bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Activation of Cellular DNA Damage Responses by Replication-Defective and Replication-Competent Adenovirus Mutants
Authors: Prakash Anand , Jayaram Sumithra , Bridge Eileen 
Published: September 2012

ABSTRACT
Adenovirus (Ad) mutants that lack early region 4 (E4) activate the phosphorylation of cellular DNA damage response proteins. In wild-type Ad type 5 (Ad5) infections, E1b and E4 proteins target the cellular DNA repair protein Mre11 for redistribution and degradation, thereby interfering with its ability to activate phosphorylation cascades important during DNA repair. The characteristics of Ad infection that activate cellular DNA repair processes are not yet well understood. We investigated the activation of DNA damage responses by a replication-defective Ad vector (AdRSVβgal) that lacks E1 and fails to produce the immediate-early E1a protein. E1a is important for activating early gene expression from the other viral early transcription units, including E4. AdRSVβgal can deliver its genome to the cell, but it is subsequently deficient for viral early gene expression and DNA replication. We studied the ability of AdRSVβgal-infected cells to induce cellular DNA damage responses. AdRSVβgal infection does activate formation of foci containing the Mdc1 protein. However, AdRSVβgal fails to activate phosphorylation of the damage response proteins Nbs1 and Chk1. We found that viral DNA replication is important for Nbs1 phosphorylation, suggesting that this step in the viral life cycle may provide an important trigger for activating at least some DNA repair proteins.
The Cellular Ataxia Telangiectasia-Mutated Kinase Promotes Epstein-Barr Virus Lytic Reactivation in Response to Multiple Different Types of Lytic Reactivation-Inducing Stimuli
Authors: Hagemeier Stacy R. , Barlow Elizabeth A. , Meng Qiao , Kenney Shannon C. 
Published: September 2012

ABSTRACTThe Epstein-Barr virus (EBV) latent-to-lytic switch is mediated by the viral proteins BZLF1 (Z), BRLF1 (R), and BRRF1 (Na). Since we previously showed that DNA-damaging agents (including chemotherapy and irradiation) can induce EBV lytic reactivation and recently demonstrated that wild-type p53 contributes to lytic reactivation, we investigated the role of the ATM kinase during EBV reactivation. ATM phosphorylates and activates p53, as well as numerous other substrates involved in the cellular DNA damage response. Using an ATM inhibitor (KU55933), we found that ATM activity is required for efficient induction of EBV lytic gene expression by a variety of different stimuli, including a histone deacetylase (HDAC) inhibitor, the transforming growth factor β (TGF-β) cytokine, a demethylating agent (5-azacytidine), B cell receptor engagement with anti-IgG antibody, hydrogen peroxide, and the proteosome inhibitor bortezomib. In EBV-infected AGS (gastric) cells, knockdown of ATM, or p53, expression inhibits EBV reactivation. Conversely, treatment of these cells with nutlin-3 (which activates p53 and ATM) robustly induces lytic reactivation in a p53- and ATM-dependent manner. The ability of the EBV R and Na proteins to induce lytic reactivation in EBV-infected AGS cells is ATM dependent. However, overexpression of Z induces lytic gene expression in the presence or absence of ATM activity. Our results suggest that ATM enhances Z promoter activity in the context of the intact EBV genome and that p53 contributes to the ATM effect. Nevertheless, since we found that ATM inhibitors also reduce lytic reactivation in Burkitt lymphoma cells that have no p53, additional ATM substrates must also contribute to the ATM effect.
Comprehensive Analysis of Host Cellular Interactions with Human Papillomavirus E6 Proteins Identifies New E6 Binding Partners and Reflects Viral Diversity
Authors: White Elizabeth A. , Kramer Rebecca E. , Tan Min Jie Alvin , Hayes Sebastian D. , Harper J. Wade , Howley Peter M. 
Published: September 2012

