bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virus-producing cells determine the host protein profiles of HIV-1 virion cores
Authors: Santos Steven , Obukhov Yuri , Nekhai Sergei , Bukrinsky Michael , Iordanskiy Sergey 
Published: August 2012

AbstractBackgroundUpon HIV entry into target cells, viral cores are released and rearranged into reverse transcription complexes (RTCs), which support reverse transcription and also protect and transport viral cDNA to the site of integration. RTCs are composed of viral and cellular proteins that originate from both target and producer cells, the latter entering the target cell within the viral core. However, the proteome of HIV-1 viral cores in the context of the type of producer cells has not yet been characterized.ResultsWe examined the proteomic profiles of the cores purified from HIV-1 NL4-3 virions assembled in Sup-T1 cells (T lymphocytes), PMA and vitamin D3activated THP1 (model of macrophages, mMΦ), and non-activated THP1 cells (model of monocytes, mMN) and assessed potential involvement of identified proteins in the early stages of infection using gene ontology information and data from genome-wide screens on proteins important for HIV-1 replication. We identified 202 cellular proteins incorporated in the viral cores (T cells: 125, mMΦ: 110, mMN: 90) with the overlap between these sets limited to 42 proteins. The groups of RNA binding (29), DNA binding (17), cytoskeleton (15), cytoskeleton regulation (21), chaperone (18), vesicular trafficking-associated (12) and ubiquitin-proteasome pathway-associated proteins (9) were most numerous. Cores of the virions from SupT1 cells contained twice as many RNA binding proteins as cores of THP1-derived virus, whereas cores of virions from mMΦ and mMN were enriched in components of cytoskeleton and vesicular transport machinery, most probably due to differences in virion assembly pathways between these cells. Spectra of chaperones, cytoskeletal proteins and ubiquitin-proteasome pathway components were similar between viral cores from different cell types, whereas DNA-binding and especially RNA-binding proteins were highly diverse. Western blot analysis showed that within the group of overlapping proteins, the level of incorporation of some RNA binding (RHA and HELIC2) and DNA binding proteins (MCM5 and Ku80) in the viral cores from T cells was higher than in the cores from both mMΦ and mMN and did not correlate with the abundance of these proteins in virus producing cells.ConclusionsProfiles of host proteins packaged in the cores of HIV-1 virions depend on the type of virus producing cell. The pool of proteins present in the cores of all virions is likely to contain factors important for viral functions. Incorporation ratio of certain RNA- and DNA-binding proteins suggests their more efficient, non-random packaging into virions in T cells than in mMΦ and mMN.
Single mutations in the transmembrane envelope protein abrogate the immunosuppressive property of HIV-1
Authors: Morozov Vladimir A , Morozov Alexey V , Semaan Marwan , Denner Joachim 
Published: August 2012

AbstractBackgroundThe mechanism by which HIV-1 induces AIDS is still unknown. Previously, synthetic peptides corresponding to the conserved immunosuppressive (isu) domain in gp41 of HIV-1 had been shown to inhibit proliferation and to modulate cytokine expression of immune cells. The question is, whether the viral gp41 can do the same.ResultsWe show for the first time that two trimeric forms of glycosylated gp41 released from transfected human cells modulated expression of cytokines and other genes in human PBMCs in the same manner, but at least seven hundred-fold stronger compared to that induced by the isu peptide. Single amino acid substitutions in the isu domain of gp41 introduced by site-directed mutagenesis abrogated this property. Furthermore, replication-competent HIV-1 with a mutation in the isu domain of gp41 did not modulate the cytokine expression, while wild-type virus did. Interestingly, most of the abrogating mutations were not reported in viral sequences derived from infected individuals, suggesting that mutated non-immunosuppressive viruses were eliminated by immune responses. Finally, immunisation of rats with gp41 mutated in the isu domain resulted in increased antibody responses compared with the non-mutated gp41. These results show that non-mutated gp41 is immunosuppressive in immunisation experiments, i.e.in vivo, and this has implications for the vaccine development.ConclusionsThese findings indicate that the isu domain of gp41 modulates cytokine expressionin vitroand suppresses antibody responsein vivoand therefore may contribute to the virus induced immunodeficiency.
Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy
Authors: Betancor Gilberto , Garriga César , Puertas Maria C , Nevot María , Anta Lourdes , Blanco José L , Pérez-Elías M Jesús , de Mendoza Carmen , Martínez Miguel A , Martinez-Picado Javier , Menéndez-Arias Luis ,   for the Resistance Platform of the Spanish AIDS Research Network (ResRIS)
Published: August 2012

