bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis B Virus Capsid Assembly Is Enhanced by Naturally Occurring Mutation F97L
Authors: Ceres Pablo , Stray Stephen J. , Zlotnick Adam 
Published: August 2004

ABSTRACT
In chronic hepatitis B virus (HBV) infections, one of the most common mutations to the virus occurs at amino acid 97 of the core protein, where leucine replaces either phenylalanine or isoleucine, depending on strain. This mutation correlates with changes in viral nucleic acid metabolism and/or secretion. We hypothesize that this phenotype is due in part to altered core assembly, a process required for DNA synthesis. We examined in vitro assembly of empty HBV capsids from wild-type and F97L core protein assembly domains. The mutation enhanced both the rate and extent of assembly relative to those for the wild-type protein. The difference between the two proteins was most obvious in the temperature dependence of assembly, which was dramatically stronger for the mutant protein, indicating a much more positive enthalpy. Since the structures of the mutant and wild-type capsids are essentially the same and the mutation is not involved in the contact between dimers, we suggest that the F97L mutation affects the dynamic behavior of dimer and capsid.
Measles Virus Interacts with and Alters Signal Transduction in T-Cell Lipid Rafts
Authors: Avota Elita , Müller Nora , Klett Maren , Schneider-Schaulies Sibylle 
Published: August 2004

ABSTRACT
By a contact-dependent surface interaction, the measles virus (MV) glycoprotein complex induces a pronounced inhibition of T-cell proliferation. We now show that MV directly interacts with glycosphingolipid-enriched membrane microdomains on human primary T cells and alters recruitment and segregation of membrane proximal signaling components. Contact-dependent interference with T-cell receptor-stimulated tyrosine phosphorylation and Ca mobilization is a late event seen 24 h after MV treatment. In contrast, stimulated recruitment of pleckstrin homology domain-containing proteins such as Akt and Vav is inhibited early after MV contact, as is segregation of the activated Akt kinase from rafts. Tyrosine phosphorylation of the regulatory subunit of the phosphatidylinositol 3-kinase (PI3K), p85, is apparently normal then, yet this protein fails to partition to the lipid raft fraction, and this is associated with stable expression of its negative regulator Cbl-b. Thus, by interaction with lipid rafts, MV contact initially targets recruitment of PI3K by preventing stimulated Cbl-b degradation and activation of PI3K-dependent signaling components.
Characterization of the Human Cytomegalovirus UL34 Gene
Authors: Biegalke B. J. , Lester E. , Branda A. , Rana R. 
Published: August 2004

ABSTRACT
UL34 encodes the transcriptional repressor of the human cytomegalovirus immune evasion gene, US3, and is essential for viral replication in tissue culture. Two different monocistronic transcripts originate from UL34 at early and late times postinfection and encode two predominant proteins and a third, minor protein. The UL34 proteins are differentially expressed throughout the viral replication cycle, with both proteins localizing to the nucleus and repressing expression of the US3 gene.
α(1,3)Fucosyltransferases FucT-IV and FucT-VII Control Susceptibility to Atherosclerosis in Apolipoprotein E−/− Mice
Authors: Homeister Jonathon W. , Daugherty Alan , Lowe John B. 
Published: August 2004

Objective—These studies examine the contributions of α(1,3)fucosyltransferases (FucT) IV and VII to the generation of selectin counter-receptors necessary for selectin-dependent atherogenesis. They also determine the functional contribution of FucT-IV and FucT-VII to shear-dependent tethering of monocytes to P-selectin, a process believed to be required for atherogenesis.Methods and Results—Atherosclerotic lesion size and histology were determined in apolipoprotein E−/− mice sufficient or deficient in FucT-IV or FucT-VII. Lesion size was subtly reduced in FucT-IV–deficient mice and significantly reduced in FucT-VII–deficient mice. FucT deficiency did not alter lesion histology, plasma total cholesterol, or the lipoprotein distribution profile. Atheroprotection in FucT-IV or FucT-VII deficiency aligned with subtle and profound reductions, respectively, of P-selectin counter-receptor activity on peripheral blood monocytes as determined by tethering to P-selectin-IgG in vitro under shear flow.Conclusions—FucT-VII–mediated α(1,3)fucosylation of selectin ligands is a necessary concomitant to atherogenesis in apoE−/− mice and is required for P-selectin–dependent peripheral blood monocyte adhesion under shear stress. FucT-IV deficiency yields subtle deficits in monocyte P-selectin counter-receptor activity and is associated with a subtle decrement in atherosclerosis. These studies identify an important role for FucT-VII in atherogenesis, and a subsidiary role for FucT-IV, and implicate leukocyte selectin counter-receptors in the pathogenesis of atherosclerosis.
Gushist and Qutbian Approaches to Government: A Comparative Analysis of Religious Assassination
Authors: Kiener Ronald 
Published: August 2004

