to carry out structural transfer of semi-structured data based on time effect of data, that is the structuring of Web data, and solve the problem about effectiveness in retrieval accordingly.
Phospholipase C in Beijing strains of Mycobacterium tuberculosis

Background and Objectives Phospholipase of Mycobacterium tuberculosis plays an important role in pathogenesis through breaking up phospholipids and production of diacylglycerol. In this study, we examined the Beijing strains of Mycobacterium tuberculosis isolated from Iranian patients for the genes encoding this enzyme. Materials and Methods DNA extraction was performed using CTAB (cetyltrimethylammonium bromide) from positive culture specimens in tuberculosis patients. PCR was then used to amplify the plcA, plcB, plcC genes of Beijing strain, and non-Beijing strains were identified by spoligotyping. Results Of 200 specimens, 19 (9.5%) were Beijing strain and 181 (90.5%) were non-Beijing strains. The results of PCR for Beijing strains were as follows: 16 strains (84.2%) were positive for plcA, 17 (89.4%) were positive for plcB and 17 (89.4%) were positive for plcC genes. The standard strain (H37RV) was used as control. Conclusion The majority of Beijing strains have phospholipase C genes which can contribute to their pathogenesis but we need complementary studies to confirm the role of phospholipase C in pathogenecity of Mycobacterium tuberculosis.