bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of Nef Downregulates CXCR4, the Major Coreceptor of Human Immunodeficiency Virus, from the Surfaces of Target Cells and Thereby Enhances Resistance to Superinfection
Authors: Venzke Stephanie , Michel Nico , Allespach Ina , Fackler Oliver T. , Keppler Oliver T. 
Published: October 2006

ABSTRACT

Lentiviral Nef proteins are key factors for pathogenesis and are known to downregulate functionally important molecules, including CD4 and major histocompatibility complex class I (MHC-I), from the surfaces of infected cells. Recently, we demonstrated that Nef reduces cell surface levels of the human immunodeficiency virus type 1 (HIV-1) entry coreceptor CCR5 (N. Michel, I. Allespach, S. Venzke, O. T. Fackler, and O. T. Keppler, Curr. Biol. 15:714-723, 2005). Here, we report that Nef downregulates the second major HIV-1 coreceptor, CXCR4, from the surfaces of HIV-infected primary CD4 T lymphocytes with efficiencies comparable to those of the natural CXCR4 ligand, stromal cell-derived factor-1 alpha. Analysis of a panel of mutants of HIV-1
SF2
Nef revealed that the viral protein utilized the same signature motifs for downmodulation of CXCR4 and MHC-I, including the proline-rich motif P
73
P
76
P
79
P
82
and the acidic cluster motif E
66
E
67
E
68
E
69.
Expression of wild-type Nef, but not of specific Nef mutants, resulted in a perinuclear accumulation of the coreceptor. Remarkably, the carboxy terminus of CXCR4, which harbors the classical motifs critical for basal and ligand-induced receptor endocytosis, was dispensable for the Nef-mediated reduction of surface exposure. Functionally, the ability of Nef to simultaneously downmodulate CXCR4 and CD4 correlated with maximum-level protection of Nef-expressing target cells from fusion with cells exposing X4 HIV-1 envelopes. Furthermore, the Nef-mediated downregulation of CXCR4 alone on target T lymphocytes was sufficient to diminish cells' susceptibility to X4 HIV-1 virions at the entry step. The downregulation of chemokine coreceptors is a conserved activity of Nef to modulate infected cells, an important functional consequence of which is an enhanced resistance to HIV superinfection.
Translation of the Flavivirus Kunjin NS3 Gene in
cis
but Not Its RNA Sequence or Secondary Structure Is Essential for Efficient RNA Packaging
Authors: Pijlman Gorben P. , Kondratieva Natasha , Khromykh Alexander A. 
Published: October 2006

ABSTRACT

Our previous studies using
trans
-complementation analysis of Kunjin virus (KUN) full-length cDNA clones harboring in-frame deletions in the NS3 gene demonstrated the inability of these defective complemented RNAs to be packaged into virus particles (W. J. Liu, P. L. Sedlak, N. Kondratieva, and A. A. Khromykh, J. Virol.
76:
10766-10775). In this study we aimed to establish whether this requirement for NS3 in RNA packaging is determined by the secondary RNA structure of the NS3 gene or by the essential role of the translated NS3 gene product. Multiple silent mutations of three computer-predicted stable RNA structures in the NS3 coding region of KUN replicon RNA aimed at disrupting RNA secondary structure without affecting amino acid sequence did not affect RNA replication and packaging into virus-like particles in the packaging cell line, thus demonstrating that the predicted conserved RNA structures in the NS3 gene do not play a role in RNA replication and/or packaging. In contrast, double frameshift mutations in the NS3 coding region of full-length KUN RNA, producing scrambled NS3 protein but retaining secondary RNA structure, resulted in the loss of ability of these defective RNAs to be packaged into virus particles in complementation experiments in KUN replicon-expressing cells. Furthermore, the more robust complementation-packaging system based on established stable cell lines producing large amounts of complemented replicating NS3-deficient replicon RNAs and infection with KUN virus to provide structural proteins also failed to detect any secreted virus-like particles containing packaged NS3-deficient replicon RNAs. These results have now firmly established the requirement of KUN NS3 protein translated in
cis
for genome packaging into virus particles.
Functions of the Stem Region of the Semliki Forest Virus Fusion Protein during Virus Fusion and Assembly
Authors: Liao Maofu , Kielian Margaret 
Published: October 2006