ABSTRACT
We have begun to define the human papillomavirus (HPV)-associated proteome for a subset of the more than 120 HPV types that have been identified to date. Our approach uses a mass spectrometry-based platform for the systematic identification of interactions between human papillomavirus and host cellular proteins, and here we report a proteomic analysis of the E6 proteins from 16 different HPV types. The viruses included represent high-risk, low-risk, and non-cancer-associated types from genus alpha as well as viruses from four different species in genus beta. The E6 interaction data set consists of 153 cellular proteins, including several previously reported HPV E6 interactors such as p53, E6AP, MAML1, and p300/CBP and proteins containing PDZ domains. We report the genus-specific binding of E6s to either E6AP or MAML1, define the specific HPV E6s that bind to p300, and demonstrate several new features of interactions involving beta HPV E6s. In particular, we report that several beta HPV E6s bind to proteins containing PDZ domains and that at least two beta HPV E6s bind to p53. Finally, we report the newly discovered interaction of proteins of E6 of beta genus, species 2, with the Ccr4-Not complex, the first report of a viral protein binding to this complex. This data set represents a comprehensive survey of E6 binding partners that provides a resource for the HPV field and will allow continued studies on the diverse biology of the human papillomaviruses.
Mental health effects from urban bed bug infestation (Cimex lectulariusL.): a cross-sectional study
Authors: Susser Stephanie Rebecca , Perron Stéphane , Fournier Michel , Jacques Louis , Denis Geoffroy , Tessier François , Roberge Pasquale 
Published: September 2012

ObjectiveTo assess whether bed bug infestation was linked to sleep disturbances and symptoms of anxiety and depression.DesignExploratory cross-sectional study.SettingConvenience sample of tenants recruited in apartment complexes from Montreal, Canada.Participants39 bed bug-exposed tenants were compared with 52 unexposed tenants.Main outcome measuresThe effect of bed bug-exposed tenants on sleep disturbances, anxiety and depression symptoms measured using the Pittsburgh Sleep Quality Index, 5th subscale, Generalised Anxiety Disorder 7-item scale and Patient Health Questionnaire, 9-item, respectively.ResultsIn adjusted models, bed bug infestation was strongly associated with measured anxiety symptoms (OR (95% CI)=4.8 (1.5 to 14.7)) and sleep disturbance (OR (95% CI)=5.0 (1.3–18.8)). There was a trend to report more symptoms of depression in the bed bug-infested group, although this finding was not statistically significant ((OR (95% CI)=2.5(0.8 to 7.3)).ConclusionsThese results suggest that individuals exposed to bed bug infestations are at risk of experiencing sleep disturbance and of developing symptoms of anxiety and possibly depression. Greater clinical awareness of this problem is needed in order for patients to receive appropriate mental healthcare. These findings highlight the need for undertaking of deeper inquiry, as well as greater collaboration between medical professionals, public health and community stakeholders.
Method for developing national quality indicators based on manual data extraction from medical records
Authors: Couralet Melanie , Leleu Henri , Capuano Frederic , Marcotte Leah , Nitenberg Gérard , Sicotte Claude , Minvielle Etienne 
Published: September 2012

Developing quality indicators (QI) for national purposes (eg, public disclosure, paying-for-performance) highlights the need to find accessible and reliable data sources for collecting standardised data. The most accurate and reliable data source for collecting clinical and organisational information still remains the medical record. Data collection from electronic medical records (EMR) would be far less burdensome than from paper medical records (PMR). However, the development of EMRs is costly and has suffered from low rates of adoption and barriers of usability even in developed countries. Currently, methods for producing national QIs based on the medical record rely on manual extraction from PMRs.We propose and illustrate such a method. These QIs display feasibility, reliability and discriminative power, and can be used to compare hospitals. They have been implemented nationwide in France since 2006. The method used to develop these QIs could be adapted for use in large-scale programmes of hospital regulation in other, including developing, countries.
Who would use PrEP? Factors associated with intention to use among MSM in London: a community survey
Authors: Aghaizu Adamma , Mercey Danielle , Copas Andrew , Johnson Anne M , Hart Graham , Nardone Anthony 
Published: September 2012

