bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of functional mannose receptor in a continuous hybridoma cell line
Authors: Vigerust David J , Vick Sherell , Shepherd Virginia L
Published: September 2012

Background

The mannose receptor is the best described member of the type I transmembrane C-type lectins; however much remains unanswered about the biology of the receptor. One difficulty has been the inability to consistently express high levels of a functional full length mannose receptor cDNA in mammalian cells. Another difficulty has been the lack of a human macrophage cell line expressing a fully functional receptor. Commonly used human macrophage cell lines such as U937, THP-1, Mono-Mac and HL60 do not express the mannose receptor. We have developed a macrophage hybridoma cell line (43MRcells) created by fusion of U937 cells with primary human monocyte-derived macrophages, resulting in a non-adherent cell line expressing several properties of primary macrophages. The purpose of this study was to identify and select mannose receptor-expressing cells using fluorescence-activated cell sorting and to characterize the expression and function of the receptor.

Results

In the current study we show that the mannose receptor found on this novel cell has endocytic characteristics consistent with and similar to the mannose receptor found on the surface of monocyte-derived human macrophages and rat bone marrow-derived macrophages. In addition, we demonstrate that these cells engage and internalize pathogen particles such asS. aureusandC. albicans.We further establish the transfectability of these cells via the introduction of a plasmid expressing influenza A hemagglutinin.

Conclusions

The 43MRcell line represents the first naturally expressed MR-positive cell line derived from a human macrophage background. This cell line provides an important cell model for other researchers for the study of human MR biology and host-pathogen interactions.
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

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

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

Background

Epidemiological 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.

Results

Using 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.”

Conclusions

In 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

Background

Analysis 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.

Methods

Thirty-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.

Results

We 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.

Conclusions

Our 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

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

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

Human 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

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

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

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.
Evaluation of clinical threshold policies for cataract surgery among English commissioners
Authors: Coronini-Cronberg Sophie , Lee Henry , Darzi Ara , Smith Peter
Published: September 2012

Objectives:

To ascertain if access to cataract surgery is being restricted in England and to describe any explicit threshold criteria.

Methods:

A survey of 151 local commissioners to explore their cataract surgery policy. A literature review identified research evidence about thresholds for cataract surgery. A checklist was devised and applied to the policies supplied by commissioners.

Results:

Almost half (71/151) of commissioners were restricting access to surgery and this included patients with some capacity to benefit. There was wide variation in the scope and content of the 67 policies which were available for review. Almost all (92%) commissioners use criteria that do not reflect guidance or research evidence.

Conclusions:

Patients who could benefit from cataract surgery are being excluded by some commissioners. Variations in policy between commissioners results in inequalities in access.
Why patients need leaders: introducing a ward safety checklist
Authors: Amin Yogen , Grewcock Dave , Andrews Steve , Halligan Aidan
Published: September 2012

The safety and consistency of the care given to hospital inpatients has recently become a particular political and public concern. The traditional ‘ward round’ presents an obvious opportunity for systematically and collectively ensuring that proper standards of care are being achieved for individual patients. This paper describes the design and implementation of a ‘ward safety checklist’ that defines a set of potential risk factors that should be checked on a daily basis, and offers multidisciplinary teams a number of prompts for sharing and clarifying information between themselves, and with the patient, during a round. The concept of the checklist and the desire to improve ward rounds were well received in many teams, but the barriers to adoption were informative about the current culture on many inpatient wards. Although the ‘multidisciplinary ward round’ is widely accepted as good practice, the medical and nursing staff in many teams are failing to coordinate their workloads well enough to make multidisciplinary rounds a working reality. ‘Nursing’ and ‘medical’ care on the ward have become ‘de-coupled’ and the potential consequences for patient safety and good communication are largely self-evident. This problem is further complicated by a medical culture which values the primacy of clinical autonomy and as a result can be resistant to perceived attempts to ‘systematize’ medical care through instruments such as checklists.
A method for reliable voluntary oral administration of a fixed dosage (mg/kg) of chronic daily medication to rats
Authors: Corbett Adrian , McGowin Audrey , Sieber Scott , Flannery Tiffany , Sibbitt Bethany
Published: September 2012

