bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial uncouplers inhibit hepatic stellate cell activation
Authors: Guimarães Eduardo L , Best Jan , Dollé Laurent , Najimi Mustapha , Sokal Etienne , van Grunsven Leo A 
Published: September 2012

Abstract

Background
Mitochondrial dysfunction participates in the progression of several pathologies. Although there is increasing evidence for a mitochondrial role in liver disease, little is known about its contribution to hepatic stellate cell (HSC) activation. In this study we investigated the role of mitochondrial activity through mild uncoupling during in vitro activation of HSCs.

Methods
Cultured primary human and mouse HSCs were treated with the chemical uncouplers FCCP and Valinomycin. ATP levels were measured by luciferase assay and production of reactive oxygen species was determined using the fluorescent probe DCFH-DA. Possible cytotoxicity by uncoupler treatment was evaluated by caspase 3/7 activity and cytoplasmic protease leakage. Activation of HSCs and their response to the pro-fibrogenic cytokine TGF-β was evaluated by gene expression of activation markers and signal mediators using RT-qPCR. Proliferation was measured by incorporation of EdU and protein expression of α-smooth muscle actin was analyzed by immunocytochemistry and western blot.

Results
FCCP and Valinomycin treatment mildly decreased ATP and reactive oxygen species levels. Both uncouplers increased the expression of mitochondrial genes such as Tfam and COXIV while inducing morphological features of quiescent mouse HSCs and abrogating TGF-β signal transduction. Mild uncoupling reduced HSC proliferation and expression of pro-fibrogenic markers of mouse and human HSCs.

Conclusions
Mild mitochondrial uncoupling inhibits culture-induced HSC activation and their response to pro-fibrogenic cytokines like TGF-β. These results therefore suggest mitochondrial uncoupling of HSCs as a strategy to reduce progression of liver fibrosis.
Effect of LED emission cross-section in indoor visible light communication systems
Authors: Nguyen Huy Quang , Choi Joon-Ho , Kang Tae-Gyu , Lim Sang-Kyu , Kim Dae Ho , Kang Moonsoo , Lee Chung Ghiu 
Published: September 2012

Abstract
Visible light communication (VLC) is an optical wireless communication technology that uses visible light emitting diodes (LEDs) as a communication source. Since the LEDs are also used for illumination, the cross-section emission effects of the LEDs need to be analyzed as they apply to indoor VLC channels. In order to evaluate the illumination and communication performance according to the emission cross-section pattern a simple LED model with a quasi-elliptic emission cross-section is proposed and compared to a circular LED model.
The spatial distributions of the received optical power and root mean square delay spread are analyzed through calculation and comparison. The LEDs with a quasi-elliptic emission cross-section provide less fluctuation in the illumination and optical power distribution at the receiving plane. However, the RMS delay spread increases and subsequently the maximum data rate decreases for the quasi-elliptic emission cross-section LEDs. The single transmitter VLC system is found to support at least 17 and 24 Mb/s for circular and quasi-elliptic emission cross-section LEDs for the entire receiving plane, respectively. The four-transmitter VLC system is found to support at least at 30 and 33 Mb/s for circular and quasi-elliptic emission cross-section LEDs for the entire receiving plane, respectively.
Oncogenic human papillomavirus genital infection in southern Iranian women: population-based study versus clinic-based data
Authors: Eghbali Seyed Sajjad , Amirinejad Roya , Obeidi Narges , Mosadeghzadeh Shiva , Vahdat Katayoun , Azizi Fatemeh , Pazoki Raha , Sanjdideh Zahra , Amiri Zahra , Nabipour Iraj , Zandi Keivan 
Published: September 2012