ABSTRACT
Membrane fusion of the alphaviruses is mediated by the E1 protein, a class II virus membrane fusion protein. During fusion, E1 dissociates from its heterodimer interaction with the E2 protein and forms a target membrane-inserted E1 homotrimer. The structure of the homotrimer is that of a trimeric hairpin in which E1 domain III and the stem region fold back toward the target membrane-inserted fusion peptide loop. The E1 stem region has a strictly conserved length and several highly conserved residues, suggesting the possibility of specific stem interactions along the trimer core and an important role in driving membrane fusion. Mutagenesis studies of the alphavirus Semliki Forest virus (SFV) here demonstrated that there was a strong requirement for the E1 stem in virus assembly and budding, probably reflecting its importance in lateral interactions of the envelope proteins. Surprisingly, however, neither the conserved length nor any specific residues of the stem were required for membrane fusion. Although the highest fusion activity was observed with wild-type E1, efficient fusion was mediated by stem mutants containing a variety of substitutions or deletions. A minimal stem length was required but could be conferred by a series of alanine residues. The lack of a specific stem sequence requirement during SFV fusion suggests that the interaction of domain III with the trimer core can provide sufficient driving force to mediate membrane merger.
Molecular polymorphism, differentiation and introgression in the period gene between Lutzomyia intermedia and Lutzomyia whitmani
Authors: Mazzoni Camila J , Souza Nataly A , Andrade-Coelho Claudia , Kyriacou Charalambos P , Peixoto Alexandre A 
Published: October 2006

AbstractBackgroundLutzomyia intermediaandLutzomyia whitmani(Diptera: Psychodidae) are important and very closely related vector species of cutaneous leishmaniasis in Brazil, which are distinguishable by a few morphological differences. There is evidence of mitochondrial introgression between the two species but it is not clear whether gene flow also occurs in nuclear genes.ResultsWe analyzed the molecular variation within the clock geneperiod(per) of these two species in five different localities in Eastern Brazil. AMOVA and Fst estimates showed no evidence for geographical differentiation within species. On the other hand, the values were highly significant for both analyses between species. The two species show no fixed differences and a higher number of shared polymorphisms compared to exclusive mutations. In addition, some haplotypes that are "typical" of one species were found in some individuals of the other species suggesting either the persistence of old polymorphisms or the occurrence of introgression. Two tests of gene flow, one based on linkage disequilibrium and a MCMC analysis based on coalescence, suggest that the two species might be exchanging alleles at theperlocus.ConclusionIntrogression might be occurring betweenL. intermediaandL. whitmaniinperiod, a gene controlling behavioral rhythms inDrosophila. This result raises the question of whether similar phenomena are occurring at other loci controlling important aspects of behavior and vectorial capacity.
Rhythmic expression of the cycle gene in a hematophagous insect vector
Authors: Meireles-Filho Antonio CA , Amoretty Paulo R , Souza Nataly A , Kyriacou Charalambos P , Peixoto Alexandre A 
Published: October 2006

Abstract

Background
A large number of organisms have internal circadian clocks that enable them to adapt to the cyclic changes of the external environment. In the model organism Drosophila melanogaster, feedback loops of transcription and translation are believed to be crucial for the maintenance of the central pacemaker. In this mechanism the cycle (or bmal1) gene, which is constitutively expressed, plays a critical role activating the expression of genes that will later inhibit their own activity, thereby closing the loop. Unlike Drosophila, the molecular clock of insect vectors is poorly understood, despite the importance of circadian behavior in the dynamic of disease transmission.

Results
Here we describe the sequence, genomic organization and circadian expression of cycle in the crepuscular/nocturnal hematophagous sandfly Lutzomyia longipalpis, the main vector of visceral leishmaniasis in the Americas. Deduced amino acid sequence revealed that sandfly cycle has a C-terminal transactivation domain highly conserved among eukaryotes but absent in D. melanogaster. Moreover, an alternative form of the transcript was also identified. Interestingly, while cycle expression in Drosophila and other Diptera is constitutive, in sandflies it is rhythmic in males and female heads but constitutive in the female body. Blood-feeding, which causes down-regulation of period and timeless in this species, does not affect cycle expression.