Stress can influence a number of physiological processes including adult neurogenesis, metabolism, cardiovascular function, immune function, neurophysiological function, endocrine function and inflammatory processes following injury. In testing drugs which may be used to treat various diseases or injuries, reducing stress associated with chronic drug delivery to animal models should then be an imperative, which led us to design a reliable voluntary oral drug delivery method. Various drug combinations were tested versus vehicle controls in four different rat stocks or strains (Wistar, Fisher, Long Evans and Sprague Dawley) with our voluntary oral delivery system. Oral medications were placed into a store-bought sugar cookie dough ball (∼4 g), thoroughly integrating the dry drugs with the dough. This method has worked consistently to deliver the medication (complete ingestion) in four different stocks or strains of rats, with reliabilities ranging from 98.6% to 100%. The percentage of rats in each stock or strain that have at any time during the study had incomplete ingestion of the drugs ranged from 1% in Sprague Dawley, approximately 4% in Wistar and Fisher, to approximately 16% in Long Evans. Both serum and brain samples were analysed for high-performance liquid chromatography (HPLC) detection of one of our administered drugs: 5 mg/kg fluoxetine. HPLC analysis shows that serum levels are detectable 2–4 h after ingestion, but not 24 h after ingestion. Brain samples however, showed detectable levels of both fluoxetine and norfluoxetine more than a week following ingestion of a single dose, with higher norfluoxetine levels seen following a month of daily administered drugs.
The physiological impact of upper limb position in prone restraint
Authors: Barnett Richard , Hanson Paul , Stirling Chris , Pandyan Anand D
Published: September 2012

Deaths occurring during and/or in close proximity to physical restraint have been attributed to positional asphyxia. This study investigated the physiological impact of three recognized prone-restraint positions with participants remaining passive. Position 3 (P3) the supported prone position (SPP) was designed to reduce the extent of pressure on the anterior chest wall (PAC) by bringing the upper limbs underneath the shoulder joint whereas for the other two positions (P1 and P2) the arms were abducted from the torso. Twenty-five adults participated. Forced vital capacity (FVC), expiratory volume in one second (FEV1), heart rate (HR) and oxygen saturations (SpO2) were taken three times in an upright seated position (baseline) and in each prone position. Mean PAC was measured at 102.6 (±24.3) and 101.4 (±24.4) mmHg for P1 and P2, respectively; however, in the SPP (P3) the mean PAC pressure reduced to 72.7 (±16.9) mmHg. All three prone-restraint positions reduced FVC and FEV1 compared with baseline ( P < 0.001). P1 and P2 where the arms were abducted reduced respiratory measures equally but differed from the SPP position ( P < 0.001) where PAC was significantly lower. Reductions in FVC from baseline were 16% for P1 and P2, and 11% for the SPP (P3) where PAC was ∼28% lower than in P1 and P2. Reductions in FEV1 were similar in all three prone-restraint positions and HR and SpO2 were unaffected. In summary, all prone-restraint positions restrict respiratory function but the risk associated with the position reduces as the PAC reduces.
Solving Constrained Consumption–Investment Problems by Simulation of Artificial Market Strategies
Authors: Bick Björn , Kraft Holger , Munk Claus
Published: September 2012

Utility-maximizing consumption and investment strategies in closed form are unknown for realistic settings involving portfolio constraints, incomplete markets, and potentially a high number of state variables. Standard numerical methods are hard to implement in such cases. We propose a numerical procedure that combines the abstract idea of artificial, unconstrained complete markets, well-known closed-form solutions in affine or quadratic return models, straightforward Monte Carlo simulation, and a standard iterative optimization routine. Our method provides an upper bound on the wealth-equivalent loss compared to the unknown optimal strategy, and it facilitates our understanding of the economic forces at play by building on closed-form expressions for the strategies considered. We illustrate and test our method on the life-cycle problem of an individual who receives unspanned labor income and cannot borrow or short sell. The upper loss bound is small, and our method performs well in comparison with two existing methods.

This paper was accepted by Wei Xiong, finance.
Does More Time Spent Calling Home Correlate with Higher Remittances? Evidence from Migrants in the State of Qatar
Authors: Seshan Ganesh K.
Published: September 2012

This paper investigates an intriguing relationship between the demand for telecommunication and remittance services by migrants in Qatar. The hypothesis is that there are important synergies between telecommunications and remittances. Migrants with greater telecom access may have higher demand for remittances, because more frequent communication with relatives raises altruistic motivations for remitting. Migrants who remit more may also demand greater telecommunication service if they seek to monitor remittance recipients’ expenditure patterns. Suggestive evidence of complementarities in telecommunication and remittance demand is found using a cross-sectional dataset of temporary migrants in Qatar from developing countries. This finding highlights an overlooked, yet potentially important role of telecommunication in stimulating greater remittances.
Transient Receptor Potential Canonical Channels Regulate the Induction of Cerebellar Long-Term Depression
Authors: Chae Hong Goo , Ahn Sung Ji , Hong Yun Hwa , Chang Won Seok , Kim Jun , Kim Sang Jeong
Published: September 2012

