bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibacterial constituents of three Cameroonian medicinal plants: Garcinia nobilis, Oricia suaveolens and Balsamocitrus camerunensis
Authors: Fouotsa Hugues , Mbaveng Armelle T , Mbazoa Celine D , Nkengfack Augustin E , Farzana Shaheen , Iqbal Choudhary M , Marion Meyer Jacobus J , Lall Namrita , Kuete Victor
Published: April 2013

Background

Multidrug resistance is a worrying cause of treatment failure in bacterial infections. The search of bioactive constituents from medicinal plants against multidrug resistant (MDR) bacteria has significantly evolved in the two last decades. In the present study, twenty-two compounds (three terpenoids, eleven phenolics and eight alkaloids) isolated from three Cameroonian medicinal plants, namely Garcinia nobilis, Oricia suaveolens and Balsamocitrus camerunensis, as well as the crude extracts were tested for their antibacterial activities against Mycobacterium tuberculosis and Gram-negative bacteria amongst which were MDR active efflux pumps expressing phenotypes.

Methods

The microplate alamar blue assay (MABA) and the broth microdilution methods were used to determine the minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) of the studied samples.

Results

The results of the MIC determinations indicate that, the best crude extract was that from G. nobilis (GNB), its inhibitory effects being noted against 12 of the 14 tested bacteria. The extract of GNB also exhibited better anti-tuberculosis (MIC of 128 μg/ml M. tuberculosis against ATCC 27294 strain) and antibacterial (MIC of 64 μg/ml against Escherichia coli ATCC10536) activities compared to the extracts of O. suaveolens and B. camerunensis. Interestingly, 4-prenyl-2-(3,7-dimethyl-2,6-octadienyl)-1,3,5,8-tetrahydroxyxanthone (2), isolated from the most active extract GNB, also showed the best activity amongst compounds, inhibiting the growth of all the fourteen tested microorganisms. The lowest MIC value obtained with compound 2 was 8 μg/ml against M. tuberculosis ATCC 27294 and M. tuberculosis clinical MTCS2 strains. Other compounds showed selective activities with 11 of the 14 tested bacteria being sensitive to the xanthone, morusignin I (5) and the alkaloid, kokusaginine (13).

Conclusions

The results of the present investigation provide evidence that the crude extract from G. nobilis, O. suaveolens and B. camerunensis as well as some of their compounds, and mostly compound 2 (isolated from G. nobilis,) could be considered as interesting natural antibacterial products.
Daily life and life quality 3 years following prostate cancer treatment
Authors: Jakobsson Liselotte , Persson Lena , Lundqvist Pia
Published: April 2013

Background

Knowledge of experiences from prostate cancer is sparse in a longitudinal perspective. From a nursing perspective, results from combined qualitative and quantitative studies are lacking however would present the broadest knowledge base for best practice. Present descriptions of medical-physical symptoms such as urinary, bowel and sexual dysfunction from quantitative inquiries need be complemented with qualitative results. Such knowledge is essential in relation to treatment and communication with patients over the years and not only shortly after surgery.

Methods

A longitudinal study was formatted to investigate general and specific health quality and sense of coherence quantitative alterations over three years. A general health quality module (EORTC QLC-C30) and a disease-specific module (EORTC PR-25) were applied for the longitudinal study together with the Orientation to life questionnaire (SOC), measuring a persons’ sense of coherence. In order to strengthen reliability and compensate for low participation we used the Directed content analysis for interviewing and analysis. The method allows using findings from earlier research when interviewing along with detecting new areas. Twenty-one men were followed over three years and six of them, in the third year, accepted to be interviewed.

Results

We found high quality of life ratings and extended the study with follow-up interviews in year three, to investigate whether questionnaire results were in line with interview findings. We found high life quality and functioning ratings that were in line with qualitative descriptions. Interview analysis showed retrieval of life as lived before, yet in a different way, the men never forgot the diagnosis event, had a unique illness history worth hearing, and had come to terms with most treatment-related shortcomings. Sense of coherence ratings were medium to high and confirmed stability over time in comprehensibility, manageability and meaningfulness after prostate cancer treatment.

