bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of simian T-cell leukemia virus type 1 in naturally infected Japanese macaques as a model of HTLV-1 infection
Authors: Miura Michi , Yasunaga Jun-ichiro , Tanabe Junko , Sugata Kenji , Zhao Tiejun , Ma Guangyong , Miyazato Paola , Ohshima Koichi , Kaneko Akihisa , Watanabe Akino , Saito Akatsuki , Akari Hirofumi , Matsuoka Masao 
Published: October 2013

Abstract

Background
Human T-cell leukemia virus type 1 (HTLV-1) causes chronic infection leading to development of adult T-cell leukemia (ATL) and inflammatory diseases. Non-human primates infected with simian T-cell leukemia virus type 1 (STLV-1) are considered to constitute a suitable animal model for HTLV-1 research. However, the function of the regulatory and accessory genes of STLV-1 has not been analyzed in detail. In this study, STLV-1 in naturally infected Japanese macaques was analyzed.

Results
We identified spliced transcripts of STLV-1 corresponding to HTLV-1 tax and HTLV-1 bZIP factor (HBZ). STLV-1 Tax activated the NFAT, AP-1 and NF-κB signaling pathways, whereas STLV-1 bZIP factor (SBZ) suppressed them. Conversely, SBZ enhanced TGF-β signaling and induced Foxp3 expression. Furthermore, STLV-1 Tax activated the canonical Wnt pathway while SBZ suppressed it. STLV-1 Tax enhanced the viral promoter activity while SBZ suppressed its activation. Then we addressed the clonal proliferation of STLV-1+ cells by massively sequencing the provirus integration sites. Some clones proliferated distinctively in monkeys with higher STLV-1 proviral loads. Notably, one of the monkeys surveyed in this study developed T-cell lymphoma in the brain; STLV-1 provirus was integrated in the lymphoma cell genome. When anti-CCR4 antibody, mogamulizumab, was administered into STLV-1-infected monkeys, the proviral load decreased dramatically within 2 weeks. We observed that some abundant clones recovered after discontinuation of mogamulizumab administration.

Conclusions
STLV-1 Tax and SBZ have functions similar to those of their counterparts in HTLV-1. This study demonstrates that Japanese macaques naturally infected with STLV-1 resemble HTLV-1 carriers and are a suitable model for the investigation of persistent HTLV-1 infection and asymptomatic HTLV-1 carrier state. Using these animals, we verified that mogamulizumab, which is currently used as a drug for relapsed ATL, is also effective in reducing the proviral load in asymptomatic individuals.
Reactivation of latent HIV-1 in central memory CD4+T cells through TLR-1/2 stimulation
Authors: Novis Camille L , Archin Nancie M , Buzon Maria J , Verdin Eric , Round June L , Lichterfeld Mathias , Margolis David M , Planelles Vicente , Bosque Alberto 
Published: October 2013

AbstractBackgroundToll-like receptors (TLRs) are crucial for recognition of pathogen-associated molecular patterns by cells of the innate immune system. TLRs are present and functional in CD4+T cells. Memory CD4+T cells, predominantly central memory cells (TCM), constitute the main reservoir of latent HIV-1. However, how TLR ligands affect the quiescence of latent HIV within central memory CD4+T cells has not been studied.ResultsWe evaluated the ability of a broad panel of TLR agonists to reactivate latent HIV-1. The TLR-1/2 agonist Pam3CSK4 leads to viral reactivation of quiescent HIV in a model of latency based on cultured TCMand in resting CD4+T cells isolated from aviremic patients. In addition, we investigated the signaling pathway associated with Pam3CSK4 involved in HIV-1 reactivation. We show that the transcription factors NFκB, NFAT and AP-1 cooperate to induce viral reactivation downstream of TLR-1/2 stimulation. Furthermore, increasing levels of cyclin T1 is not required for TLR-mediated viral reactivation, but induction of viral expression requires activated pTEFb. Finally, Pam3CSK4 reactivates latent HIV-1 in the absence of T cell activation or proliferation, in contrast to antigen stimulation.ConclusionsOur findings suggest that the signaling through TLR-1/2 pathway via Pam3CSK4 or other reagents should be explored as an anti-latency strategy either alone or in combination with other anti-latency drugs.
Proteasome inhibitors act as bifunctional antagonists of human immunodeficiency virus type 1 latency and replication
Authors: Miller Leia K , Kobayashi Yoshifumi , Chen Chiann-Chyi , Russnak Timothy A , Ron Yacov , Dougherty Joseph P 
Published: October 2013