In the cerebellum, synaptic strength at the synapses between parallel fibers and Purkinje cells is best known to be modulated via metabotropic glutamate receptor 1 (mGluR1)-dependent cerebellar long-term depression (LTD). An increase in intracellular calcium levels plays an important role in inducing mGluR1-dependent cerebellar LTD. Downstream of mGluR1, there are two major sources of calcium: transient receptor potential canonical (TRPC) channels and inositol trisphosphate receptors (IP3R). IP3R triggers a calcium release from the intracellular calcium store. Here, we show that TRPC channels mediate mGluR1-evoked slow currents to regulate cerebellar LTD in Sprague Dawley rats. We found that the inhibition of TRPC channels blocks the induction of cerebellar LTD. Moreover, we show that processes known to underlie cerebellar LTD induction, such as increases in intracellular calcium concentration, the activation of protein kinase C, and the internalization of GluR2, are also hindered by blocking TRPC. These results suggest that the mGluR1-evoked activation of TRPC channels is required for the induction of cerebellar LTD.
Members of the Myocyte Enhancer Factor 2 Transcription Factor Family Differentially RegulateBdnfTranscription in Response to Neuronal Depolarization
Authors: Lyons Michelle R. , Schwarz Charlotte M. , West Anne E.
Published: September 2012

Transcription of the gene encoding Brain-Derived Neurotropic Factor (BDNF) is induced in response to a wide variety of extracellular stimuli via the activation of a complex array of transcription factors. However, to what degree individual transcription factors confer specificity upon the regulation ofBdnfis poorly understood. Previous studies have shown that members of the myocyte enhancer factor 2 (MEF2) transcription factor family bind a regulatory element upstream ofBdnfpromoter I and associate with an unknown binding site inBdnfpromoter IV. Here we identify calcium-response element 1 as the MEF2 binding site in promoter IV of theBdnfgene and determine the requirements for individual MEF2 family members inBdnfregulation. MEF2A, MEF2C, and MEF2D are all highly expressed in embryonic rat cortical neurons; however, only theMef2cgene encodes an MEF2 splice variant that lacks the γ repressor-domain. We find that MEF2C variants lacking the γ-domain are particularly sensitive to activation by membrane depolarization, raising the possibility that the MEF2s may differentially contribute to activity-regulated gene expression. We find that only knockdown of MEF2C significantly impairs membrane depolarization-induced expression ofBdnfexon IV. By contrast, knockdown of MEF2D significantly enhanced depolarization-induced expression ofBdnfexon I. Together, these data show that individual members of the MEF2 family of transcription factors differentially regulate the expression ofBdnf, revealing a new mechanism that may confer specificity on the induction of this biologically important gene.
Activity-Dependent Regulation of Retinogeniculate Signaling by Metabotropic Glutamate Receptors
Authors: Govindaiah Gubbi , Wang Tongfei , Gillette Martha U. , Cox Charles L.
Published: September 2012

Thalamocortical neurons in dorsal lateral geniculate nucleus (dLGN) dynamically convey visual information from retina to the neocortex. Activation of metabotropic glutamate receptors (mGluRs) exerts multiple effects on neural integration in dLGN; however, their direct influence on the primary sensory input, namely retinogeniculate afferents, is unknown. In the present study, we found that pharmacological or synaptic activation of type 1 mGluRs (mGluR1s) significantly depresses glutamatergic retinogeniculate excitation in rat thalamocortical neurons. Pharmacological activation of mGluR1s attenuates excitatory synaptic responses in thalamocortical neurons at a magnitude sufficient to decrease suprathreshold output of these neurons. The reduction in both NMDA and AMPA receptor-dependent synaptic responses results from a presynaptic reduction in glutamate release from retinogeniculate terminals. The suppression of retinogeniculate synaptic transmission and dampening of thalamocortical output was mimicked by tetanic activation of retinogeniculate afferent in a frequency-dependent manner that activated mGluR1s. Retinogeniculate excitatory synaptic transmission was also suppressed by the glutamate transport blocker TBOA (dl-threo-β-benzyloxyaspartic acid), suggesting that mGluR1s were activated by glutamate spillover. The data indicate that presynaptic mGluR1contributes to an activity-dependent mechanism that regulates retinogeniculate excitation and therefore plays a significant role in the thalamic gating of visual information.
LIS1 Deficiency Promotes Dysfunctional Synaptic Integration of Granule Cells Generated in the Developing and Adult Dentate Gyrus
Authors: Hunt Robert F. , Dinday Matthew T. , Hindle-Katel William , Baraban Scott C.
Published: September 2012