Conclusions

Over the years, the men’s negative experiences from shifted into ‘a good life’ though in a different way than before. The interpretation is supported in the study by quantitative results showing a high degree of functioning. The men’s sense of coherence seamed to support their handling of life three years after prostate cancer treatment.
Preferential transfer of mitochondria from endothelial to cancer cells through tunneling nanotubes modulates chemoresistance
Authors: Pasquier Jennifer , Guerrouahen Bella S , Al Thawadi Hamda , Ghiabi Pegah , Maleki Mahtab , Abu-Kaoud Nadine , Jacob Arthur , Mirshahi Massoud , Galas Ludovic , Rafii Shahin , Le Foll Frank , Rafii Arash
Published: April 2013

Our vision of cancer has changed during the past decades. Indeed tumors are now perceived as complex entities where tumoral and stromal components interact closely. Among the different elements of tumor stroma the cellular component play a primordial role. Bone Marrow derived mesenchymal cells (MSCs) are attracted to tumor sites and support tumor growth. Endothelial cells (ECs) play a major role in angiogenesis. While the literature documents many aspects of the cross talk between stromal and cancer cells, the role of direct hetero-cellular contact is not clearly established. Recently, Tunneling nanotubes (TnTs) have been shown to support cell-to-cell transfers of plasma membrane components, cytosolic molecules and organelles within cell lines. Herein, we have investigated the formation of heterocellular TnTs between stromal (MSCs and ECs) and cancer cells. We demonstrate that TnTs occur between different cancer cells, stromal cells and cancer-stromal cell lines. We showed that TnTs-like structure occurred in 3D anchorage independent spheroids and also in tumor explant cultures. In our culture condition, TnTs formation occurred after large membrane adhesion. We showed that intercellular transfers of cytoplasmic content occurred similarly between cancer cells and MSCs or ECs, but we highlighted that the exchange of mitochondria occurred preferentially between endothelial cells and cancer cells. We illustrated that the cancer cells acquiring mitochondria displayed chemoresistance. Our results illustrate the perfusion-independent role of the endothelium by showing a direct endothelial to cancer cell mitochondrial exchange associated to phenotypic modulation. This supports another role of the endothelium in the constitution of the metastatic niche.
Fractional complex transform method for wave equations on Cantor sets within local fractional differential operator
Authors: Su Wei-Hua , Yang Xiao-Jun , Jafari H , Baleanu Dumitru
Published: April 2013

This paper points out the fractional complex transform method for wave equations on Cantor sets within the local differential fractional operators. The proposed method is efficient to handle differential equations on Cantor sets.
Gelsolin activity controls efficient early HIV-1 infection
Authors: García-Expósito Laura , Ziglio Serena , Barroso-González Jonathan , de Armas-Rillo Laura , Valera María-Soledad , Zipeto Donato , Machado José-David , Valenzuela-Fernández Agustín
Published: April 2013

Background

HIV-1 entry into target lymphocytes requires the activity of actin adaptors that stabilize and reorganize cortical F-actin, like moesin and filamin-A. These alterations are necessary for the redistribution of CD4-CXCR4/CCR5 to one pole of the cell, a process that increases the probability of HIV-1 Envelope (Env)-CD4/co-receptor interactions and that generates the tension at the plasma membrane necessary to potentiate fusion pore formation, thereby favouring early HIV-1 infection. However, it remains unclear whether the dynamic processing of F-actin and the amount of cortical actin available during the initial virus-cell contact are required to such events.

Results

Here we show that gelsolin restructures cortical F-actin during HIV-1 Env-gp120-mediated signalling, without affecting cell-surface expression of receptors or viral co-receptor signalling. Remarkably, efficient HIV-1 Env-mediated membrane fusion and infection of permissive lymphocytes were impaired when gelsolin was either overexpressed or silenced, which led to a loss or gain of cortical actin, respectively. Indeed, HIV-1 Env-gp120-induced F-actin reorganization and viral receptor capping were impaired under these experimental conditions. Moreover, gelsolin knockdown promoted HIV-1 Env-gp120-mediated aberrant pseudopodia formation. These perturbed-actin events are responsible for the inhibition of early HIV-1 infection.