AbstractThe disciples and pseudo-followers of the religious ideologues Sayyid Qutb and Rabbi Zvi Yehudah Kook have now lived without their mentors for more than twentyfive years (in the case of Qutb) and for more than a decade (in the case of Kook). In both instances, putative “disciples” of these thinkers committed assassinations of the acknowledged domestic leader of a sitting government: Sadat in 1981 by al-Jihad al-Islami; Rabin in 1995 by Eyal. In this paper, the theories of both mentors and their ersatz disciples on the issue of violence against the sitting government will be examined for possible comparative results. Rather than finding a symmetry in these examples of Middle Eastern fundamentalist violence, the author elaborates a sharp difference between the two: one (Islam) is centered on the issue of apostasy, while the other (Judaism) is centered on the issue of communal rights and protections. Rather than providing a point for drawing similarities, fundamentalist-inspired assassination points out the differences between Israeli-Jewish and Egyptian-Islamic fundamentalisms.
Gift and Return Gift, Greeting and Return Greeting in India.
Authors: Michaels Axel 
Published: August 2004

AbstractIn a remarkable, often quoted footnote of his famous “Essai sur le don,” Marcel Mauss wonders that traditional Hindu law does not really prescribe the obligation to return a gift (Skt. dāna). According to some authors (J. Parry, Th. Trautmann, G. Raheja et al.) Mauss has demonstrated by this footnote his lack of a firm grasp of the theory of dāna since he did not notice that a dāna contains too much impurity or inauspiciousness to return to its donor. On the basis of striking parallels between the Śāstric theories of greeting (abhivādanadharma) and gift-giving (dānadharma), this paper questions the aspect of impurity in the gift and argues that kingly generosity or liberality and the meritious attitudes of asceticism have been the major source for giving gifts.
Immature dendritic cell transdifferentiation into osteoclasts: a novel pathway sustained by the rheumatoid arthritis microenvironment
Authors: Rivollier Aymeric , Mazzorana Marlène , Tebib Jacques , Piperno Muriel , Aitsiselmi Tarik , Rabourdin-Combe Chantal , Jurdic Pierre , Servet-Delprat Christine 
Published: August 2004

AbstractDendritic cells (DCs), the mononuclear cells that initiate immune response, and osteoclasts, the multinucleated bone-resorbing cells, are derived from monocyte/macrophage precursor cells. Granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor (M-CSF) reciprocally regulate the differentiation of both lineages in mice. Using human monocyte-derived DCs generated in vitro, we show that immature DCs transdifferentiate into functional osteoclasts (OCs) in the presence of M-CSF and receptor activator of nuclear factor-κB ligand (RANKL). Transdifferentiation operates through fusion of intermediate adherent bipolar fusiform mononuclear cells expressing CD14, CD1a, and RANKL and able to induce RANKL+ T-cell proliferation. Surprisingly, DC fusion in vitro is faster and more efficient than monocyte fusion to form multinucleated giant cells. The transdifferentiation process reported here supports the existence of a high cellular plasticity within differentiated myeloid phagocytes. Importantly, this process is greatly enhanced by rheumatoid arthritis synovial fluid and involves proinflammatory cytokines such as interleukin 1 or tumor necrosis factor α, as well as components of the extracellular matrix such as hyaluronic acid. Our data therefore suggest that DC-derived OCs may be directly involved in the osteolytic lesions observed in human inflammatory bone diseases such as rheumatoid arthritis or in particular forms of Langerhans cell histiocytosis, characterized by accumulation of immature skin DCs and chronic lytic bone lesions. (Blood. 2004;104:4029-4037)
Unusual late presentation of X-linked chronic granulomatous disease in an adult female with a somatic mosaic for a novel mutation in CYBB
Authors: Wolach Baruch , Scharf Yitshak , Gavrieli Ronit , de Boer Martin , Roos Dirk 
Published: August 2004