AbstractBackgroundEpidemiological studies on genital human papilloma viruses infection (HPVs) in general population are crucial for the implementation of health policy guidelines for developing the strategies to prevent the primary and secondary cervical cancer. In different parts of Iran, there is a lack of population-based studies to determine the prevalence of HPV in the general population. The aim of this population-based study is to compare the prevalence rate of genital HPV infection among reproductive women with our previous clinic-based data, which showed a prevalence rate of 5% in women in southern Iran.ResultsUsing general primers for all genotypes of HPV, of 799 randomly selected women, five (0.63%, 95% CI 0.23-1.55%) tested positive for HPV DNA. Overall, seven different HPV genotypes were detected: six types (16, 18, 31, 33, 51 and 56) were carcinogenic, or “high risk genotypes” and one genotype (HPV-66) was “probably carcinogenic.”ConclusionsIn a population-based study, the prevalence of HPV infection among southern Iranian women was lower than that observed worldwide. However, our gynaecological clinic-based study on the prevalence of HPV infection showed results comparable with other studies in the Middle East and Persian Gulf countries. Since gynaecological clinic-based data may generally overestimate HPV prevalence, estimates of prevalence according to clinic-based data should be adjusted downward by the population-based survey estimates.
Production and characterization of human anti-V3 monoclonal antibodies from the cells of HIV-1 infected Indian donors
Authors: Andrabi Raiees , Kumar Rajesh , Bala Manju , Nair Ambili , Biswas Ashutosh , Wig Naveet , Kumar Pratik , Pal Rahul , Sinha Subrata , Luthra Kalpana 
Published: September 2012

AbstractBackgroundAnalysis of human monoclonal antibodies (mAbs) developed from HIV-1 infected donors have enormously contributed to the identification of neutralization sensitive epitopes on the HIV-1 envelope glycoprotein. The third variable region (V3) is a crucial target on gp120, primarily due to its involvement in co-receptor (CXCR4 or CCR5) binding and presence of epitopes recognized by broadly neutralizing antibodies.MethodsThirty-three HIV-1 seropositive drug naive patients (18 males and 15 females) within the age range of 20–57 years (median = 33 years) were recruited in this study for mAb production. The mAbs were selected from EBV transformed cultures with conformationally constrained Cholera-toxin-B containing V3C (V3C-CTB) fusion protein. We tested the mAbs for their binding with HIV-1 derived proteins and peptides by ELISA and for neutralization against HIV-1 viruses by TZM-bl assays.ResultsWe isolated three anti-V3 mAbs, 277, 903 and 904 from the cells of different individuals. The ELISA binding revealed a subtype-C and subtype-A specific binding of antibody 277 and 903 while mAb 904 exhibited cross reactivity also with subtype-B V3. Epitope mapping of mAbs with overlapping V3 peptides showed exclusive binding to V3 crown. The antibodies displayed high and low neutralizing activity against 2/5 tier 1 and 1/6 tier 2 viruses respectively. Overall, we observed a resistance of the tier 2 viruses to neutralization by the anti-V3 mAbs, despite the exposure of the epitopes recognized by these antibodies on two representative native viruses (Du156.12 and JRFL), suggesting that the affinity of mAb might equally be crucial for neutralization, as the epitope recognition.ConclusionsOur study suggests that the anti-V3 antibodies derived from subtype-C infected Indian patients display neutralization potential against tier 1 viruses while such activity may be limited against more resistant tier 2 viruses. Defining the fine epitope specificities of these mAbs and further experimental manipulations will be helpful in identification of epitopes, unique to clade C or shared with non-clade C viruses, in context of V3 region.
Early postnatal low-protein nutrition, metabolic programming and the autonomic nervous system in adult life
Authors: de Oliveira Júlio Cezar , Grassiolli Sabrina , Gravena Clarice , de Mathias Paulo Cezar Freitas 
Published: September 2012

Abstract
Protein restriction during lactation has been used as a rat model of metabolic programming to study the impact of perinatal malnutrition on adult metabolism. In contrast to protein restriction during fetal life, protein restriction during lactation did not appear to cause either obesity or the hallmarks of metabolic syndrome, such as hyperinsulinemia, when individuals reached adulthood. However, protein restriction provokes body underweight and hypoinsulinemia. This review is focused on the regulation of insulin secretion and the influence of the autonomic nervous system (ANS) in adult rats that were protein-malnourished during lactation. The data available on the topic suggest that the perinatal phase of lactation, when insulted by protein deficit, imprints the adult metabolism and thereby alters the glycemic control. Although hypoinsulinemia programs adult rats to maintain normoglycemia, pancreatic β-cells are less sensitive to secretion stimuli, such as glucose and cholinergic agents. These pancreatic dysfunctions may be attributed to an imbalance of ANS activity recorded in adult rats that experienced maternal protein restriction.
NAAG Peptidase Inhibition in the Periaqueductal Gray and Rostral Ventromedial Medulla Reduces Flinching in the Formalin Model of Inflammation
Authors: Yamada Toshihiko , Zuo Daiying , Yamamoto Tatsuo , Olszewski Rafal T , Bzdega Tomasz , Moffett John R , Neale Joseph H 
Published: September 2012