Conclusions

For the first time we provide evidence that through its severing of cortical actin, and by controlling the amount of actin available for reorganization during HIV-1 Env-mediated viral fusion, entry and infection, gelsolin can constitute a barrier that restricts HIV-1 infection of CD4+ lymphocytes in a pre-fusion step. These findings provide important insights into the complex molecular and actin-associated dynamics events that underlie early viral infection. Thus, we propose that gelsolin is a new factor that can limit HIV-1 infection acting at a pre-fusion step, and accordingly, cell-signals that regulate gelsolin expression and/or its actin-severing activity may be crucial to combat HIV-1 infection.
Influence of emulsifiers on the characteristics of polyurethane structures used as drug carrier
Authors: Heghes Alina , Soica Codruta M , Ardelean Simona , Ambrus Rita , Muntean Danina , Galuscan Atena , Dragos Dan , Ionescu Daniela , Borcan Florin
Published: April 2013

Background

Emulsifiers have a significant role in the emulsion polymerization by reducing the interfacial tension thus increasing the stability of colloidal dispersions of polymer nanostructures. This study evaluates the impact of four emulsifiers on the characteristics of polyurethane hollow structures used as drug delivery system.

Results

Polyurethane (PU) structures with high stability and sizes ranging from nano- to micro-scale were obtained by interfacial polyaddition combined with spontaneous emulsification. The pH of PU aqueous solutions (0.1% w/w) was slightly acidic, which is acceptable for products intended to be used on human skin. Agglomerated structures with irregular shapes were observed by scanning electron microscopy. The synthesized structures have melting points between 245-265°C and reveal promising results in different evaluations (TEWL, mexametry) on murine skin.

Conclusions

In this study hollow PU structures of reduced noxiousness were synthesized, their size and stability being influenced by emulsifiers. Such structures could be used in the pharmaceutical field as future drug delivery systems.
Potential role of N-carbamoyl glutamate in biosynthesis of arginine and its significance in production of ruminant animals
Authors: Chacher Bahram , Liu Hongyun , Wang Diming , Liu Jianxin
Published: April 2013

Arginine (ARG) exerts many beneficial effects on animal body and enhanced angiogenesis, lactogenesis, which finally leads to the improvement in nitrogen (N) metabolism, reproduction, lactation, immunity and growth. Unfortunately, unprotected ARG will be degraded in the rumen and its price is high, thus feeding rumen-protected ARG seems to be uneconomical. Alternatively, N-carbamoyl glutamate (NCG) is structural analogue of N-acetyl glutamate, cofactor of cabamoyl phosphate synthetase1, is lower in rumen degradation compared to ARG. Additionally, rumen epithelial and duodenal cells have potentially utilized the NCG for ureagenesis. Supplementation of NCG to high yielding dairy cows increased plasma concentration of ARG and nitric oxide, decreased the plasma ammonia N and improved lactation performance and N utilization. Supplementation of NCG enhanced pregnancy rates in rats, improved litter size and fetal survival rate, thereby improved the reproductive performance of sows. Oral NCG supplementation increases plasma ARG and somatotropin levels, and increased growth rate and muscle protein synthesis in nursing piglets. The NCG is potential a relatively cheaper source of feed additive to offer vital compensation over oral administration of ARG, resulting in improved ruminant animal health and production. In this article, we reviewed the mechanism of ARG biosynthesis by NCG and their significance in growth, reproduction, milk production and N utilization in ruminant animals.
Halomonas sp. BS4, A biosurfactant producing halophilic bacterium isolated from solar salt works in India and their biomedical importance
Authors: Donio Mariathason Birdilla Selva , Ronica Fernando Arul , Viji Vijayaragavan Thanga , Velmurugan Subramanian , Jenifer John Selesteen Charles Adlin , Michaelbabu Mariavincent , Dhar Prasenjit , Citarasu Thavasimuthu
Published: April 2013