AbstractMost patients with chronic granulomatous disease (CGD) have mutations in the X-linked CYBB gene that encodes gp91phox, a component of the phagocyte NADPH oxidase. The resulting X-linked form of CGD is usually manifested in boys. Rarely, X-CGD is encountered in female carriers with extreme expression of the mutated gene. Here, we report on a woman with a novel mutation in CYBB (CCG[90-92] → GGT), predicting Tyr30Arg31 → stop, Val in gp91phox, who presented with clinical symptoms at the age of 66. The mutation was present in heterozygous form in genomic DNA from her leukocytes but was fully expressed in mRNA from these cells, indicating that in her leukocytes the X chromosome carrying the nonmutated CYBB allele had been inactivated. Indeed, only 0.4% to 2% of her neutrophils showed NADPH oxidase activity. This extreme skewing of her X-chromosome inactivation was not found in her cheek mucosal cells and is thus not due to a general defect in gene methylation on one X chromosome. Moreover, the CYBB mutation was not present in the DNA from her cheek cells and was barely detectable in the DNA from her memory T lymphocytes. Thus, this patient shows a somatic mosaic for the CYBB mutation, which probably originated during her lifetime in her bone marrow.
Ligation of lymphocyte function-associated antigen-1 on monocytes decreases very late antigen-4-mediated adhesion through a reactive oxygen species-dependent pathway
Authors: Chuang Kuo-Pin , Huang Ya-Fang , Hsu Yi-Ling , Liu Hsiao-Sheng , Chen Hong-Chen , Shieh Chi-Chang 
Published: August 2004

AbstractMonocyte-endothelial adhesion plays an important role in monocyte trafficking and hence is important for immune responses and pathogenesis of inflammatory diseases including atherosclerosis. The cross-talk between different integrins on monocytes may be crucial for a coordinated regulation of the cellular adhesion during the complex process of transendothelial migration. By using monoclonal antibodies and recombinant intercellular adhesion molecule 1 (ICAM-1) to engage lymphocyte function-associated antigen 1 (LFA-1) on monocytic cells, we found that the cellular adhesion to vascular cell adhesion molecule 1 (VCAM-1) mediated by very late antigen 4 (VLA-4) was suppressed after this treatment and the suppression depended on the presence of reactive oxygen species (ROSs). Inhibition of production of ROSs through the use of inhibitor of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, but not inhibitors of mitochondrial electron transport chain or xanthine oxidase, revealed that this suppression on VLA-4-mediated cellular binding was mediated by ROSs produced by phagocyte NADPH oxidase. Activation of phosphoinositol-3 kinase and Akt appears to mediate this NADPH oxidase activation through p47phox phosphorylation and Rac-1 activation. Our results provide a novel pathway in which ROSs play a critical role in integrin cross-talk in monocytes. This signaling pathway may be important for cellular transition from firm arrest to diapedesis during monocyte trafficking. (Blood. 2004;104:4046-4053)
STING Millennium Suite: integrated software for extensive analyses of 3d structures of proteins and their complexes
Authors: Higa Roberto H , Togawa Roberto C , Montagner Arnaldo J , Palandrani Juliana CF , Okimoto Igor KS , Kuser Paula R , Yamagishi Michel EB , Mancini Adauto L , Neshich Goran 
Published: August 2004

Abstract
Background
The integration of many aspects of protein/DNA structure analysis is an important requirement for software products in general area of structural bioinformatics. In fact, there are too few software packages on the internet which can be described as successful in this respect. We might say that what is still missing is publicly available, web based software for interactive analysis of the sequence/structure/function of proteins and their complexes with DNA and ligands. Some of existing software packages do have certain level of integration and do offer analysis of several structure related parameters, however not to the extent generally demanded by a user.