Background: Metabotropic glutamate receptors (mGluRs) have been identified as significant analgesic targets. Systemic treatments with inhibitors of the enzymes that inactivate the peptide transmitter N-acetylaspartylglutamate (NAAG), an mGluR3 agonist, have an analgesia-like effect in rat models of inflammatory and neuropathic pain. The goal of this study was to begin defining locations within the central pain pathway at which NAAG activation of its receptor mediates this effect. Results: NAAG immunoreactivity was found in neurons in two brain regions that mediate nociceptive processing, the periaqueductal gray (PAG) and the rostral ventromedial medulla (RVM). Microinjection of the NAAG peptidase inhibitor ZJ43 into the PAG contralateral, but not ipsilateral, to the formalin injected footpad reduced the rapid and slow phases of the nociceptive response in a dose-dependent manner. ZJ43 injected into the RVM also reduced the rapid and slow phase of the response. The group II mGluR antagonist LY341495 blocked these effects of ZJ43 on the PAG and RVM. NAAG peptidase inhibition in the PAG and RVM did not affect the thermal withdrawal response in the hot plate test. Footpad inflammation also induced a significant increase in glutamate release in the PAG. Systemic injection of ZJ43 increased NAAG levels in the PAG and RVM and blocked the inflammation-induced increase in glutamate release in the PAG. Conclusion: These data demonstrate a behavioral and neurochemical role for NAAG in the PAG and RVM in regulating the spinal motor response to inflammation and that NAAG peptidase inhibition has potential as an approach to treating inflammatory pain via either the ascending (PAG) and/or the descending pain pathways (PAG and RVM) that warrants further study.
Thromboembolic stroke in C57BL/6 mice monitored by 9.4 T MRI using a 1H cryo probe
Authors: Langhauser Friederike L , Heiler Patrick M , Grudzenski Saskia , Lemke Andreas , Alonso Angelika , Schad Lothar R , Hennerici Michael G , Meairs Stephen , Fatar Marc 
Published: September 2012

Abstract

Background
A new thromboembolic animal model showed beneficial effects of t-PA with an infarct volume reduction of 36.8% in swiss mice. Because knock-out animal experiments for stroke frequently used C57BL76 mice we evaluated t-PA effects in this mouse strain and measured infarct volume and vascular recanalisation in-vivo by using high-field 9.4 T MRI and a 1H surface cryo coil.

Methods
Clot formation was triggered by microinjection of murine thrombin into the right middle cerebral artery (MCA). Animals (n = 28) were treated with 10 mg/kg, 5 mg/kg or no tissue plasminogen activator (t-PA) 40 min after MCA occlusion. For MR-imaging a Bruker 9.4 T animal system with a 1H surface cryo probe was used and a T2-weighted RARE sequence, a diffusion weighted multishot EPI sequence and a 3D flow-compensated gradient echo TOF angiography were performed.

Results
The infarct volume in animals treated with t-PA was significantly reduced (0.67 ± 1.38 mm3 for 10 mg/kg and 10.9 ± 8.79 mm3 for 5 mg/kg vs. 19.76 ± 2.72 mm3 ; p < 0.001) compared to untreated mice. An additional group was reperfused with t-PA inside the MRI. Already ten minutes after beginning of t-PA treatment, reperfusion flow was re-established in the right MCA. However, signal intensity was lower than in the contralateral MCA. This reduction in cerebral blood flow was attenuated during the first 60 minutes after reperfusion. 24 h after MCA occlusion and reperfusion, no difference in signal intensity of the contralateral and ipsilateral MCAs was observed.

Conclusions
We confirm a t-Pa effect using this stroke model in the C57BL76 mouse strain and demonstrate a chronological sequence MRI imaging after t-PA using a 1H surface cryo coil in a 9.4 T MRI. This setting will allow testing of new thrombolytic strategies for stroke treatment in-vivo in C57BL76 knock-out mice.
Effects of HIV-1 protease on cellular functions and their potential applications in antiretroviral therapy
Authors: Yang Hailiu , Nkeze Joseph , Zhao Richard Y 
Published: September 2012