AbstractBackgroundThymidine analogue resistance mutations (TAMs) selected under treatment with nucleoside analogues generate two distinct genotypic profiles in the HIV-1 reverse transcriptase (RT): (i) TAM1: M41L, L210W and T215Y, and (ii) TAM2: D67N, K70R and K219E/Q, and sometimes T215F. Secondary mutations, including thumb subdomain polymorphisms (e.g.R284K) have been identified in association with TAMs. We have identified mutational clusters associated with virological failure during salvage therapy with tenofovir/emtricitabine-based regimens. In this context, we have studied the role of R284K as a secondary mutation associated with mutations of the TAM1 complex.ResultsThe cross-sectional study carried out with >200 HIV-1 genotypes showed that virological failure to tenofovir/emtricitabine was strongly associated with the presence of M184V (P <10-10) and TAMs (P <10-3), while K65R was relatively uncommon in previously-treated patients failing antiretroviral therapy. Clusters of mutations were identified, and among them, the TAM1 complex showed the highest correlation coefficients. Covariation of TAM1 mutations and V118I, V179I, M184V and R284K was observed. Virological studies showed that the combination of R284K with TAM1 mutations confers a fitness advantage in the presence of zidovudine or tenofovir. Studies with recombinant HIV-1 RTs showed that when associated with TAM1 mutations, R284K had a minimal impact on zidovudine or tenofovir inhibition, and in their ability to excise the inhibitors from blocked DNA primers. However, the mutant RT M41L/L210W/T215Y/R284K showed an increased catalytic rate for nucleotide incorporation and a higher RNase H activity in comparison with WT and mutant M41L/L210W/T215Y RTs. These effects were consistent with its enhanced chain-terminated primer rescue on DNA/DNA template-primers, but not on RNA/DNA complexes, and can explain the higher fitness of HIV-1 having TAM1/R284K mutations.ConclusionsOur study shows the association of R284K and TAM1 mutations in individuals failing therapy with tenofovir/emtricitabine, and unveils a novel mechanism by which secondary mutations are selected in the context of drug-resistance mutations.
Increased cellular immune responses and CD4+ T-cell proliferation correlate with reduced plasma viral load in SIV challenged recombinant simian varicella virus - simian immunodeficiency virus (rSVV-SIV) vaccinated rhesus macaques
Authors: Pahar Bapi , Gray Wayne L , Phelps Kimberly , Didier Elizabeth S , deHaro Eileen , Marx Preston A , Traina-Dorge Vicki L 
Published: August 2012

Abstract

Background
An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV) vector – simian immunodeficiency virus (SIV) envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also significantly reduced plasma viral loads following intravenous pathogenic challenge with SIVMAC251/CX1.

Findings
The purpose of this study was to define cellular immunological correlates of protection in rSVV-SIV vaccinated and SIV challenged animals. Immunofluorescent staining and multifunctional assessment of SIV-specific T-cell responses were evaluated in both Experimental and Control vaccinated animal groups. Significant increases in the proliferating CD4+ T-cell population and polyfunctional T-cell responses were observed in all Experimental-vaccinated animals compared with the Control-vaccinated animals.