Type I lissencephaly, a neuronal migration disorder characterized by cognitive disability and refractory epilepsy, is often caused by heterozygous mutations in the LIS1 gene. Histopathologies of malformation-associated epilepsies have been well described, but it remains unclear whether hyperexcitability is attributable to disruptions in neuronal organization or abnormal circuit function. Here, we examined the effect of LIS1 deficiency on excitatory synaptic function in the dentate gyrus of hippocampus, a region believed to serve critical roles in seizure generation and learning and memory. Mice with heterozygous deletion of LIS1 exhibited robust granule cell layer dispersion, and adult-born granule cells labeled with enhanced green fluorescent protein were abnormally positioned in the molecular layer, hilus, and granule cell layer. In whole-cell patch-clamp recordings, reduced LIS1 function was associated with greater excitatory synaptic input to mature granule cells that was consistent with enhanced release probability at glutamatergic synapses. Adult-born granule cells that were ectopically positioned in the molecular layer displayed a more rapid functional maturation and integration into the synaptic network compared with newborn granule cells located in the hilus or granule cell layer or in wild-type controls. In a conditional knock-out mouse, induced LIS1 deficiency in adulthood also enhanced the excitatory input to granule cells in the absence of neuronal disorganization. These findings indicate that disruption of LIS1 has direct effects on excitatory synaptic transmission independent of laminar disorganization, and the ectopic position of adult-born granule cells within a malformed dentate gyrus critically influences their functional maturation and integration.
Distinct Information Representation and Processing for Goal-Directed Behavior in the Dorsolateral and Ventrolateral Prefrontal Cortex and the Dorsal Premotor Cortex
Authors: Yamagata Tomoko , Nakayama Yoshihisa , Tanji Jun , Hoshi Eiji
Published: September 2012

Although the lateral prefrontal cortex (lPFC) and dorsal premotor cortex (PMd) are thought to be involved in goal-directed behavior, the specific roles of each area still remain elusive. To characterize and compare neuronal activity in two sectors of the lPFC [dorsal (dlPFC) and ventral (vlPFC)] and the PMd, we designed a behavioral task for monkeys to explore the differences in their participation in four aspects of information processing: encoding of visual signals, behavioral goal retrieval, action specification, and maintenance of relevant information. We initially presented a visual object (an instruction cue) to instruct a behavioral goal (reaching to the right or left of potential targets). After a subsequent delay, a choice cue appeared at various locations on a screen, and the animals could specify an action to achieve the behavioral goal. We found that vlPFC neurons amply encoded object features of the instruction cues for behavioral goal retrieval and, subsequently, spatial locations of the choice cues for specifying the actions. By contrast, dlPFC and PMd neurons rarely encoded the object features, although they reflected the behavioral goals throughout the delay period. After the appearance of the choice cues, the PMd held information for action throughout the specification and preparation of reaching movements. Remarkably, lPFC neurons represented information for the behavioral goal continuously, even after the action specification as well as during its execution. These results indicate that area-specific representation and information processing at progressive stages of the perception–action transformation in these areas underlie goal-directed behavior.
Selective Corticospinal Tract Injury in the Rat Induces Primary Afferent Fiber Sprouting in the Spinal Cord and Hyperreflexia
Authors: Tan Andrew M. , Chakrabarty Samit , Kimura Hiroki , Martin John H.
Published: September 2012