AbstractHuman Immunodeficiency Virus Type 1 (HIV-1) protease inhibitors (PIs) are the most potent class of drugs in antiretroviral therapies. However, viral drug resistance to PIs could emerge rapidly thus reducing the effectiveness of those drugs. Of note, all current FDA-approved PIs are competitive inhibitors,i.e., inhibitors that compete with substrates for the active enzymatic site. This common inhibitory approach increases the likelihood of developing drug resistant HIV-1 strains that are resistant to many or all current PIs. Hence, new PIs that move away from the current target of the active enzymatic site are needed. Specifically, allosteric inhibitors, inhibitors that prohibit PR enzymatic activities through non-competitive binding to PR, should be sought. Another common feature of current PIs is they were all developed based on the structure-based design. Drugs derived from a structure-based strategy may generate target specific and potent inhibitors. However, this type of drug design can only target one site at a time and drugs discovered by this method are often associated with strong side effects such as cellular toxicity, limiting its number of target choices, efficacy, and applicability. In contrast, a cell-based system may provide a useful alternative strategy that can overcome many of the inherited shortcomings associated with structure-based drug designs. For example, allosteric PIs can be sought using a cell-based system without considering the site or mechanism of inhibition. In addition, a cell-based system can eliminate those PIs that have strong cytotoxic effect. Most importantly, a simple, economical, and easy-to-maintained eukaryotic cellular system such as yeast will allow us to search for potential PIs in a large-scaled high throughput screening (HTS) system, thus increasing the chances of success. Based on our many years of experience in using fission yeast as a model system to study HIV-1 Vpr, we propose the use of fission yeast as a possible surrogate system to study the effects of HIV-1 protease on cellular functions and to explore its utility as a HTS system to search for new PIs to battle HIV-1 resistant strains.
Ultrasound of metacarpophalangeal joints is a sensitive and reliable endpoint for drug therapies in rheumatoid arthritis: results of a randomized, two-center placebo-controlled study
Authors: Seymour Matthew W , Kelly Stephen , Beals Chan R , Malice Marie-Pierre , Bolognese James A , Dardzinski Bernard J , Cheng Amy S , Cummings Corinne E , Smugar Steven S , McClinton Catherine , Fox Amy , Dooley William M , Pitzalis Constantino , Taylor Peter C 
Published: September 2012

Abstract
Introduction
We aimed to investigate the sensitivity and reliability of two-dimensional ultrasonographic endpoints at the metacarpophalageal joints (MCPJs) and their potential to provide an early and objective indication of a therapeutic response to treatment intervention in rheumatoid arthritis (RA).

Methods
A randomized, double-blind, parallel-group, two-center, placebo-controlled trial investigated the effect on ultrasonographic measures of synovitis of repeat dose oral prednisone, 15mg or 7.5mg, each compared to placebo, in consecutive two-week studies; there were 18 subjects in a 1:1 ratio and 27 subjects in a 2:1 ratio, respectively. All subjects met the 1987 American College of Rheumatology criteria for the diagnosis of RA, were ≥18 years-old with RA disease duration ≥6 months, and had a Disease Activity Score 28 based on C-reactive protein (DAS28(CRP)) ≥3.2. Subjects underwent high-frequency (gray-scale) and power Doppler ultrasonography at Days 1 (baseline), 2, 8 and 15 in the dorsal transverse and longitudinal planes of all 10 MCPJs to obtain summated scores of quantitative and semi-quantitative measures of synovial thickness as well as vascularity. The primary endpoint was the summated score of power Doppler area measured quantitatively in all 10 MCPJs in the transverse plane at Day 15. Clinical efficacy was assessed at the same time points by DAS28(CRP).

Results
All randomized subjects completed the trial. The comparison between daily 15 mg prednisone and placebo at Day 15 yielded a statistically significant treatment effect (effect size = 1.17, P = 0.013) in change from baseline in the primary endpoint, but borderline for prednisone 7.5 mg daily versus placebo (effect size = 0.61, P = 0.071). A significant treatment effect for DAS28(CRP) was only observed at Day 15 in the prednisone 15 mg group (effect size = 0.95, P = 0.032). However, significant treatment effects at all time points for a variety of ultrasound (US) endpoints were detected with both prednisone doses; the largest observed effect size = 2.33. Combining US endpoints with DAS28(CRP) improved the registration of significant treatment effects. The parallel scan inter-reader reliability of summated 10 MCPJ scores were good to excellent (ICC values >0.61) for the majority of US measures.

Conclusions
Ultrasonography of MCPJs is an early, reliable indicator of therapeutic response in RA with potential to reduce patient numbers and length of trials designed to give preliminary indications of efficacy.