ObjectiveTo assess current and intended future use of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) and characterise those attending sexual health clinics, the anticipated PrEP delivery setting.DesignCross-sectional study.MethodsSelf-administered survey of 842 HIV negative MSM recruited from social venues in London in 2011.ResultsOne in 10 (10.2%, 83/814, 95% CI 8.2% to 12.5%) and one in 50 (2.1%, 17/809, 95% CI 1.2% to 3.3%) reported having ever used post-exposure prophylaxis (PEP) and PrEP respectively. Half reported they would be likely to use PrEP if it became available as a daily pill (50.3%, 386/786, 95% CI 46.7% to 53.9%). MSM were more likely to consider future PrEP use if they were <35 years (adjusted OR (AOR) 1.57, 95% CI 1.16 to 2.14), had unprotected anal intercourse with casual partners (AOR 1.70, 95% CI 1.13 to 2.56), and had previously used PEP (AOR 1.94, 95% CI 1.17 to 3.24). Over half of MSM (54.8% 457/834 95% CI 51.3 to 58.2) attended a sexual health clinic the previous year. Independent factors associated with attendance were age <35 (AOR 2.29, 95% CI 1.68 to 3.13), and ≥10 anal sex partners in the last year (AOR 2.49, 95% CI 1.77 to 3.52).ConclusionsThe concept of PrEP for HIV prevention in the form of a daily pill is acceptable to half of sexually active MSM in London. MSM reporting higher risk behaviours attend sexual health clinics suggesting this is a suitable setting for PrEP delivery.
Submucosal Lingualplasty for Adult Obstructive Sleep Apnea
Authors: Gunawardena Indunil , Robinson Sam , MacKay Stuart , Woods Charmaine M. , Choo June , Esterman Adrian , Carney A. Simon 
Published: September 2012

ObjectiveTo measure quality‐of‐life outcomes, polysomnographic outcomes, and adverse effects for a new technique of tongue reduction in obstructive sleep apnea.Study DesignCase series.SettingTertiary hospital.Subjects and MethodsConsecutively treated adult patients (N = 27) with obstructive sleep apnea having submucosal lingualplasty in 2007 were studied. All had concurrent or previous uvulopalatoplasty ± palatal advancement. Full polysomnography preoperatively and 3.7 ± 0.4 months postoperatively, scored using the American Academy of Sleep Medicine 2007 criteria, was recorded. Snoring severity score, Epworth Sleepiness Scale, and complication data were collected at a 2.61 ± 0.08‐year follow‐up via questionnaire.ResultsMean snoring severity score fell from 7.1 ± 0.4 to 2.3 ± 0.6 (P <. 05). Epworth Sleepiness Scale score fell from 8.3 ± 1.1 to 5.8 ± 1.0 (P <. 05). The apnea‐hypopnea index (AHI) fell from 44.0 ± 4.3 to 12.5 ± 2.3 (P <. 05). Success, defined as achieving an AHI <15 postoperatively, was observed in 74% (20/27), with each of these patients achieving a reduction in AHI >50%. Lowest oxygen saturation improved from 84 ± 1 to 88 ± 1 (P <. 05). Pain was mild to moderate. Short‐term postoperative complications included bleeding (3.7%) and infection (14.8%). Some minor long‐term (6 months) alteration in tongue function was reported with regard to speech (47%), swallow (33%), and taste (33%).ConclusionSubmucosal lingualplasty with concurrent palatal surgery is a promising treatment option in adult patients with obstructive sleep apnea with macroglossia.
Transnasal Endoscopic Repair of Posterior Table Fractures
Authors: Chaaban Mohamad R. , Conger Bryant , Riley Kristen O. , Woodworth Bradford A. 
Published: September 2012