AbstractBackgroundExisting highly active antiretroviral therapy (HAART) effectively controls viral replication in human immunodeficiency virus type 1 (HIV-1) infected individuals but cannot completely eradicate the infection, at least in part due to the persistence of latently infected cells. One strategy that is being actively pursued to eliminate the latent aspect of HIV-1 infection involves therapies combining latency antagonists with HAART. However, discordant pharmacokinetics between these types of drugs can potentially create sites of active viral replication within certain tissues that might be impervious to HAART.ResultsA preliminary reverse genetic screen indicated that the proteasome might be involved in the maintenance of the latent state. This prompted testing to determine the effects of proteasome inhibitors (PIs) on latently infected cells. Experiments demonstrated that PIs effectively activated latent HIV-1 in several model systems, including primary T cell models, thereby defining PIs as a new class of HIV-1 latency antagonists. Expanding upon experiments from previous reports, it was also confirmed that PIs inhibit viral replication. Moreover, it was possible to show that PIs act as bifunctional antagonists of HIV-1. The data indicate that PIs activate latent provirus and subsequently decrease viral titers and promote the production of defective virions from activated cells.ConclusionsThese results represent a proof-of-concept that bifunctional antagonists of HIV-1 can be developed and have the capacity to ensure precise tissue overlap of anti-latency and anti-replication functions, which is of significant importance in the consideration of future drug therapies aimed at viral clearance.
Sub-threshold spinal cord stimulation facilitates spontaneous motor activity in spinal rats
Authors: Gad Parag , Choe Jaehoon , Shah Prithvi , Garcia-Alias Guillermo , Rath Mrinal , Gerasimenko Yury , Zhong Hui , Roy Roland R , Edgerton Victor Reggie 
Published: October 2013

Abstract

Background
Epidural stimulation of the spinal cord can be used to enable stepping on a treadmill (electrical enabling motor control, eEmc) after a complete mid-thoracic spinal cord transection in adult rats. Herein we have studied the effects of eEmc using a sub-threshold intensity of stimulation combined with spontaneous load-bearing proprioception to facilitate hindlimb stepping and standing during daily cage activity in paralyzed rats.

Methods
We hypothesized that eEmc combined with spontaneous cage activity would greatly increase the frequency and level of activation of the locomotor circuits in paralyzed rats. Spontaneous cage activity was recorded using a specially designed swivel connector to record EMG signals and an IR based camcorder to record video.

Results and conclusion
The spinal rats initially were very lethargic in their cages showing little movement. Without eEmc, the rats remained rather inactive with the torso rarely being elevated from the cage floor. When the rats used their forelimbs to move, the hindlimbs were extended and dragged behind with little or no flexion. In contrast, with eEmc the rats were highly active and the hindlimbs showed robust alternating flexion and extension resulting in step-like movements during forelimb-facilitated locomotion and often would stand using the sides of the cages as support. The mean and summed integrated EMG levels in both a hindlimb flexor and extensor muscle were higher with than without eEmc. These data suggest that eEmc, in combination with the associated proprioceptive input, can modulate the spinal networks to significantly amplify the amount and robustness of spontaneous motor activity in paralyzed rats.
Recovery of archaeological wall paintings using novel multispectral imaging approaches
Authors: Legnaioli Stefano , Lorenzetti Giulia , Cavalcanti Gildo H , Grifoni Emanuela , Marras Luciano , Tonazzini Anna , Salerno Emanuele , Pallecchi Pasquino , Giachi Gianna , Palleschi Vincenzo 
Published: October 2013