Halophilic bacteria were isolated from Thamaraikulam solar salt works in India. After routine biosurfactant screening by various methods, the biosurfactant producing bacteria, Halomonas sp BS4 was confirmed by 16 S rRNA sequencing. The growth optimization of Halomonas sp BS4 revealed their optimum growth at 8% NaCl and 6-8 pH in the growth medium. Further the partially purified biosurfactants were characterized by TLC, FTIR and GC-MS analysis. GC-MS results revealed that, the partial purified biosurfactants contain 1, 2-Ethanediamine N, N, N’, N’-tetra, 8-Methyl-6-nonenamide, (Z)-9-octadecenamide and a fatty acid derivative. Pharmacological screening of antibacterial, antifungal, antiviral and anticancer assays revealed that, the biosurfactant extracted from Halomonas sp BS4 effectively controlled the human pathogenic bacteria and fungi an aquaculturally important virus, WSSV. The biosurfactant also suppressed the proliferation of mammary epithelial carcinoma cell by 46.77% at 2.5 μg concentration. Based on these findings, the present study concluded that, there is a possibility to develop eco-friendly antimicrobial and anticancer drugs from the extremophilic origin.
A review on electronic and optical properties of silicon nanowire and its different growth techniques
Authors: Hasan Mehedhi , Huq Md Fazlul , Mahmood Zahid Hasan
Published: April 2013

Electronic and optical properties of Silicon Nanowire (SiNW) obtained from theoretical studies and experimental approaches have been reviewed. The diameter dependency of bandgap and effective mass of SiNW for various terminations have been presented. Optical absorption of SiNW and nanocone has been compared for different angle of incidences. SiNW shows greater absorption with large range of wavelength and higher range of angle of incidence. Reflectance of SiNW is less than 5% over majority of the spectrum from the UV to near IR region. Thereafter, a brief description of the different growth techniques of SiNW is given. The advantages and disadvantages of the different catalyst materials for SiNW growth are discussed at length. Furthermore, three thermodynamic aspects of SiNW growth via the vapor–liquid–solid mechanism are presented and discussed.
The effect of confining pressure on elastic wave velocities and dynamic to static Young’s modulus ratio
Authors: Asef Mohammad Reza , Najibi Ali Reza
Published: April 2013

We carried out laboratory experiments under dry conditions on limestone core specimens of Sarvak formation obtained from an oil well in the southwest of Iran. Our objective was to study the effect of confining pressure on the compressional and shear wave velocities ([Formula: see text], [Formula: see text]), and on the dynamic to static Young’s modulus ratio ([Formula: see text]). Furthermore, we made attempts to predict [Formula: see text] and [Formula: see text] at atmospheric pressure based on the same velocities at various confining pressures. These analyses revealed that, below a critical pressure with an increase in confinement [Formula: see text] and [Formula: see text] increased exponentially, representing a poroelastic regime. Above a critical pressure, however, the trend was linear. Likewise, we observed that with an increase in confinement, [Formula: see text] initially decreased exponentially, followed by a linear decreasing trend above the critical pressure. This indicated that [Formula: see text] is more responsive than [Formula: see text]. Accordingly, these observations infer that it is possible to predict [Formula: see text] based on [Formula: see text] at different confining stresses. This is an important improvement for geomechanical modeling of hydrocarbon and geothermal reservoirs because static parameters are more realistic input parameters. Besides, we derived the coefficients of the velocity-pressure equation for Sarvak limestone using least square regression analysis. More interestingly, we predicted [Formula: see text] and [Formula: see text] at atmospheric pressure based on these coefficients. Good agreement was observed between measured and predicted velocities at atmospheric pressure. Analysis of similar published experiments on oceanic basalts strongly confirmed these observations.
Septins 2, 7, and 9 and MAP4 co-localize along the axoneme in the primary cilium and control ciliary length
Authors: Ghossoub Rania , Hu Qicong , Failler Marion , Rouyez Marie-Christine , Spitzbarth Benjamin , Mostowy Serge , Wolfrum Uwe , Saunier Sophie , Cossart Pascale , Nelson W. James , Benmerah Alexandre
Published: April 2013

Septins are a large, evolutionarily conserved family of GTPases that form hetero-oligomers and interact with the actin-based cytoskeleton and microtubules. They are involved in scaffolding functions, and form diffusion barriers in budding yeast, the sperm flagellum and the base of primary cilia of kidney epithelial cells. We investigated the role of septins in the primary cilium of retinal pigmented epithelial (RPE) cells, and found that SEPT2 forms a 1∶1∶1 complex with SEPT7 and SEPT9 and that the three members of this complex co-localize along the length of the axoneme. Similar to observations in kidney epithelial cells, depletion of cilium-localized septins by siRNA-based approaches inhibited ciliogenesis. MAP4, which is a binding partner of SEPT2 and controls the accessibility of septins to microtubules, was also localized to the axoneme where it appeared to negatively regulate ciliary length. Taken together, our data provide new insights into the functions and regulation of septins and MAP4 in the organization of the primary cilium and microtubule-based activities in cells.
BBS7 is required for BBSome formation and its absence in mice results in Bardet-Biedl syndrome phenotypes and selective abnormalities in membrane protein trafficking
Authors: Zhang Qihong , Nishimura Darryl , Vogel Tim , Shao Jianqiang , Swiderski Ruth , Yin Terry , Searby Charles , Carter Calvin C. , Kim GunHee , Bugge Kevin , Stone Edwin M. , Sheffield Val C.
Published: April 2013