Conclusion
Sequence and expression analysis of cycle in L. longipalpis show interesting differences compared to Drosophila suggesting that hematophagous vector species might present interesting new models to study the molecular control of insect circadian clocks.
Parents' knowledge and behaviour concerning sunning their babies; a cross-sectional, descriptive study
Authors: Aladag Nihal , Filiz Tuncay M , Topsever Pinar , Gorpelioglu Suleyman 
Published: October 2006

AbstractBackgroundFor centuries, sunlight has been used for therapeutic purposes. Parents still sun their infants to treat neonatal jaundice, nappy rash or mostly to supply vitamin D for bone development as a consequence of health beliefs. In this study we aimed to assess knowledge and behaviour of parents about benefits of sunlight and sun protection.MethodsIn this study, parents attending to governmental primary healthcare units for their children's routine vaccinations, upon their informed consent, were consecutively enrolled during one month. Data were collected by a semi-structured questionnaire.ResultsThe mean age of 118 enrolled parents and their babies were 27.9 ± 6.5 years and 8.3 ± 5.8 months, respectively. Most of the participants were mothers (93.2%), housewives (81.4%) with an educational level of ≥6 years (71.2%). Sunlight was considered beneficial for bone development (86.4%), diaper rash (5.9%) and neonatal jaundice (12.7%). In case of neonatal jaundice 72.0% of the participants reported that they would consult a physician. Most of the participants (82.2%) were sunning their babies outdoors. Nearly half (49.7%) of them got this information from medical staff. Fifty two percent of the parents were sunning their babies before 10–11 a.m. and/or after 3 p.m. Only 13.6% of parents reported using sunscreen for their babies, and the majority of them were using sun protecting factor ≥ 15. One forth of the sunscreen users was using sunscreen according to their physicians' advice.ConclusionMost of the participants were aware of the benefits of sunlight; especially for bone development. However they were displaying inappropriate behaviour while sunning their babies for health reasons. More education should be given to parents about the danger of sunlight at primary health care units while advising to sun their babies, if any.
Deriving utility scores for co-morbid conditions: a test of the multiplicative model for combining individual condition scores
Authors: Flanagan William , McIntosh Cameron N , Le Petit Christel , Berthelot Jean-Marie 
Published: October 2006

Abstract

Background
The co-morbidity of health conditions is becoming a significant health issue, particularly as populations age, and presents important methodological challenges for population health research. For example, the calculation of summary measures of population health (SMPH) can be compromised if co-morbidity is not taken into account. One popular co-morbidity adjustment used in SMPH computations relies on a straightforward multiplicative combination of the severity weights for the individual conditions involved. While the convenience and simplicity of the multiplicative model are attractive, its appropriateness has yet to be formally tested. The primary objective of the current study was therefore to examine the empirical evidence in support of this approach.

Methods
The present study drew on information on the prevalence of chronic conditions and a utility-based measure of health-related quality of life (HRQoL), namely the Health Utilities Index Mark 3 (HUI3), available from Cycle 1.1 of the Canadian Community Health Survey (CCHS; 2000–01). Average HUI3 scores were computed for both single and co-morbid conditions, and were also purified by statistically removing the loss of functional health due to health problems other than the chronic conditions reported. The co-morbidity rule was specified as a multiplicative combination of the purified average observed HUI3 utility scores for the individual conditions involved, with the addition of a synergy coefficient s for capturing any interaction between the conditions not explained by the product of their utilities. The fit of the model to the purified average observed utilities for the co-morbid conditions was optimized using ordinary least squares regression to estimate s. Replicability of the results was assessed by applying the method to triple co-morbidities from the CCHS cycle 1.1 database, as well as to double and triple co-morbidities from cycle 2.1 of the CCHS (2003–04).

Results
Model fit was optimized at s = .99 (i.e., essentially a straightforward multiplicative model). These results were closely replicated with triple co-morbidities reported on CCHS 2000–01, as well as with double and triple co-morbidities reported on CCHS 2003–04.