Abstract
New approaches in the application of multispectral imaging to the recovery of archeological wall paintings are presented, based on statistical techniques and on a novel method of image treatment (Chromatic Derivative Imaging – ChromaDI) which offers a way of embedding information coming from four spectral bands into a standard RGB image. The methods are applied to some wall paintings from the Tomb of the Monkey, an Etruscan tomb in the necropolis of Poggio Renzo, near the city of Chiusi (Siena), Italy, dated around 480-470 BC. It is shown that the techniques described are able to highlight and enhance a number of details that cannot be perceived in either any of the original channel images or any single processed output channel.
Prior criminal charges and outcomes among individuals initiating office-based buprenorphine treatment
Authors: Harris Elizabeth E , Jacapraro Janet S , Rastegar Darius A 
Published: October 2013

Abstract

Background
There is little data on the impact of prior criminal activity on the treatment of opioid dependence with office-based buprenorphine. The goal of this study was to investigate the association between prior criminal charges and treatment outcomes in a cohort of patients initiating buprenorphine treatment in a primary care practice.

Methods
This was a retrospective study of 252 consecutive patients with opioid dependence who were given at least one prescription for buprenorphine in a primary care practice. A public database was used to collect data on criminal charges prior to enrollment. For every month after initiation of treatment, patients who remained in treatment were classified as “opioid-positive” or “opioid-negative” based on urine drug test results, patient report and clinician assessment. The primary outcomes of interest were treatment retention at one year and achieving ≥ 6 “opioid negative” months.

Results
Most (80%) of the subjects had at least one prior criminal charge. Those with prior criminal charges were more likely to have Medicare or Medicaid insurance, to be unemployed, to use cocaine and to have injected drugs. In the year after initiation of buprenorphine treatment, these subjects had significantly less opioid-negative months than those without criminal charges (5.1 months vs. 6.4 months; p = 0.030), and were less likely to have ≥ 6 opioid-negative months (43.2% vs. 58.4%; p = 0.048). While there was no difference in treatment retention at one-year for those who had any prior history (55.4% vs. 52.0%; p = 0.854), having recent charges (in the previous two years) was associated with poorer treatment retention and drug outcomes. On the other hand, having only distant charges (more than two years prior to treatment initiation) was not associated with poorer outcomes. Using multivariate analysis, recent criminal charges was the only factor significantly associated with treatment retention at one year and achieving ≥ 6 opioid-negative months.

Conclusions
Subjects with recent criminal charges had poorer treatment retention and opioid-abstinence outcomes after initiating office-based buprenorphine treatment. These individuals may benefit from more intensive treatment than is typically offered in a primary care setting.
Neuroprotective effects of donepezil against cholinergic depletion
Authors: Cutuli Debora , De Bartolo Paola , Caporali Paola , Tartaglione Anna Maria , Oddi Diego , D’Amato Francesca Romana , Nobili Annalisa , D’Amelio Marcello , Petrosini Laura 
Published: October 2013

Abstract
Introduction
Intraparenchymal injections of the immunotoxin 192-IgG-saporin into medial septum and nucleus basalis magnocellularis causes a selective depletion of basal forebrain cholinergic neurons. Thus, it represents a valid model to mimic a key component of the cognitive deficits associated with aging and dementia. Here we administered donepezil, a potent acetylcholinesterase inhibitor developed for treating Alzheimer’s disease, 15 days before 192-IgG-saporin injection, and thus we examined donepezil effects on neurodegeneration and cognitive deficits.

Methods
Caspase-3 activity and cognitive performances of lesioned rats pre-treated with donepezil or saline were analyzed and compared to the outcomes obtained in pre-treated sham-lesioned rats.