Bardet-Biedl Syndrome (BBS) is a pleiotropic and genetically heterozygous disorder caused independently by numerous genes (BBS1-BBS17). Seven highly conserved BBS proteins (BBS1, 2, 4, 5, 7, 8, and 9) form a complex known as the BBSome, which functions in ciliary membrane biogenesis. BBS7 is both a unique subunit of the BBSome and displays direct physical interaction with a second BBS complex, the BBS chaperonin complex. To examine the in vivo function of BBS7, we generated Bbs7 knockout mice. Bbs7−/− mice show similar phenotypes to other BBS gene mutant mice including retinal degeneration, obesity, ventriculomegaly, and male infertility characterized by abnormal spermatozoa flagellar axonemes. Using tissues from Bbs7−/− mice, we show that BBS7 is required for BBSome formation, and that BBS7 and BBS2 depend on each other for protein stability. Although the BBSome serves as a coat complex for ciliary membrane proteins, BBS7 is not required for the localization of ciliary membrane proteins polycystin-1, polycystin-2, or bitter taste receptors, but absence of BBS7 leads to abnormal accumulation of the dopamine D1 receptor (D1R) to the ciliary membrane, indicating that BBS7 is involved in specific membrane protein localization to cilia.
Ubiquitination of PIPKIγ90 by HECTD1 regulates focal adhesion dynamics and cell migration
Authors: Li Xiang , Zhou Qi , Sunkara Manjula , Kutys Matthew L. , Wu Zhaofei , Rychahou Piotr , Morris Andrew J. , Zhu Haining , Evers B. Mark , Huang Cai
Published: April 2013

PIPKIγ90 binds talin and localizes at focal adhesions (FAs). PIP2 generated by PIPKIγ90 is essential for FA formation and cell migration. On the other hand, PIPKIγ90 and the β integrin tail compete for overlapping binding sites on talin. Enhanced PIPKIγ90-talin interaction suppresses talin binding to the β integrin. It is unknown how PIPKIγ90 is removed from the PIPKIγ90-talin complex after on-site PIP2 production during cell migration. Here we show that PIPKIγ90 is a substrate for HECTD1, an E3 ubiquitin ligase regulating cell migration. HECTD1 ubiquitinated PIPKIγ90 at Lys97 and resulted in PIPKIγ90 degradation. Expression of PIPKIγ90K97R enhanced PIP2 and PIP3 production and inhibited FA assembly and disassembly, cancer cell migration, invasion and metastasis. Interestingly, mutation at Trp647 abolished the inhibition of PIPKIγ90K97R on FA dynamics and partially rescued cancer cell migration and invasion. Thus, cycling PIPKIγ90 ubiquitination by HECTD1 and consequent degradation remove PIPKIγ90 from talin after on-site PIP2 production, providing an essential regulatory mechanism for FA dynamics and cell migration.
Intramolecular shielding maintains STIM1 in an inactive conformation
Authors: Yu Fang , Sun Lu , Hubrack Satanay , Selvaraj Senthil , Machaca Khaled
Published: April 2013