Conclusion
The findings support the simple multiplicative model for computing utilities for co-morbid conditions from the utilities for the individual conditions involved. Future work using a wider variety of conditions and data sources could serve to further evaluate and refine the approach.
Classification of ductal carcinoma in situ by gene expression profiling
Authors: Hannemann Juliane , Velds Arno , Halfwerk Johannes BG , Kreike Bas , Peterse Johannes L , van de Vijver Marc J 
Published: October 2006

Abstract
Introduction
Ductal carcinoma in situ (DCIS) is characterised by the intraductal proliferation of malignant epithelial cells. Several histological classification systems have been developed, but assessing the histological type/grade of DCIS lesions is still challenging, making treatment decisions based on these features difficult. To obtain insight in the molecular basis of the development of different types of DCIS and its progression to invasive breast cancer, we have studied differences in gene expression between different types of DCIS and between DCIS and invasive breast carcinomas.

Methods
Gene expression profiling using microarray analysis has been performed on 40 in situ and 40 invasive breast cancer cases.

Results
DCIS cases were classified as well- (n = 6), intermediately (n = 18), and poorly (n = 14) differentiated type. Of the 40 invasive breast cancer samples, five samples were grade I, 11 samples were grade II, and 24 samples were grade III. Using two-dimensional hierarchical clustering, the basal-like type, ERB-B2 type, and the luminal-type tumours originally described for invasive breast cancer could also be identified in DCIS.

Conclusion
Using supervised classification, we identified a gene expression classifier of 35 genes, which differed between DCIS and invasive breast cancer; a classifier of 43 genes could be identified separating between well- and poorly differentiated DCIS samples.
Transpalatal approach to deeper cranial structures
Authors: Konrad Horst R. , Canalis Rinaldo Fernando 
Published: October 2006

AbstractThe approach to deep midline cranial structures is technically difficult. The transpalatal approach has a relatively wide exposure as compared to the transnasal, transantral and transethmoidal approches. The added advantage of a medial approach which follows medial landmarks and the flexibility of being able to extend exposure to the maxillary sinuses and pterygomaxillary space makes this an attractive approach for large lesions in the nasal passages, nasopharynx and sphenoid sinuses.Large mucoperiosteal flaps, care to avoid the palatine vessels, and application of a palatal splint postoperatively, minimize complications and patient discomfort. The authors have used this approach to repair naso‐pharyngeal atresia, remove nasopharyngeal angiofibromas, approach the pituitary, craniopharyngioma and isolated sphenoid sinus opacification as well as sphenoid sinusitis with cavernous sinus thrombosis.
Diagnosis and management of cochlear hydrops
Authors: Glasscock III Michael E. , Miller Gale W. 
Published: October 2006

AbstractIn an early case of cochlear hydrops, the symptoms of a mild pressure sensation or fullness in the involved ear may be mistaken for a blocked eustachian tube. More severe cases demonstrate a true sensori‐neural hearing loss that fluctuates. Tinnitis is usually present during the attack and will often subside when the hearing returns to normal. The neurotologic evaluation is negative and attempts to establish an etiology are seldom fruitful. The treatment is usually medical, and empirically, these individuals are treated with diuretics, low salt diet, and vasodilators.It is felt by most investigators that cochlear hydrops is an early form of Meniere's disease, and over a long period of time these individuals may develop vertigo as a complaint.The purpose of this paper is to discuss this interesting form of Meniere's disease in detail concerning etiology, physiology, diagnosis, and treatment.A small series of patients who have undergone the subarachnoid endolymphatic sac procedure will be reported according to the guidelines set forth by the Committee on Hearing and Equilibrium of the American Academy of Ophthalmology and Otolaryngology. Based on the result in these patients, it would appear that this procedure should be considered in those individuals who are refractory to medical management. There is convincing evidence that the shunt does stabilize the hearing in many instances.
Preliminary results with use of an eustachian tube prosthesis
Authors: Wright J. William , Wright III J. William 
Published: October 2006

AbstractOne of the primary causes of tympanoplasty failure is inadequate eu‐stachian tubal function. Measures taken to improve tubal function have often been inadequate for their task. A prosthesis was constructed for the purpose of installation at the time of tympanoplasty to improve eustachian tubal function.Our early results with a two to 14‐month follow‐up of 38 patients show a success rate of 79 percent in securing an aerated middle ear space in ears which were judged to have poor eustachian tubal function.
A clinical and anatomical study of the various techniques of irrigation of the maxillary sinus
Authors: Ritter Frank N. 
Published: October 2006