Results
Cholinergic depletion increased hippocampal and neocortical caspase-3 activity and impaired working memory, spatial discrimination, social novelty preference, and ultrasonic vocalizations, without affecting anxiety levels and fear conditioning. In lesioned animals, donepezil pre-treatment reduced hippocampal and neocortical caspase-3 activity and improved working memory and spatial discrimination performances and partially rescued ultrasonic vocalizations, without preventing social novelty alterations.

Conclusions
Present data indicate that donepezil pre-treatment exerts beneficial effects on behavioral deficits induced by cholinergic depletion, attenuating the concomitant hippocampal and neocortical neurodegeneration.
Very different performance of the power Doppler modalities of several ultrasound machines ascertained by a microvessel flow phantom
Authors: Ten Cate David F , Luime Jolanda J , van der Ven Myrthe , Hazes Johanna MW , Kooiman Klazina , de Jong Nico , Bosch Johannes G 
Published: October 2013

Abstract
Introduction
In many patients with rheumatoid arthritis (RA) subclinical disease activity can be detected with ultrasound (US), especially using power Doppler US (PDUS). However, PDUS may be highly dependent on the type of machine. This could create problems both in clinical trials and in daily clinical practice. To clarify how the PDUS signal differs between machines we created a microvessel flow phantom.

Methods
The flow phantom contained three microvessels (150, 1000, 2000 microns). A syringe pump was used to generate flows. Five US machines were used. Settings were optimised to assess the lowest detectable flow for each US machine.

Results
The minimal detectable flow velocities showed very large differences between the machines. Only two of the machines may be able to detect the very low flows in the capillaries of inflamed joints. There was no clear relation with price. One of the lower-end machines actually performed best in all three vessel sizes.

Conclusions
We created a flow phantom to test the sensitivity of US machines to very low flows in small vessels. The sensitivity of the power Doppler modalities of 5 different machines was very different. The differences found between the machines are probably caused by fundamental differences in processing of the PD signal or internal settings inaccessible to users. Machines considered for PDUS assessment of RA patients should be tested using a flow phantom similar to ours. Within studies, only a single machine type should be used.
Pre-diagnosis oophorectomy, estrogen therapy and mortality in a cohort of women diagnosed with breast cancer
Authors: Nichols Hazel B , Trentham-Dietz Amy , Newcomb Polly A , Egan Kathleen M , Titus Linda J , Hampton John M , Visvanathan Kala 
Published: October 2013

Abstract
Introduction
Pre-diagnosis oophorectomy and estrogen therapy could impact mortality due to breast cancer and cardiovascular disease (CVD) among breast cancer survivors. Elective bilateral oophorectomy at the time of hysterectomy for benign conditions is not uncommon among US women.

Methods
We examined the association between pre-diagnosis total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAHBSO) and both overall and cause-specific mortality in the Collaborative Breast Cancer Studies cohort. Medical history and prior estrogen use were collected during standardized telephone interviews. Vital status, including date and cause of death, was obtained by linkage with the National Death Index. Multivariate hazard ratios (HR) and 95% confidence intervals (CI) for cause-specific mortality were calculated using Cox proportional hazards regression.

Results
Seventeen percent (N = 1,778) of breast cancer survivors (mean age at diagnosis = 63.5) reported pre-diagnosis TAHBSO. During follow-up (mean = 9.5 years), 2,856 deaths occurred, including 1,060 breast cancer deaths and 459 CVD deaths. Breast cancer deaths occurred a median of 5.1 years after diagnosis; CVD deaths occurred further from diagnosis (median = 9.7 years). Women who reported pre-diagnosis TAHBSO had a 16% decrease in all-cause mortality (HR = 0.84; 95% CI: 0.76, 0.92) compared to those with an intact uterus and ovaries. This overall decrease reflected a 27% lower breast cancer mortality among women who never used postmenopausal hormones (HR = 0.73; CI: 0.55, 0.96) and 43% lower CVD risk among women who reported using estrogen (HR = 0.57; CI: 0.39, 0.83) after TAHBSO.