Conclusions
Increased CD4+ T-cell proliferation was significantly and inversely correlated with plasma viral load. Increased SIV-specific polyfunctional cytokine responses and increased proliferation of CD4+ T-cell may be crucial to control plasma viral loads in vaccinated and SIVMAC251/CX1 challenged macaques.
Deficits in retrospective and prospective components underlying prospective memory tasks in amnestic mild cognitive impairment
Authors: Zhou Ting , Broster Lucas S , Jiang Yang , Bao Feng , Wang Huali , Li Juan 
Published: August 2012

AbstractObjectivesBy use of purer indices of PM and RM components than previous studies and adoption of three PM task types, the present study aimed to investigate the deficits of these two components underlying global impairment at a PM task in individuals with amnestic mild cognitive impairment (aMCI).MethodsNineteen aMCI patients and 22 normal controls were examined on event-, time- and activity-based PM tasks. Separate scores were obtained for initiation of intentions (i.e. PM component) and for the content of the intentions (i.e. RM component).ResultsIndividuals with aMCI achieved lower PM component (but not RM component) scores than NCs across all three PM tasks. Furthermore, there was a trend for greater impairment on activity-based than time-based and event-based PM tasks, but which did not reach significance. In addition, a significant association between PM component and an executive function test was observed in aMCI group. PM task performance, especially activity-based PM task performance and PM component performance, successfully discriminated between aMCI and NC and was able to do so above and beyond the executive function tests.ConclusionsOur finding suggested that the deficits in PM component, related to a disrupted executive control processes, were responsible for the impaired ability of individuals with aMCI to realize delayed intentions.
Gamma Knife® radiosurgery for recurrent intracranial olfactory neuroblastoma (esthesioneuroblastoma): a case report
Authors: Dinca Eduard B , Radatz Matthias W , Rowe Jeremy , Kemeny Andras A 
Published: August 2012

Abstract

Background
We report the use of salvage radiosurgery to manage an aggressive olfactory neuroblastoma (esthesioneuroblastoma) with multiple recurrences and intracranial extension.

Case presentation
A 43-year-old Caucasian woman presented 11 years ago with progressive nasal blockage and headaches. A necrotic polyp originating in her left middle meatus and extending to the ethmoid air cells and cribriform plate (Kadish stage C) was radically resected via a craniofacial approach. Four years later, a local recurrence extending into her left cavernous sinus was identified and deemed inoperable. She received vincristine, ifosfamide, doxorubicin and etoposide chemotherapy (with minimal benefit) and external beam radiotherapy (60Gy in 30 fractions) to her skull base. Two years later, tumour extension in her left neck was treated with radical radiotherapy. She developed visual disturbances in her left eye, which progressed to blindness in the next two years. Having exhausted chemoradiotherapy, the left cavernous sinus esthesioneuroblastoma was treated with Gamma Knife® radiosurgery 2 years ago (20Gy at 50% isodose, tumour volume 7.5cm3). At one year, there was dramatic reduction in the tumour and no new symptoms; however, there were new tumour foci (in her left frontal lobe and above her right orbital apex). These were again treated with radiosurgery (20Gy at 50% isodose, total tumour volume 0.67cm3). Repeat imaging at six months showed no further disease progression.

Conclusion
Whilst rare, olfactory neuroblastoma (esthesioneuroblastoma) can present management challenges and Gamma Knife® radiosurgery may prove a useful strategy in controlling intracranial spread.
Calcified gallstone in a 3 year-old boy: a case report
Authors: Barthel Erik R , Pierce James R , Zmora Osnat , Harlan Susan R , Russell Sudha , Shin Cathy 
Published: August 2012

Abstract

Background
Gallstones are relatively rare in children. At-risk populations include patients suffering from hemolysis syndromes. Regardless of etiology, these patients usually will present with postprandial abdominal pain, and ultrasonography is the mainstay of diagnosis. However, some gallstones are radiopaque and can be visualized on plain abdominal radiography.

Case presentation
We present the uncommon but classic plain x-ray finding of a calcified gallstone in a 3 year-old Hispanic boy. He was treated with elective laparoscopic cholecystectomy.

Conclusions
Cholelithiasis is rare in children, and calcified stones that will appear on plain abdominal x-rays are even rarer. If symptomatic, cholecystectomy by a pediatric surgeon is the treatment of choice. We discuss some of the recent developments in treatment of this condition in this patient population.
Molecular characterization of thyroid hormone receptor beta from Schistosoma japonicum and assessment of its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice
Authors: Qiu Chunhui , Liu Shengfa , Hong Yang , Fu Zhiqiang , Wei Meimei , Ai Dezhou , Lin Jiaojiao 
Published: August 2012

Abstract

Background
Thyroid hormones (TH) modulate growth, development and differentiation and metabolic processes by interacting with thyroid hormone receptors (THRs). The purpose of this study was to identify a novel thyroid hormone receptor beta encoding gene of Schistosoma japonicum (SjTHRβ) and to investigate its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice.

