bluuebunny/crossref_metadata_2025_split huggingface dataset:
JC Virus-Induced Changes in Cellular Gene Expression in Primary Human Astrocytes
Authors: Radhakrishnan Sujatha , Otte Jessica , Enam Sahnila , Del Valle Luis , Khalili Kamel , Gordon Jennifer 
Published: September 2003

ABSTRACT
Cell-type-specific transcription of the JC virus (JCV) promoter in glial cells initiates a series of events leading to viral replication in the brain and the development of the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) in patients with neurologic complications due to infection with human immunodeficiency virus type 1. Here we employed an in vitro infection of primary cultures of human astrocytes to compare the transcriptional profile of cellular genes after JCV infection by using an oligonucleotide-based microarray of 12,600 genes. Transcription of nearly 355 genes was enhanced and expression of 130 genes was decreased to various degrees. Many transcripts that were increased upon JCV infection were found to encode proteins with properties that suggest their involvement in cell proliferation, including cyclin A and cyclin B1; signaling pathways, such as transforming growth factor β receptor 1, platelet-derived growth factor receptor and fibroblast growth factor family receptor; and other regulatory events, such as inflammatory responses, including cyclo-oxygenase-2 (Cox-2). Microarray-based data for several cell cycle-regulatory genes were further examined by using Western blot analysis of in vitro infected astrocytes harvested early and late during the infection. Results demonstrate that protein levels of all upregulated genes were found to increase at some point during the infection time course. In parallel, immunohistochemical assessment of cell cycle proteins, including cyclins A, B1, E, and Cdk2, showed positive staining of astrocytes within PML lesions of brain tissue from patients with neuro-AIDS. Microarray analysis was found to be a useful predictor of gene expression in infected cells; however, it may not directly correlate with protein levels during infection with JCV.
Preinfection Treatment of Resistant Mice with CpG Oligodeoxynucleotides Renders Them Susceptible to Friend Retrovirus-Induced Leukemia
Authors: Olbrich Anke R. M. , Schimmer Simone , Dittmer Ulf 
Published: September 2003

ABSTRACTWe recently reported that immunostimulatory oligodeoxynucleotides (CpG oligodeoxynucleotides [CpG-ODN]) were effective in postexposure treatment of retrovirus-induced disease (A. R. M. Olbrich et al., J. Virol. 76:11397-11404, 2002). We now show that the timing of treatment is a critical factor in treatment efficacy. In stark contrast to the success of postexposure treatments, we found that CpG treatment of susceptible mice prior to Friend retrovirus infection accelerated the development of virus-induced erythroleukemia. Furthermore, 70.8% of mice that were resistant to Friend virus-induced leukemia developed disease after inoculation of CpG-ODN before infection. The CpG pretreatment of these mice enhanced viral loads in their spleens and blood compared to controls that received ODN without CpG motifs. The main target cells of Friend virus, erythroid precursor cells and B cells, proliferated after CpG-ODN inoculation and provided an enlarged target cell population for viral infection. Our present findings together with our previous report demonstrate that CpG-ODN treatment of viral infections may be a double-edged sword that can result in an effective therapy but also in an acceleration of disease progression depending on the time point of treatment.
Interaction between Human Respiratory Syncytial Virus (RSV) M2-1 and P Proteins Is Required for Reconstitution of M2-1-Dependent RSV Minigenome Activity
Authors: Mason Stephen W. , Aberg Erika , Lawetz Carol , DeLong Rachel , Whitehead Paul , Liuzzi Michel 
Published: September 2003

ABSTRACT
We have investigated protein-protein interactions among the respiratory syncytial virus (RSV) RNA polymerase subunits using affinity chromatography. Here we demonstrate a novel interaction of P and M2-1 proteins. Phosphorylation of either M2-1 or P appears to be dispensable for this interaction. Internal deletions within P mapped the M2-1-binding domain to a region between residues 100 and 120. Alanine-scanning mutagenesis within this region of P revealed that substitution of any one of the three residues, L101, Y102, and F109, prevented both M2-1 and P binding and expression of an M2-1-dependent luciferase reporter gene. However, these same mutations did not prevent the activity of an M2-1-independent chloramphenicol acetyltransferase minigenome, suggesting that these residues of P specifically affect M2-1-P interaction. On the basis of these observations, it is possible that the interaction between RSV M2-1 and P proteins is important for viral replication.
Development and Use of a Vaccinia Virus Neutralization Assay Based on Flow Cytometric Detection of Green Fluorescent Protein
Authors: Earl Patricia L. , Americo Jeffrey L. , Moss Bernard 
Published: September 2003