The corticospinal tract (CST) has dense contralateral and sparse ipsilateral spinal cord projections that converge with proprioceptive afferents on common spinal targets. Previous studies in adult rats indicate that the loss of dense contralateral spinal CST connections after unilateral pyramidal tract section (PTx), which models CST loss after stroke or spinal cord injury, leads to outgrowth from the spared side into the affected, ipsilateral, spinal cord. The reaction of proprioceptive afferents after this CST injury, however, is not known. Knowledge of proprioceptive afferent responses after loss of the CST could inform mechanisms of maladaptive plasticity in spinal sensorimotor circuits after injury. Here, we hypothesize that the loss of the contralateral CST results in a reactive increase in muscle afferents from the impaired limb and enhancement of their physiological actions within the cervical spinal cord. We found that 10 d after PTx, proprioceptive afferents sprout into cervical gray matter regions denervated by the loss of CST terminations. Furthermore, VGlut1-positive boutons, indicative of group 1A afferent terminals, increased on motoneurons. PTx also produced an increase in microglial density within the gray matter regions where CST terminations were lost. These anatomical changes were paralleled by reduction in frequency-dependent depression of the H-reflex, suggesting hyperreflexia. Our data demonstrate for the first time that selective CST injury induces maladaptive afferent fiber plasticity remote from the lesion. Our findings suggest a novel structural reaction of proprioceptive afferents to the loss of CST terminations and provide insight into mechanisms underlying spasticity.
Effects of species differences on oocyte regulation of granulosa cell function
Authors: Lin Jia Yi , Pitman-Crawford Janet L , Bibby Adrian H , Hudson Norma L , McIntosh C Joy , Juengel Jennifer L , McNatty Kenneth P
Published: September 2012

The aims were to investigate whether oocyte-secreted growth factors from a high (i.e. rat) and low (i.e. sheep) ovulation rate species could stimulate 3H-thymidine incorporation in granulosa cells (GC) from antral follicles from the same or across species. Denuded oocytes (DO) were co-incubated with GC with or without specific antibodies to growth differentiating factor 9 (GDF9) or bone morphogenetic protein 15 (BMP15). Co-incubations of DO-GC from the same or across species significantly increased thymidine incorporation in GC with increasing numbers of DO. GDF9 immuno-neutralisation reduced thymidine incorporation in rat GC co-incubated with either rat or ovine DO and in ovine GC co-incubated with ovine or rat DO. BMP15 immuno-neutralisation only reduced thymidine incorporation when ovine DO were co-incubated with either ovine or rat GC. Western blotting of oocytes co-incubated with GC identified GDF9 and BMP15 proteins for sheep and GDF9 protein for rats in oocyte lysates and incubation media. With respect to rat BMP15, a promature protein was identified in the oocyte lysate but not in media. Expression levels of GDF9 relative to BMP15 mRNA in DO co-incubated with GC were highly correlated (R
2=0.99) within both species. However, the expression ratios were markedly different for the rat and sheep (4.3 vs 1.0 respectively). We conclude that during follicular development, rat oocytes secrete little, if any, BMP15 and that GDF9 without BMP15 can stimulate proliferation of rat and ovine GC. In contrast, ovine oocytes secrete both BMP15 and GDF9, and both were found to stimulate proliferation in ovine and rat GC.
Sôbre a expressão hr1 + kr2 + Ir3 = 0
Authors: Salgado Eduardo A.
Published: September 2012

Por meio da projeção estereográfica e geometria analítica é apresentada uma nova dedução da expressão hr1 + kr2 + lr3 = 0.
Sôbre uma modificação no método de Neubauer
Authors: Catani R. A. , Bergamin Filho H.
Published: September 2012

O presente trabalho relata os dados obtidos, segundo uma modificação do método de Neubauer, comparados aos obtidos pelo método usual do citado autor. A modificação consistiu no uso de cristalizadores menores e no emprêgo de um número de plantas e de um pêso de terra muito menores. Assim, foram colocadas 25 sementes de arroz em 20 g de terra, intimamente misturadas com 40 g de areia de praia lavada, em cristalizadores de 80 mm de diâmetro, por 20 mm de altura. Decorridos 18 dias após a germinação, as plantas foram colhidas, incineradas e o potássio foi determinado por fotômetro de chama. Os resultados foram comparados com os dados obtidos através de um experimento feito com as mesmas amostras de terra e no mesmo tempo, conforme a técnica usual de Neubauer. Praticamente, os dois métodos se equivalem, conforme mostram os dados do quadro 1 em Resultados e Discussão. As principais vantagens do método modificado, em relação ao método usual de Neubauer, podem ser resumidas nas seguintes: redução do pêso da amostra de 100 para 20 g e redução do pêso da areia de praia lavada de 350 para 70 g; redução da área ocupada pelos cristalizadores para menos de um terço; redução do número de plantas para um quarto (de 100 para 25 plantas) e redução do trabalho exigido para a execução do método, desde o preparo dos cristalizadores, até o preparo das plantas, incineração e análise.