Trial Registration
Clinicaltrials.gov identifier: NCT00746512
Quantitative assessment of invasive mena isoforms (Menacalc) as an independent prognostic marker in breast cancer
Authors: Agarwal Seema , Gertler Frank B , Balsamo Michele , Condeelis John S , Camp Robert L , Xue Xiaonan , Lin Juan , Rohan Thomas E , Rimm David L 
Published: September 2012

Abstract
Introduction
Mena, an Ena/VASP protein family member, is a key actin regulatory protein. Mena is up-regulated in breast cancers and promotes invasion and motility of tumor cells. Mena has multiple splice variants, including Mena invasive (MenaINV) and Mena11a, which are expressed in invasive or non-invasive tumor cells, respectively. We developed a multiplex quantitative immunofluorescence (MQIF) approach to assess the fraction of Mena lacking 11a sequence as a method to infer the presence of invasive tumor cells represented as total Mena minus Mena11a (called Menacalc) and determined its association with metastasis in breast cancer.

Methods
The MQIF method was applied to two independent primary breast cancer cohorts (Cohort 1 with 501 and Cohort 2 with 296 patients) using antibodies against Mena and its isoform, Mena11a. Menacalc was determined for each patient and assessed for association with risk of disease-specific death.

Results
Total Mena or Mena11a isoform expression failed to show any statistically significant association with outcome in either cohort. However, assessment of Menacalc showed that relatively high levels of this biomarker is associated with poor outcome in two independent breast cancer cohorts (log rank P = 0.0004 for Cohort 1 and 0.0321 for Cohort 2). Multivariate analysis on combined cohorts revealed that high Menacalc is associated with poor outcome, independent of age, node status, receptor status and tumor size.

Conclusions
High Menacalc levels identify a subgroup of breast cancer patients with poor disease-specific survival, suggesting that Menacalc may serve as a biomarker for metastasis.
Choice of hospital after out-of-hospital cardiac arrest - a decision with far-reaching consequences: a study in a large German city
Authors: Wnent Jan , Seewald Stephan , Heringlake Matthias , Lemke Hans , Brauer Kirk , Lefering Rolf , Fischer Matthias , Jantzen Tanja , Bein Berthold , Messelken Martin , Gräsner Jan-Thorsten 
Published: September 2012

Abstract
Introduction
Between 1 and 31% of patients suffering out-of-hospital cardiac arrest (OHCA) survive to discharge from hospital. International studies have shown that the level of care provided by the admitting hospital determines survival for patients suffering from OHCA. These data may only be partially transferable to the German medical system where responders are in-field emergency medical physicians. The present study determines the influence of the emergency physician's choice of admitting hospital on patient outcome after OHCA in a large urban setting.

Methods
All data for patients collected in the German Resuscitation Registry for the city of Dortmund during 2007 and 2008 were analyzed. Patients under 18 years of age, with traumatic mechanism, and with incomplete charts were excluded. Admitting hospitals were divided into two groups: those without the capability for percutaneous coronary intervention (PCI), and those with PCI capability. Data were analyzed by multivariate statistics, taking into account the effects of mild therapeutic hypothermia treatment and PCI capability of the admitting hospital with respect to the neurological status upon hospital discharge.

Results
Between 2007 and 2008 a total of 1,109 cardiopulmonary resuscitation attempts were registered for the city of Dortmund, of which 889 could be included in our study. Return of spontaneous circulation was achieved in 360 of 889 patients (40.5%). In total, 282 of 889 patients displayed return of spontaneous circulation during transport to the hospital (31.7%); 152 were transported with ongoing cardiopulmonary resuscitation (17.1%). Of the total 434 patients admitted to hospital, 264 were admitted to hospitals without PCI capability and 170 to hospitals with PCI capability. Multivariate analysis demonstrated a significant influence on patient discharge with good neurological status for those admitted to PCI hospitals (odds ratio 3.14 (95% confidence interval 1.51 to 6.56)), independent of receiving mild therapeutic hypothermia and/or PCI. Compared with patients admitted to hospitals without PCI capability, significantly more patients in PCI hospitals were discharged alive (41% vs. 13%, P < 0.001) and remained alive 1 year after the event (28% vs. 6%, P < 0.001).

Conclusions
The choice of admitting hospital for patients suffering OHCA significantly influences treatment and outcome. This influence is independent of PCI performance and of mild therapeutic hypothermia. Further analysis is required to determine the possible parameters determining patient outcome.