Objectives/HypothesisConventional treatment of frontal sinus posterior table fractures has included osteoplastic flap or cranialization procedures despite considerable advances in endoscopic technique and experience. The objective of the current study was to evaluate outcomes of frontal sinus fractures involving the posterior table managed using endoscopic approaches.Study DesignProspective cohort.SettingTertiary care, academic university hospital.MethodsProspective evaluation of patients with posterior table fractures was performed. Data were collected regarding demographics, etiology, technique, operative site, length involving the posterior table, size of the skull base defect, complications, and clinical follow‐up.ResultsThirteen patients (average age 37 years) with posterior table fractures were treated using endoscopic techniques from 2008 to 2012. Mean follow‐up time was 68 weeks (range, 2‐206 weeks). Patients were primarily managed using Draf IIb frontal sinusotomies with 1 individual requiring a concomitant trephine. A Draf III procedure was performed in 1 patient. Average fracture defect (length vs width) was 13 × 4.5 mm, and average length involving the posterior table was 9.7 mm (1‐30 mm). Skull base defects were covered with a septal flap and/or free tissue grafts. Although 1 individual required a revision frontal sinusotomy and follow‐up was short in several patients, all sinuses remained patent on last clinical examination.ConclusionManagement of frontal sinus posterior table fractures using minimally invasive endoscopic techniques provides excellent outcomes in selected cases. Fractures of up to 30 mm in length were adequately managed in this series and indicate this approach can be a viable alternative in the treatment of these fractures.
DNA damage in human skin keratinocytes caused by multiwalled carbon nanotubes with carboxylate functionalization
Authors: McShan Danielle , Yu Hongtao 
Published: September 2012

Water-soluble carbon nanotubes have been found to be one of the most promising nanomaterials in biological- and biomedical-based applications. However, there have been major concerns on their ability to cause cellular and DNA damages upon exposure. In this work, we explore the toxic effects of three multiwalled carbon nanotubes (MWCNTs: nonpurified, purified and carboxylate-functionalized) on human skin keratinocytes (HaCaT). Cytotoxicity tests using the conventional thiazolyl blue tetrazolium bromide (MTT) and the water-soluble tetrazolium (WST-1) assays for 0.5 or 24 h exposure to 20 μg/mL of MWCNTs show that all three caused minimum cytotoxicity that is generally not statistically significant. Assessment of direct and oxidative DNA damages using both alkaline Comet assay and formamidopyrimidine DNA glycosylase-modified Comet assay reveals that the treatment with 20 μg/mL of MWCNTs does not cause significant direct DNA damages, but causes great amount of oxidative DNA damages in HaCaT cells. The oxidative DNA damage reaches the maximum amount at 4 h of incubation in Dulbecco’s minimum essential medium, but decreases to the minimum at 8 and 24 h of incubation, indicating repair of the oxidative damages by the intrinsic DNA repair mechanism of the cells.
Witchcraft and Huntington’s disease: a salutary history of societal and medical stigmatisation
Authors: Loi Samantha , Chiu Edmond 
Published: September 2012

Objective: This paper examines the notions that psychiatry can be greatly influenced by what society considers as ‘normal’, and that psychiatric thoughts and beliefs ebb and flow according to history and the social and cultural values of the time. Conclusions: As part of the medical profession, psychiatrists have much power in determining treatment and outcomes for patients. Unfortunately, this also means psychiatry has also been involved with the darker aspects of humanity, such as during the Nazi regime, and the abuse of patients’ human rights. Huntington’s disease (HD) is a neuropsychiatric illness from which observation and little knowledge reported by the medical profession spanned decades of incorrect and sensationalised documentation, that was also influenced by the values of the time. Such was the atmosphere of society during this period that the ideas and notions regarding HD disseminated by the respected medical profession were believed and accepted as fact by the general population and other professions, who would have been ignorant of any other contrary information. We need to be aware of social and cultural values as these can influence our understanding of diagnoses and treatments of our patients.
Leg Pain and Gynecologic Malignancy
Authors: Singh Lilly , Stevens Erin E. 
Published: September 2012

Gynecologic malignancies affect more than 83 000 women in the United States, each year. Because the disease involves the pelvis, many patients have side effects distal to this area in their lower extremities. The differential diagnosis of leg pain can be divided into vascular, neurologic, and musculoskeletal causes. In this review article, we address numerous etiologies of leg pain, reviewing the prevalence of disease, physical examination findings, diagnostic as well as treatment modalities.
Genistein inhibits cell invasion and motility by inducing cell differentiation in murine osteosarcoma cell line LM8
Authors: Nakamura Atsushi , Aizawa Junichi , Sakayama Kenshi , Kidani Teruki , Takata Tomoyo , Norimatsu Yoshiaki , Miura Hiromasa , Masuno Hiroshi 
Published: September 2012

Abstract

Background
One of the problems associated with osteosarcoma is the frequent formation of micrometastases in the lung prior to diagnosis because the development of metastatic lesions often causes a fatal outcome. Therefore, the prevention of pulmonary metastases during the early stage of tumor development is critical for the improvement of the prognosis of osteosarcoma patients. In Japan, soy is consumed in a wide variety of forms, such as miso soup and soy sauce. The purpose of this study is to investigate the effect of genistein, an isoflavone found in soy, on the invasive and motile potential of osteosarcoma cells.