Store-Operated Calcium Entry (SOCE) represents a major calcium influx pathway in non-excitable cells and is central to many physiological processes such as T-cell activation and mast cell degranulation. SOCE is activated through intricate coordination between the Ca2+ sensor on the ER membrane (STIM1) and the plasma membrane channel Orai1. When Ca2+ stores are depleted, STIM1 oligomerizes and physically interacts with Orai1 through its SOAR/CAD domain resulting in Orai1 gating and Ca2+ influx. Here we engineer novel inter- and intra-molecular FRET sensors in the context of the full-length membrane anchored STIM1, and show that STIM1 undergoes a conformational change in response to store depletion to adopt a stretched ‘open’ conformation that exposes SOAR/CAD allowing it to interact with Orai1. Mutational analyses reveal that electrostatic interactions between the predicted 1st and 3rd coiled-coil domains of STIM1 are not involved in maintaining the ‘closed’ inactive conformation. In addition, they argue that an amphipathic α-helix between residues 317–336 in the so-called inhibitory domain is important to maintain STIM1 in a closed conformation at rest. Indeed mutations that alter the amphipathic properties of this helix result in a STIM1 variant that is unable to respond to store depletion in terms of forming puncta, translocation to the cortical ER or activating Orai1.
Novel role of microRNA146b in promoting mammary alveolar progenitor cell maintenance
Authors: Elsarraj Hanan S. , Hong Yan , Valdez Kelli , Carletti Martha , Salah Sally M. , Raimo Monica , Taverna Daniela , Prochasson Philippe , Bharadwaj Uddalak , Tweardy David J. , Christenson Lane K. , Behbod Fariba
Published: April 2013

Here, we have shown that miR146b promotes the maintenance of pregnancy derived mammary luminal alveolar progenitors. MiR146b expression was significantly higher in the mammary glands of pregnant and lactating mice compared to virgin. Furthermore, miR146b levels were significantly higher in the mouse mammary glands exposed to sex hormones, estrogen plus progesterone compared to untreated control animals. Pregnancy derived primary mouse mammary epithelial cells, knocked down of miR146b showed a significant reduction in the number of hollow acinar organoid structures formed on 3D Matrigel and in β-casein expression. This demonstrates that miR146b promotes the maintenance of pregnancy derived mammary luminal alveolar progenitors. It has been shown that mouse mammary luminal progenitors give rise to hollow organoid structures while solid organoid structure are derived from stem cells. Among several of miR146b targets, miR146b knockdown resulted in preferential STAT3β overexpression. In the primary mouse mammary epithelial cells, overexpression of STAT3β isoform caused mammary epithelial cells death and a significant reduction in β-casein mRNA expression. Therefore, we conclude that, during pregnancy, miR146b is involved in luminal alveolar progenitor cell maintenance by, at least partially, regulating STAT3β.
Dose- and time-dependent effects of lipopolysaccharide on technetium-99-m-labeled diethylene-triamine pentaacetatic acid clearance, respiratory system mechanics and pulmonary inflammation
Authors: Kastis George A , Toumpanakis Dimitrios , Loverdos Konstantinos , Anaplioti Aikaterini , Samartzis Alexandros , Argyriou Pinelopi , Loudos George , Karavana Vassiliki , Tzouda Vassiliki , Datseris Ioannis , Rontogianni Demetra , Roussos Charalampos , Theocharis Stamatios E , Vassilakopoulos Theodoros
Published: April 2013

Intratracheal administration of lipopolysaccharide (LPS) in animals is a commonly used model of acute lung injury, characterized by increased alveolar-capillary membrane permeability causing protein-rich edema, inflammation, deterioration of lung mechanical function and impaired gas exchange. Technetium-99-m-labeled diethylene-triamine pentaacetatic acid (99mTc-DTPA) scintigraphy is a non-invasive technique to assess lung epithelial permeability. We hypothesize that the longer the exposure and the higher the dose of LPS the greater the derangement of the various indices of lung injury. After 3, 6 and 24 h of 5 or 40 μg LPS intratracheally administration, 99mTc-DTPA was instilled in the lung. Images were acquired for 90 min with a γ-camera and the radiotracer clearance was estimated. In another subgroup, the mechanical properties of the respiratory system were estimated with the forced oscillation technique and static pressure-volume curves, 4.5, 7.5 and 25.5 h post-LPS (iso-times with the end of 99mTc-DTPA scintigraphy). Bronchoalveolar lavage (BAL) was performed and a lung injury score was estimated by histology. Lung myeloperoxidase (MPO) activity was measured. 99mTc-DTPA clearance increased in all LPS challenged groups compared with control. DTPA clearance presented a U-shape time course at the lower dose, while LPS had a declining effect over time at the larger dose. At 7.5 and 25.5 h post-LPS, tissue elasticity was increased and static compliance decreased at both doses. Total protein in the BAL fluid increased at both doses only at 4.5 h Total lung injury score and MPO activity were elevated in all LPS-treated groups. There is differential time- and dose-dependency of the various indices of lung injury after intratracheally LPS instillation in rats.
The virus inoculum volume influences outcome of influenza A infection in mice
Authors: Miller Darren S , Kok Tuckweng , Li Peng
Published: April 2013