Methods
The full-length cDNA sequence of SjTHRβ, its gene organization, and its transcript levels were characterized, and the phylogenetic relationship between THR, RAR and RXR from other organisms were analysis, the ability of this protein binding to a conserved DNA core motif, and its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice were evaluated.

Results
The SjTHRβ cDNA was cloned, verified by 5’ and 3’ Rapid Amplification of cDNA Ends and shown to be polyadenylated at the 3’end, suggesting the transcript is full-length. SjTHRβ is homologous to THRs from other species and has a predicted conservative DNA binding domain and ligand binding domain that normally characterizes these receptors. A comparative quantitative PCR analysis showed that SjTHRβ was the highest expressed in 21d worms and the lowest in 7 d and 13 d schistosomula. The cDNA corresponding to DNA binding domain (SjTHRβ-DBD) and ligand binding domain (SjTHRβ-LBD) were cloned and subsequently expressed in E coli. The expressed proteins were used to immunize mice and generate specific serum against recombinant SjTHRβ (rSjTHRβ). Western blotting revealed that anti-rSjTHRβ-LBD serum recognized two protein bands in extracts from 21 d worm with molecular sizes of approximately 95 kDa and 72 kDa. Electrophoretic mobility shift assay (EMSA) analysis showed that rSjTHRβ-DBD could bind to a conserved DNA core motif. Immunization of BALB/c mice with rSjTHRβ-LBD could induce partial protective efficacy(27.52% worm reduction and 29.50% liver eggs reduction)against schistosome infection. Enzyme-linked immunosorbent assay showed that mice vaccinated with recombinant SjTHRβ-LBD (rSjTHRβ-LBD) generated increased levels of specific IgG, IgG1 and IgG2a antibody. Bio-plex analysis demonstrated that rSjTHRβ-LBD induced considerably higher levels of T helper 1 cytokines (IL-2, IL-12 and TNF-α) than T helper 2 cytokines (IL-10, IL-4), suggesting that rSjTHRβ-LBD vaccination could stimulate mixed Th1/Th2 types with Th1 dominant immune responses.

Conclusions
Our study presented here identified SjTHRβ as a new schistosome THR that might play an important role in host-parasite interaction and be a vaccine candidate for schistosomiasis.
Acute graft versus host disease after orthotopic liver transplantation
Authors: Rogulj Inga Mandac , Deeg Joachim , Lee Stephanie J 
Published: August 2012

AbstractGraft versus host disease (GVHD) is an uncommon complication after orthotopic liver transplantation (OLT) with an incidence of 0.1–2%, but an 80–100% mortality rate. Patients can present with skin rashes, diarrhea, and bone marrow aplasia between two to eight weeks after OLT. Diagnosis of GVHD is made based on clinical and histologic evidence, supported by chimerism studies showing donor HLA alleles in the recipient bone marrow or blood. Several therapeutic approaches have been used for the management of GVHD after OLT including increased immunosuppression, decreased immunosuppression, and cellular therapies. However, success rates have been low, and new approaches are needed.
Reliability of the TekScan MatScan® system for the measurement of postural stability in older people with rheumatoid arthritis
Authors: Brenton‐Rule Angela , Mattock Joshua , Carroll Matthew , Dalbeth Nicola , Bassett Sandra , Menz Hylton B , Rome Keith 
Published: August 2012