Results
We are reporting here about new Sting Millennium Suite (SMS) version which is fully accessible (including for local files at client end), web based software for molecular structure and sequence/structure/function analysis. The new SMS client version is now operational also on Linux boxes and it works with non-public pdb formatted files (structures not deposited at the RCSB/PDB), eliminating earlier requirement for the registration if SMS components were to be used with user's local files. At the same time the new SMS offers some important additions and improvements such as link to ProTherm as well as significant re-engineering of SMS component ConSSeq. Also, we have added 3 new SMS mirror sites to existing network of global SMS servers: Argentina, Japan and Spain.

Conclusion
SMS is already established software package and many key data base and software servers worldwide, do offer either a link to, or host the SMS. SMS (S ting M illennium S uite) is web-based publicly available software developed to aid researches in their quest for translating information about the structures of macromolecules into knowledge. SMS allows to a user to interactively analyze molecular structures, cross-referencing visualized information with a correlated one, available across the internet. SMS is already used as a didactic tool by some universities. SMS analysis is now possible on Linux OS boxes and with no requirement for registration when using local files.
Extrinsic factors regulate partial agonist efficacy of strychnine-sensitive glycine receptors
Authors: Farroni Jeffrey S , McCool Brian A 
Published: August 2004

Abstract
Background
Strychnine-sensitive glycine receptors in many adult forebrain regions consist of alpha2 + beta heteromeric channels. This subunit composition is distinct from the alpha1 + beta channels found throughout the adult spinal cord. Unfortunately, the pharmacology of forebrain alpha2beta receptors are poorly defined compared to 'neonatal' alpha2 homomeric channels or 'spinal' alpha1beta heteromers. In addition, the pharmacologic properties of native alpha2beta glycine receptors have been generally distinct from receptors produced by heterologous expression. To identify subtype-specific pharmacologic tools for the forebrain alpha2beta receptors, it is important to identify a heterologous expression system that closely resembles these native glycine-gated chloride channels.

Results
While exploring pharmacological properties of alpha2beta glycine receptors compared to alpha2-homomers, we found that distinct heterologous expression systems appeared to differentially influence partial agonist pharmacology. The β-amino acid taurine possessed 30–50% efficacy for alpha2-containing receptor isoforms when expressed in HEK 293 cells. However, taurine efficacy was dramatically reduced in L-cell fibroblasts. Similar results were obtained for β-alanine. The efficacy of these partial agonists was also strongly reduced by the beta subunit. There were no significant differences in apparent strychnine affinity values calculated from concentration-response data between expression systems or subunit combinations. Nor did relative levels of expression correlate with partial agonist efficacy when compared within or between several different expression systems. Finally, disruption of the tubulin cytoskeleton reduced the efficacy of partial agonists in a subunit-dependent, but system-independent, fashion.

Conclusions
Our results suggest that different heterologous expression systems can dramatically influence the agonist pharmacology of strychnine-sensitive glycine receptors. In the systems examine here, these effects are independent of both absolute expression level and any system-related alterations in the agonist binding site. We conclude that complex interactions between receptor composition and extrinsic factors may play a significant role in determining strychnine-sensitive glycine receptor partial agonist pharmacology.
DMBT1 expression is down-regulated in breast cancer
Authors: Braidotti P , Nuciforo PG , Mollenhauer J , Poustka A , Pellegrini C , Moro A , Bulfamante G , Coggi G , Bosari S , Pietra GG 
Published: August 2004

Abstract
Background
We studied the expression of DMBT1 (deleted in malignant brain tumor 1), a putative tumor suppressor gene, in normal, proliferative, and malignant breast epithelium and its possible relation to cell cycle.

Methods
Sections from 17 benign lesions and 55 carcinomas were immunostained with anti DMBT1 antibody (DMBTh12) and sections from 36 samples, were double-stained also with anti MCM5, one of the 6 pre-replicative complex proteins with cell proliferation-licensing functions. DMBT1 gene expression at mRNA level was assessed by RT-PCR in frozen tissues samples from 39 patients.

Results
Normal glands and hyperplastic epithelium in benign lesions displayed a luminal polarized DMBTh12 immunoreactivity. Normal and hyperplastic epithelium adjacent to carcinomas showed a loss of polarization, with immunostaining present in basal and perinuclear cytoplasmic compartments. DMBT1 protein expression was down-regulated in the cancerous lesions compared to the normal and/or hyperplastic epithelium adjacent to carcinomas (3/55 positive carcinomas versus 33/42 positive normal/hyperplastic epithelia; p = 0.0001). In 72% of cases RT-PCR confirmed immunohistochemical results. Most of normal and hyperplastic mammary cells positive with DMBTh12 were also MCM5-positive.