ABSTRACT
A rapid and sensitive neutralization assay is required to evaluate alternative smallpox vaccines. Here we describe the development and use of a 96-well plate, semi-automated, flow cytometric assay that uses a recombinant vaccinia virus expressing enhanced green fluorescent protein and which would be applicable to other viruses.
Novel Simian Homologues of Epstein-Barr Virus
Authors: Ehlers Bernhard , Ochs Andreas , Leendertz Fabian , Goltz Michael , Boesch Christophe , Mätz-Rensing Kerstin 
Published: September 2003

ABSTRACT

Thirty different lymphocryptoviruses (LCV), 26 of them novel, were detected in primates by a panherpesvirus PCR assay. Nineteen LCV from chimpanzees, bonobos, gorillas, and other Old World primates were closely related to Epstein-Barr virus (EBV), the type species of the genus
Lymphocryptovirus
. Seven LCV originating from New World primates were related to callitrichine herpesvirus 3 (CalHV-3), the first recognized New World LCV. Importantly, a second LCV from gorillas and three LCV from orangutans and gibbons were only distantly related to EBV and CalHV-3. They were tentatively assigned to a novel genogroup of Old World primate LCV. The work described in the paper may also help identify an as yet unknown human LCV.
Simian Virus 40 T Antigens and J Domains: Analysis of Hsp40 Cochaperone Functions in
Escherichia coli
Authors: Genevaux Pierre , Lang Florence , Schwager Françoise , Vartikar Jai V. , Rundell Kathleen , Pipas James M. , Georgopoulos Costa , Kelley William L. 
Published: September 2003

ABSTRACT

The N-terminal exon of DNA tumor virus T antigens represents a J domain that can direct interaction with the host-encoded Hsp70 chaperones. We have taken advantage of rapid Hsp40 cochaperone assays with
Escherichia coli
to assess simian virus 40 (SV40)-encoded J-domain loss of function. We found a strong correlation between loss of cochaperone function in
E. coli
and defective SV40 growth, suggesting that the major role of the J domain in DNA tumor viruses is to provide cochaperone function. We also report the expression of native SV40 virus T antigens in
E. coli
. Our results show that small t antigen, but not large T antigen (LT) or LT truncation TN125 or TN136, can functionally replace under limited growth conditions DnaJ (Hsp40) function in vivo. In addition, purified small t antigen can efficiently stimulate
E. coli
DnaK's (Hsp70) ATPase in vitro, thus behaving like a bona fide cochaperone. Furthermore, small t amino acids 83 to 174, which are adjacent to the viral J domain, can replace the
E. coli
DnaJ J-domain glycine-phenylalanine-rich domain, immediately adjacent to the J-domain sequences, even in the absence of significant amino acid similarity to their DnaJ counterpart. Taken together, our studies demonstrate that functionally related Hsp40 proteins from mammalian viral systems can be rapidly studied in bacteria and exploited to probe the universally conserved Hsp70 chaperone machine mechanism.
The Gene That Encodes the Herpes Simplex Virus Type 1 Latency-Associated Transcript Influences the Accumulation of Transcripts (Bcl-x
L
and Bcl-x
S
) That Encode Apoptotic Regulatory Proteins
Authors: Peng Weiping , Henderson Gail , Perng Guey-Chuen , Nesburn Anthony B. , Wechsler Steven L. , Jones Clinton 
Published: September 2003

ABSTRACT

The herpes simplex virus type 1 latency-associated transcript (LAT) inhibits apoptosis. We demonstrate here that LAT influences the accumulation of the Bcl-x
L
transcript versus the Bcl-x
S
transcript in Neuro-2A cells. Bcl-x
L
encodes an antiapoptotic protein, whereas Bcl-x
S
encodes a proapoptotic protein. Promoting the accumulation of Bcl-x
L
in neurons may inhibit apoptosis, thus enhancing the latency-reactivation cycle.
Detection of a Gene Cluster That Is Dispensable for Human Herpesvirus 6 Replication and Latency
Authors: Kondo Kazuhiro , Nozaki Hideo , Shimada Kazuya , Yamanishi Koichi 
Published: September 2003