AbstractBackgroundPostural stability can be measured in clinical and research settings using portable plantar pressure systems. People with rheumatoid arthritis (RA) have decreased postural stability compared to non‐RA populations and impaired postural stability is associated with falls in people with RA. The purpose of this study was therefore to investigate the reliability of the TekScan MatScan® system in assessing postural stability in people with RA.MethodsTwenty three participants with RA, mean (SD) age 69.74 (10.1) years, were assessed in barefoot double‐limb quiet standing, with eyes open and eyes closed, for antero‐posterior and medio‐lateral postural sway values. Three repetitions, at a sampling frequency of 40 Hz, were recorded for each test condition to obtain a mean value. Measurements were repeated one hour later. Intraclass correlation coefficients (ICC) with 95% confidence intervals (CI) were calculated to determine between‐session reliability. Measurement error was assessed through the calculation of the standard error of the measurement (SEM) and the smallest real difference (SRD).ResultsThe system displayed good to excellent reliability for antero‐posterior and medio‐lateral sway, with eyes open and closed, as indicated by ICC values ranging from 0.84 to 0.92. Measurement error, as evidenced by the SEM, ranged from 1.27 to 2.35 mm. The degree of change required to exceed the expected trial to trial variability was relatively high, compared to mean values, with SRD ranging from 3.08 to 5.71 mm.ConclusionsThe portability and ease of use of the TekScan MatScan® makes it a useful tool for the measurement of postural stability in clinical and research settings. The TekScan MatScan® system can reliably measure double‐limb quiet standing in older people, aged 60 to 80 years, with RA.
Computational analysis and predictive modeling of small molecule modulators of microRNA
Authors: Jamal Salma , Periwal Vinita , Consortium OpenSourceDrugDiscovery , Scaria Vinod 
Published: August 2012

Abstract

Background
MicroRNAs (miRNA) are small endogenously transcribed regulatory RNA which modulates gene expression at a post transcriptional level. These small RNAs have now been shown to be critical regulators in a number of biological processes in the cell including pathophysiology of diseases like cancers. The increasingly evident roles of microRNA in disease processes have also motivated attempts to target them therapeutically. Recently there has been immense interest in understanding small molecule mediated regulation of RNA, including microRNA.

Results
We have used publicly available datasets of high throughput screens on small molecules with potential to inhibit microRNA. We employed computational methods based on chemical descriptors and machine learning to create predictive computational models for biological activity of small molecules. We further used a substructure based approach to understand common substructures potentially contributing to the activity.

Conclusion
We generated computational models based on Naïve Bayes and Random Forest towards mining small RNA binding molecules from large molecular datasets. We complement this with substructure based approach to identify and understand potentially enriched substructures in the active dataset. We use this approach to identify miRNA binding potential of a set of approved drugs, suggesting a probable novel mechanism of off-target activity of these drugs. To the best of our knowledge, this is the first and most comprehensive computational analysis towards understanding RNA binding activities of small molecules and predictive modeling of these activities.
Understanding drug uptake and binding within targeted disease micro‐environments in patients: a new tool for translational medicine
Authors: Marko‐Varga György , Végvári Ákos , Rezeli Melinda , Prikk Kaiu , Ross Peeter , Dahlbäck Magnus , Edula Goutham , Sepper Ruth , Fehniger Thomas E 
Published: August 2012

AbstractBackgroundFor many common global diseases, such as cancer, diabetes, neurodegenerative and cardiovascular diseases there is an unmet need for diagnosing early indications of disease that could enable medical intervention and early treatment. The treatment of these diseases will require detailed knowledge of targeted pathways involved in disease pathogenesis but also the mode of drug actions at the biological location on these targets. Translational medicine is a new area of research where expert from different disciplines involved in basic science and clinical disciplines meet and join forces. Mode‐of‐drug‐action mechanisms elucidation is key in the characterization of drugs that can relate to both efficacy and safety.MethodsMatrix assisted laser desorption/ionization mass spectrometry imaging (MALDI‐MSI) was used providing evidence into the fate (destinations and distributions) of administered drugs within tumor regions of lung compartments.ResultsWe hereby present a pulmonary study in which we have isolated lung tissue after inhaled drug administration and then localized the drug within airway wall compartments. The histology also provides evidence of drug binding to smooth muscle cell microenvironments. We also identified lung tissue regions with tumor cell invasion in these COPD patients.ConclusionsThe ultimate goal is to identify bridging comprehension that forms a knowledge base that can be used by society to develop a better treatment and medicine for patients. Our results demonstrated that robust imaging data could be generated confirming drug localization in pulmonary regions of COPD patients with tumor pathology.Trial registrationTallinn Medical Research Ethical Committee decision #1724, 18.06.2009