AbstractIrrigation of the maxillary sinus is a common procedure in clinical practice for removing the contents of the antrum for either diagnosis or therapy. For many years, it has been accomplished by inserting a trocar in either the natural ostium or the medial wall of the sinus under the inferior turbinate.Recently, the anterior wall of the maxillary sinus has been re‐introduced as a better route. It is more direct and is the only one suited for use in a child whose sinus is underdeveloped. The anterior route has been termed the canine fossa technique and is the preferred route since it has a high degree of patient acceptance and safety and can be done easily and quickly by the clinician through a familiar anatomical pathway.
Retropharyngeal abscesses in children revisited
Authors: Seid Allan B. , Dunbar J. Scott , Cotton Robin T. 
Published: October 2006

AbstractRetropharyngeal abscess appears in infancy and early childhood. Because of the advances in antibiotic therapy, the frequency of this disease has decreased considerably. If overlooked, however, the sequelae of retropharyngeal abscess can be disastrous.Of the typical signs and symptoms listed in presentation, the swelling of the posterior pharyngeal wall is referred to as an important diagnostic sign. This presentation will discuss the fallibility of this important sign in the evaluation of a retropharyngeal abscess in children. The size of the pediatric oral cavity and the presence of pooling secretions in the pharynx, due to retropharyngeal tissue swelling, make assessment of swelling of the posterior pharyngeal wall extremely difficult.Radiological assessment of retropharyngeal abscesses cannot differentiate between cellulitis and abscess formation. The presentation will discuss the radiological appearance of a retropharyngeal swelling and discuss the differentiation of abscess formation from cellulitis.The rationale for a therapeutic regime will be developed to validate the concept that with suggestive clinical signs, suggestive radiological diagnosis, and in spite of negative evidence of retropharyngeal swelling by oral examination, justification exists for an examination under anesthesia and incision and/or aspiration of the retropharyngeal abscess.
Endoscopic lateralization of the vocal cord in abductor paralysis of the larynx
Authors: Kirchner Fernando R. 
Published: October 2006

AbstractEndoscopic surgical operations of the larynx have many desirable features, including the conservative nature of these procedures, plus the ability to produce surgical changes predictable from the onset. For several years the direct lateralization of the vocal ligament after the removal of a preassessed amount of thyroarytenoid muscle appeared to be the simplest and most accurate surgical procedure. The resection of this wedge of muscle was easily performed with laryngeal microcautery. Posterior cicatricial webs can be easily removed with this instrument. Simple suturing techniques are also described, including the practicability of using padded buttons plus lead fishing sinkers to adjust the tension and secure these sutures on the surface of the neck. So far 16 patients have been rehabilitated using this technique, including 6 patients with posterior commissure webs. These anatomical techniques should be considered because of their obvious simplicity.
The total rehabilitation of graves' ophthalmopathy
Authors: Desanto Lawrence W. 
Published: October 2006

AbstractThe concept of enlarging the orbital space in some patients with Graves' ophthalmopathy is usually acceptable. Controversial, however, are 1. the indications for enlarging the space, 2. the sequence of therapy that is most successful in restoring the eyes to near normal, and 3. the value of enlarging the orbital space and its relationship to non‐surgical alternatives.Since 1969 a personal experience with more than 600 eyes in over 300 patients using the transantral route to orbital decompression has accumulated. From the surgical experience plus exposure to other non‐surgically treated patients, a concept of total management of Graves' ophthalmopathy has evolved.The technical aspects of decompression through the sinuses are straight forward. The key to a satisfactory operation is a complete transantral ethmoidectomy; a less than complete ethmoidectomy will eliminate a predictable result.Transantral decompression as a single procedure will not successfully palliate all aspects of Graves' ophthalmopathy. Eye muscles and lid procedures in a timely sequence may be needed to complete rehabilitation. Perfect eyes are seldom obtained but the goal of satisfied patients is realistic.This essay will emphasize technical aspects, theoretical advantages, as well as pitfalls and limitations of the transantral orbital decompression.