Conclusions
Information on prior TAHBSO and estrogen use can inform risk of death from both breast cancer and cardiovascular disease among breast cancer survivors.
AVISPA: a web tool for the prediction and analysis of alternative splicing
Authors: Barash Yoseph , Vaquero-Garcia Jorge , González-Vallinas Juan , Xiong Hui Yuan , Gao Weijun , Lee Leo J , Frey Brendan J 
Published: October 2013

AbstractTranscriptome complexity and its relation to numerous diseases underpins the need to predict in silico splice variants and the regulatory elements that affect them. Building upon our recently described splicing code, we developed AVISPA, a Galaxy-based web tool for splicing prediction and analysis. Given an exon and its proximal sequence, the tool predicts whether the exon is alternatively spliced, displays tissue-dependent splicing patterns, and whether it has associated regulatory elements. We assess AVISPA's accuracy on an independent dataset of tissue-dependent exons, and illustrate how the tool can be applied to analyze a gene of interest. AVISPA is available at http://avispa.biociphers.org.
Sequence signatures extracted from proximal promoters can be used to predict distal enhancers
Authors: Taher Leila , Smith Robin P , Kim Mee J , Ahituv Nadav , Ovcharenko Ivan 
Published: October 2013

Abstract
Background
Gene expression is controlled by proximal promoters and distal regulatory elements such as enhancers. While the activity of some promoters can be invariant across tissues, enhancers tend to be highly tissue-specific.

Results
We compiled sets of tissue-specific promoters based on gene expression profiles of 79 human tissues and cell types. Putative transcription factor binding sites within each set of sequences were used to train a support vector machine classifier capable of distinguishing tissue-specific promoters from control sequences. We obtained reliable classifiers for 92% of the tissues, with an area under the receiver operating characteristic curve between 60% (for subthalamic nucleus promoters) and 98% (for heart promoters). We next used these classifiers to identify tissue-specific enhancers, scanning distal non-coding sequences in the loci of the 200 most highly and lowly expressed genes. Thirty percent of reliable classifiers produced consistent enhancer predictions, with significantly higher densities in the loci of the most highly expressed compared to lowly expressed genes. Liver enhancer predictions were assessed in vivo using the hydrodynamic tail vein injection assay. Fifty-eight percent of the predictions yielded significant enhancer activity in the mouse liver, whereas a control set of five sequences was completely negative.

Conclusions
We conclude that promoters of tissue-specific genes often contain unambiguous tissue-specific signatures that can be learned and used for the de novo prediction of enhancers.
Temporal dynamics and transcriptional control using single-cell gene expression analysis
Authors: Kouno Tsukasa , de Hoon Michiel , Mar Jessica C , Tomaru Yasuhiro , Kawano Mitsuoki , Carninci Piero , Suzuki Harukazu , Hayashizaki Yoshihide , Shin Jay W 
Published: October 2013

Abstract
Background
Changes in environmental conditions lead to expression variation that manifest at the level of gene regulatory networks. Despite a strong understanding of the role noise plays in synthetic biological systems, it remains unclear how propagation of expression heterogeneity in an endogenous regulatory network is distributed and utilized by cells transitioning through a key developmental event.

Results
Here we investigate the temporal dynamics of a single-cell transcriptional network of 45 transcription factors in THP-1 human myeloid monocytic leukemia cells undergoing differentiation to macrophages. We systematically measure temporal regulation of expression and variation by profiling 120 single cells at eight distinct time points, and infer highly controlled regulatory modules through which signaling operates with stochastic effects. This reveals dynamic and specific rewiring as a cellular strategy for differentiation. The integration of both positive and negative co-expression networks further identifies the proto-oncogene MYB as a network hinge to modulate both the pro- and anti-differentiation pathways.

Conclusions
Compared to averaged cell populations, temporal single-cell expression profiling provides a much more powerful technique to probe for mechanistic insights underlying cellular differentiation. We believe that our approach will form the basis of novel strategies to study the regulation of transcription at a single-cell level.