Conclusions
The redistribution and up-regulation of DMBT1 in normal and hyperplastic tissues flanking malignant tumours and its down-regulation in carcinomas suggests a potential role in breast cancer. Moreover, the concomitant expression of DMTB1 and MCM5 suggests its possible association with the cell-cycle regulation.
Intrathecal baclofen withdrawal syndrome- a life-threatening complication of baclofen pump: A case report
Authors: Mohammed Imran , Hussain Asif 
Published: August 2004

Abstract
Background
Intrathecal baclofen pump has been used effectively with increasing frequency in patients with severe spasticity, particularly for those patients who are unresponsive to conservative pharmacotherapy or develop intolerable side effects at therapeutic doses of oral baclofen. Drowsiness, nausea, headache, muscle weakness, light-headedness and return of pretreatment spasticity can be caused by intrathecal pump delivering an incorrect dose of baclofen. Intrathecal baclofen withdrawal syndrome is a very rare, potentially life-threatening complication of baclofen pump caused by an abrupt cessation of intrathecal baclofen.

Case presentation
A 24-year-old man with a past medical history of cerebral palsy and spastic quadriparesis developed hyperthermia, disseminated intravascular coagulation, rhabdomyolysis, acute renal failure and multisystem organ failure leading to a full-blown intrathecal baclofen withdrawal syndrome. Intrathecal baclofen pump analysis revealed that it was stopped due to some programming error. He was treated effectively with supportive care, high-dose benzodiazepines and reinstitution of baclofen pump.

Conclusion
The episodes of intrathecal baclofen withdrawal syndrome are mostly caused by preventable human errors or pump malfunction. Educating patients and their caregivers about the syndrome, and regular check-up of baclofen pump may decrease the incidence of intrathecal baclofen withdrawal syndrome. Oral baclofen replacement may not be an effective method to treat or prevent intrathecal baclofen withdrawal syndrome. Management includes an early recognition of syndrome, proper intensive care management, high-dose benzodiazepines and prompt analysis of intrathecal pump with reinstitution of baclofen.
Hereditary 1,25-Dihydroxyvitamin D Resistant Rickets due to a Mutation Causing Multiple Defects in Vitamin D Receptor Function
Authors: Malloy Peter J. , Xu Rong , Peng Lihong , Peleg Sara , Al-Ashwal Abdullah , Feldman David 
Published: August 2004

Abstract
Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disease caused by mutations in the vitamin D receptor (VDR). We studied a young Saudi Arabian girl who exhibited the typical clinical features of HVDRR, but without alopecia. Analysis of her VDR gene revealed a homozygous T to C mutation in exon 7 that changed isoleucine to threonine at amino acid 268 (I268T). From crystallographic studies of the VDR ligand-binding domain, I268 directly interacts with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and is involved in the hydrophobic stabilization of helix H12. We recreated the I268T mutation and analyzed its effects on VDR function. In ligand binding assays, the I268T mutant VDR exhibited an approximately 5- to 10-fold lower affinity for [3H]1,25(OH)2D3 compared with the wild-type (WT) VDR. The I268T mutant required approximately a 65-fold higher concentration of 1,25(OH)2D3 to be equipotent in gene transactivation. Both retinoid X receptor heterodimerization and coactivator binding were reduced in the I268T mutant. Analogs of 1,25(OH)2D3 have been proposed as potential therapeutics for patients with HVDRR. Interestingly, in protease sensitivity assays, treatment with the potent vitamin D analog, 20-epi-1,25(OH)2D3, stabilized I268T mutant proteolytic fragments better than 1,25(OH)2D3. Moreover, 20-epi-1,25(OH)2D3 restored transactivation of the I268T mutant to levels exhibited by WT VDR treated with 1,25(OH)2D3. In conclusion, we describe a novel mutation, I268T, in the VDR ligand-binding domain that alters ligand binding, retinoid X receptor heterodimerization, and coactivator binding. These combined defects in VDR function cause resistance to 1,25(OH)2D3 action and result in the syndrome of HVDRR.