Methods
LM8 cells were treated for 3 days with various concentrations of genistein. The effect of genistein on cell proliferation was determined by DNA measurement in the cultures and 5-bromo-2’-deoxyuridine (BrdU) incorporation study. The assays of cell invasion and motility were performed using the cell culture inserts with either matrigel-coated membranes or uncoated membranes in the invasion chambers. The expression and secretion of MMP-2 were determined by immunohistochemistry and gelatin zymography. The subcellular localization and cellular level of β-catenin were determined by immunofluorescence and Western blot. For examining cell morphology, the ethanol-fixed cells were stained with hematoxylin-eosin (H&E). The expression of osteocalcin mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR).

Results
Genistein dose-dependently inhibits cell proliferation. Genistein-treated cells were less invasive and less motile than untreated cells. The expression and secretion of MMP-2 were lower in the genistein-treated cultures than in the untreated cultures. β-Catenin in untreated cells was located in the cytoplasm and/or nucleus, while in genistein-treated cells it was translocated near to the plasma membrane. The level of β-catenin was higher in genistein-treated cells than in untreated cells. Treatment of LM8 cells with genistein induced morphological changes, markedly decreased the formation of multilayer masses of cells, and markedly increased the expression of osteocalcin mRNA.

Conclusions
Genistein decreased invasive and motile potential by inducing cell differentiation in LM8 cells. Genistein may be useful as an anti-metastatic drug for osteosarcoma through its differentiation-inducing effects.
Is the C-terminal insertional signal in Gram-negative bacterial outer membrane proteins species-specific or not?
Authors: Paramasivam Nagarajan , Habeck Michael , Linke Dirk 
Published: September 2012

AbstractBackgroundIn Gram-negative bacteria, the outer membrane is composed of an asymmetric lipid bilayer of phopspholipids and lipopolysaccharides, and the transmembrane proteins that reside in this membrane are almost exclusively β-barrel proteins. These proteins are inserted into the membrane by a highly conserved and essential machinery, the BAM complex. It recognizes its substrates, unfolded outer membrane proteins (OMPs), through a C-terminal motif that has been speculated to be species-specific, based on theoretical and experimental results from only two species,Escherichia coliandNeisseria meningitidis, where it was shown on the basis of individual sequences and motifs that OMPs from the one cannot easily be over expressed in the other, unless the C-terminal motif was adapted. In order to determine whether this species specificity is a general phenomenon, we undertook a large-scale bioinformatics study on all predicted OMPs from 437 fully sequenced proteobacterial strains.ResultsWe were able to verify the incompatibility reported betweenEscherichia coliandNeisseria meningitidis, using clustering techniques based on the pairwise Hellinger distance between sequence spaces for the C-terminal motifs of individual organisms. We noticed that the amino acid position reported to be responsible for this incompatibility betweenEscherichia coliandNeisseria meningitidisdoes not play a major role for determining species specificity of OMP recognition by the BAM complex. Instead, we found that the signal is more diffuse, and that for most organism pairs, the difference between the signals is hard to detect. Notable exceptions are theNeisseriales, andHelicobacter spp. For both of these organism groups, we describe the specific sequence requirements that are at the basis of the observed difference.ConclusionsBased on the finding that the differences between the recognition motifs of almost all organisms are small, we assume that heterologous overexpression of almost all OMPs should be feasible inE. coliand other Gram-negative bacterial model organisms. This is relevant especially for biotechnology applications, where recombinant OMPs are used e.g. for the development of vaccines. For the species in which the motif is significantly different, we identify the residues mainly responsible for this difference that can now be changed in heterologous expression experiments to yield functional proteins.