ABSTRACT
The U3-U7 gene cluster of human herpesvirus 6 (HHV-6) was replaced with an enhanced green fluorescent protein-puromycin gene cassette containing the cytomegalovirus major immediate-early promoter. Neither viral replication in T cells nor latency and reactivation in macrophages was impaired. During HHV-6 latency, the cytomegalovirus promoter used the transcription start sites employed in cytomegalovirus latency.
A Lipase Isolated from the Silkworm
Bombyx mori
Shows Antiviral Activity against Nucleopolyhedrovirus
Authors: Ponnuvel Kangayam M. , Nakazawa Hiroshi , Furukawa Seiichi , Asaoka Ai , Ishibashi Jun , Tanaka Hiromitsu , Yamakawa Minoru 
Published: September 2003

ABSTRACT

A protein showing strong antiviral activity against
Bombyx mori
nucleopolyhedrovirus (BmNPV) was purified from the digestive juice of
B. mori
larvae. A homology search of the deduced amino acid sequence of the protein cDNA revealed 56% homology with
Drosophila melanogaster
lipase and 21% homology with human lipase. As lipase activity of the protein was confirmed in vitro, this protein was designated Bmlipase-1. Northern blot analysis showed that the Bmlipase-1 gene is expressed in the midgut but not in other tissues, nor is it activated by BmNPV infection. In addition, the Bmlipase-1 gene was shown not to be expressed in the molting and wandering stages, indicating that the gene is hormonally regulated. Our results suggest that an insect digestive enzyme has potential as a physiological barrier against BmNPV at the initial site of viral infection.
Life and Perceptual Intentionality
Authors: Barbaras Renaud 
Published: September 2003

AbstractHusserl is the first philosopher who has managed to account for the specificity of perception, characterized as givenness by sketches (Abschattungen); but neither Husserl nor Merleau-Ponty have given a satisfying definition of the subject of perception. This article tries to show that the subject of perception must be conceived as living being and that, therefore, the phenomenology of perception must lead to a phenomenology of life. Here, life is approached from an existential point of view, that is to say, as a specific relationship to the world. However, life cannot be characterized from human existence in a privative way, as in Heidegger's philosophy: on the contrary, human existence, and particularly perception itself, must be understood from vital existence, and accordingly, an "additive" anthropology must replace the privative zoology. The hypothesis of this article is that it is by characterizing life as desire, we are able to account for perception as givenness by sketches.
Prescription Stimulant Use During Pregnancy and Risk of Neurodevelopmental Disorders in Children
Authors: Suarez Elizabeth A. , Bateman Brian T. , Hernandez-Diaz Sonia , Straub Loreen , McDougle Christopher J. , Wisner Katherine L. , Gray Kathryn J. , Pennell Page B. , Lester Barry , Zhu Yanmin , Mogun Helen , Huybrechts Krista F. 
Published: January 2024

ImportanceUse of medications for attention-deficit/hyperactivity disorder (ADHD) during pregnancy is increasing in the US. Whether exposure to these medications in utero impacts the risk of neurodevelopmental disorders in children is uncertain.ObjectiveTo evaluate the association of childhood neurodevelopmental disorders with in utero exposure to stimulant medications for ADHD.Design, Setting, and ParticipantsThis cohort study included health care utilization data from publicly insured (Medicaid data from 2000 to 2018) and commercially insured (MarketScan Commercial Claims Database data from 2003 to 2020) pregnant individuals aged 12 to 55 years in the US with enrollment from 3 months prior to pregnancy through 1 month after delivery, linked to children. Children were monitored from birth until outcome diagnosis, disenrollment, death, or end of the study (December 2018 for Medicaid and December 2020 for MarketScan).ExposuresDispensing of amphetamine/dextroamphetamine or methylphenidate in the second half of pregnancy.Main Outcomes and MeasuresAutism spectrum disorder, ADHD, and a composite of any neurodevelopmental disorder were defined using validated algorithms. Hazard ratios were estimated comparing amphetamine/dextroamphetamine and methylphenidate to no exposure.ResultsThe publicly insured cohort included 2 496 771 stimulant-unexposed, 4693 amphetamine/dextroamphetamine-exposed, and 786 methylphenidate-exposed pregnancies with a mean (SD) age of 25.2 (6.0) years. The commercially insured cohort included 1 773 501 stimulant-unexposed, 2372 amphetamine/dextroamphetamine-exposed, and 337 methylphenidate-exposed pregnancies with a mean (SD) age of 31.6 (4.6) years. In unadjusted analyses, amphetamine/dextroamphetamine and methylphenidate exposure were associated with a 2- to 3-fold increased risk of the neurodevelopmental outcomes considered. After adjustment for measured confounders, amphetamine/dextroamphetamine exposure was not associated with any outcome (autism spectrum disorder: hazard ratio [HR], 0.80; 95% CI, 0.56-1.14]; ADHD: HR, 1.07; 95% CI, 0.89-1.28; any neurodevelopmental disorder: HR, 0.91; 95% CI, 0.81-1.28). Methylphenidate exposure was associated with an increased risk of ADHD (HR, 1.43; 95% CI, 1.12-1.82]) but not other outcomes after adjustment (autism spectrum disorder: HR, 1.06; 95% CI, 0.62-1.81; any neurodevelopmental disorder: HR, 1.15; 95% CI, 0.97-1.36). The association between methylphenidate and ADHD did not persist in sensitivity analyses with stricter control for confounding by maternal ADHD.Conclusions and RelevanceThe findings in this study suggest that amphetamine/dextroamphetamine and methylphenidate exposure in utero are not likely to meaningfully increase the risk of childhood neurodevelopmental disorders.
Gross failure rates and failure modes for a commercial AI‐based auto‐segmentation algorithm in head and neck cancer patients
Authors: Temple Simon W. P. , Rowbottom Carl G. 
Published: January 2024

AbstractPurposeArtificial intelligence (AI) based commercial software can be used to automatically delineate organs at risk (OAR), with potential for efficiency savings in the radiotherapy treatment planning pathway, and reduction of inter‐ and intra‐observer variability. There has been little research investigating gross failure rates and failure modes of such systems.Method50 head and neck (H&N) patient data sets with “gold standard” contours were compared to AI‐generated contours to produce expected mean and standard deviation values for the Dice Similarity Coefficient (DSC), for four common H&N OARs (brainstem, mandible, left and right parotid). An AI‐based commercial system was applied to 500 H&N patients. AI‐generated contours were compared to manual contours, outlined by an expert human, and a gross failure was set at three standard deviations below the expected mean DSC. Failures were inspected to assess reason for failure of the AI‐based system with failures relating to suboptimal manual contouring censored. True failures were classified into 4 sub‐types (setup position, anatomy, image artefacts and unknown).ResultsThere were 24 true failures of the AI‐based commercial software, a gross failure rate of 1.2%. Fifteen failures were due to patient anatomy, four were due to dental image artefacts, three were due to patient position and two were unknown. True failure rates by OAR were 0.4% (brainstem), 2.2% (mandible), 1.4% (left parotid) and 0.8% (right parotid).ConclusionTrue failures of the AI‐based system were predominantly associated with a non‐standard element within the CT scan. It is likely that these non‐standard elements were the reason for the gross failure, and suggests that patient datasets used to train the AI model did not contain sufficient heterogeneity of data. Regardless of the reasons for failure, the true failure rate for the AI‐based system in the H&N region for the OARs investigated was low (∼1%).
Tau maturation in the clinicopathological spectrum of Lewy body and Alzheimer's disease
Authors: Arezoumandan Sanaz , Cousins Katheryn A.Q. , Ohm Daniel T. , Lowe MaKayla , Chen Min , Gee James , Phillips Jeffrey S. , McMillan Corey T. , Luk Kelvin C. , Deik Andres , Spindler Meredith A. , Tropea Thomas F. , Weintraub Daniel , Wolk David A. , Grossman Murray , Lee Virginia , Chen‐Plotkin Alice S. , Lee Edward B. , Irwin David J. 
Published: January 2024

AbstractObjectiveAlzheimer's disease neuropathologic change and alpha‐synucleinopathy commonly co‐exist and contribute to the clinical heterogeneity of dementia. Here, we examined tau epitopes marking various stages of tangle maturation to test the hypotheses that tau maturation is more strongly associated with beta‐amyloid compared to alpha‐synuclein, and within the context of mixed pathology, mature tau is linked to Alzheimer's disease clinical phenotype and negatively associated with Lewy body dementia.MethodsWe used digital histology to measure percent area‐occupied by pathology in cortical regions among individuals with pure Alzheimer's disease neuropathologic change, pure alpha‐synucleinopathy, and a co‐pathology group with both Alzheimer's and alpha‐synuclein pathologic diagnoses. Multiple tau monoclonal antibodies were used to detect early (AT8, MC1) and mature (TauC3) epitopes of tangle progression. We used linear/logistic regression to compare groups and test the association between pathologies and clinical features.ResultsThere were lower levels of tau pathology (β = 1.86–2.96, p < 0.001) across all tau antibodies in the co‐pathology group compared to the pure Alzheimer's pathology group. Among individuals with alpha‐synucleinopathy, higher alpha‐synuclein was associated with greater early tau (AT8 β = 1.37, p < 0.001; MC1 β = 1.2, p < 0.001) but not mature tau (TauC3 p = 0.18), whereas mature tau was associated with beta‐amyloid (β = 0.21, p = 0.01). Finally, lower tau, particularly TauC3 pathology, was associated with lower frequency of both core clinical features and categorical clinical diagnosis of dementia with Lewy bodies.InterpretationMature tau may be more closely related to beta‐amyloidosis than alpha‐synucleinopathy, and pathophysiological processes of tangle maturation may influence the clinical features of dementia in mixed Lewy‐Alzheimer's pathology.
Combined Orbital and Cranial Vessel Wall Magnetic Resonance Imaging for the Assessment of Disease Activity in Giant Cell Arteritis
Authors: Rhee Rennie L. , Rebello Ryan , Tamhankar Madhura A. , Banerjee Shubhasree , Liu Fang , Cao Quy , Kurtz Robert , Baker Joshua F. , Fan Zhaoyang , Bhatt Vatsal , Amudala Naomi , Chou Sherry , Liang Rui , Sanchez Marisa , Burke Morgan , Desiderio Lisa , Loevner Laurie A. , Morris Jeffrey S. , Merkel Peter A. , Song Jae W. 
Published: January 2024

ObjectiveAcute visual impairment is the most feared complication of giant cell arteritis (GCA) but is challenging to predict. Magnetic resonance imaging (MRI) evaluates orbital pathology not visualized by an ophthalmologic examination. This study combined orbital and cranial vessel wall MRI to assess both orbital and cranial disease activity in patients with GCA, including patients without visual symptoms.MethodsPatients with suspected active GCA who underwent orbital and cranial vessel wall MRI were included. In 14 patients, repeat imaging over 12 months assessed sensitivity to change. Clinical diagnosis of ocular or nonocular GCA was determined by a rheumatologist and/or ophthalmologist. A radiologist masked to clinical data scored MRI enhancement of structures.ResultsSixty‐four patients with suspected GCA were included: 25 (39%) received a clinical diagnosis of GCA, including 12 (19%) with ocular GCA. Orbital MRI enhancement was observed in 83% of patients with ocular GCA, 38% of patients with nonocular GCA, and 5% of patients with non‐GCA. MRI had strong diagnostic performance for both any GCA and ocular GCA. Combining MRI with a funduscopic examination reached 100% sensitivity for ocular GCA. MRI enhancement significantly decreased after treatment (P < 0.01).ConclusionIn GCA, MRI is a sensitive tool that comprehensively evaluates multiple cranial structures, including the orbits, which are the most concerning site of pathology. Orbital enhancement in patients without visual symptoms suggests that MRI may detect at‐risk subclinical ocular disease in GCA. MRI scores decreased following treatment, suggesting scores reflect inflammation. Future studies are needed to determine if MRI can identify patients at low risk for blindness who may receive less glucocorticoid therapy.
GMOCU: Digital Documentation, Management, and Biological Risk Assessment of Genetic Parts
Authors: Wagner Christoph , Urquiza‐Garcia Uriel , Zurbriggen Matias D. , Beyer Hannes M. 
Published: January 2024

AbstractThe continuous evolution of molecular biology and gene synthesis methods paired with an ever‐increasing potential of synthetic biology approaches and genome engineering toolkits enables the rapid design of genetic bioparts and genetically modified organisms. Although various software solutions assist with specific design tasks and challenges, lab internal documentation and ensuring compliance with governmental regulations on biosafety assessment of the generated organisms remain the responsibility of individual academic researchers. This results in inconsistent and redundant documentation regimes and a significant time and labor burden. GMOCU (GMO documentation) is a standardized semi‐automatic user‐oriented software approach —written in Python and freely available— that unifies lab internal data documentation on genetic parts and genetically modified organisms (GMOs). It automatizes biological risk evaluations and maintains a shared up‐to‐date inventory of bioparts for team‐wide data navigation and sharing. GMOCU further enables data export into customizable formats suitable for scientific publications, official biosafety documents, and the research community.