When establishing animal models of viral respiratory infection, the optimal dose and route of delivery are critical to ensure reproducible outcomes. The mouse model for influenza infection is widely used due to the small animal size and simplicity of viral inoculation. During establishment of a mouse model of influenza A infection we observed a marked shift in morbidity when identical influenza A inoculum doses were delivered in less than 35 μL. We show for the first time that mice challenged with a 25 μL inoculum volume readily recovered following infection with an infectious dose of influenza A virus that was fatal when inoculated in 35 or 50 μL volumes.
Türk Din Mûsikîsi’nde Salâ (Salât) Formu ve Salâ Besteleri
Authors: Harmancı Başak İlhan
Published: April 2013

“Duâ, temcîd” mânâlarına gelen Muhammed (sav)'e Allah'tan rahmet dilemek, ona sığınmak, onu ve aile fertlerini Muhammed (sav)'e Allah'tan rahmet dilemek, ona sığınmak, onu ve aile fertlerini hürmetle anmak, şefâatını istemek maksadıyla yazılmış duâ cümleleriyle sevgi ve hürmetle anmak, şefâatını istemek maksadıyla yazılmış duâ cümleleriyle sevgi ve övgü ifade eden sözlerin bazen bir beste bazen de serbeokunduğu Türk Din Mûsikîsi formlarından biridir.Teâla’nın emri, gerek Hz. Peygamber (s.a.v.)’e salât ü selâm getirmenin faziletleri Teâla’nın emri, gerek Hz. Peygamber (s.a.v.)’e salât ü selâm getirmenin faziletleri hakkındaki hadîs-i şerîfleri ve bunlara ilâveten ümmetinin sevgi ve hürmeti pek çok salât ü selâm metninin yazılmasına sebeb olmuştur.amacı bestelenmiş olan salâ metinlerini bir araya getirerek Türk Din Mûsikîsi salâ amacı bestelenmiş olan salâ metinlerini bir araya getirerek Türk Din Mûsikîsi salâ repertuarını ortaya koymak ve salâ formu hakkında detaylı bilgi vermektir.
‘If a Picture Paints a Thousand Words’: The Development of Human Identification Techniques in Forensic Anthropology and Their Implications for Human Rights in the Criminal Process
Authors: Ferguson Pamela R. , Raitt Fiona E.
Published: April 2013

Newly developed techniques in forensic anthropology offer great potential to assist in identifying, and ultimately convicting, perpetrators of serious sexual assaults, particularly those involving young children. They can also facilitate the prosecution of those who create and disseminate child pornography. They do, however, require that photographs be taken of suspects' hands, and sometimes their genitals. This article explores the human rights implications which arise from the intrusive procedures needed to obtain the photographs necessary for comparative purposes. It assesses police powers; the rights of suspects to privacy and bodily integrity; the privilege against compelled self-incrimination; and the right to legal advice, and addresses the question: what are the permissible limits of intrusive searches?
First Time Lucky? Exploring Whether First-Time Offenders Should Be Sentenced More Leniently
Authors: Freer Elaine
Published: April 2013

This article explores the normative position and theoretical justifications for sentencing first-time offenders more leniently than repeat offenders, and examines whether such a practice is defensible. Those justifications include a lack of awareness of the gravity of criminal behaviour, a single lapse, that no censure has previously been communicated by the criminal justice system to that person, adolescent-limited offending, the impact of being in a minority group, and non-uniform impact. It examines whether various sentencing philosophies support sentence reductions for first-time offenders, and whether the justifiability of such practices depends on the theoretical basis and aims of sentencing, for instance the role of proportionality and deterrence.
The new world of organic reactions in water
Authors: Kobayashi Shū
Published: April 2013

Different reactivities and selectivities are observed in water compared with those in organic solvents. In this article, such three examples are described. While ammonia was known not to react in metal-catalyzed allylic amination, palladium-catalyzed allylic amination using aqueous ammonia proceeded to afford primary amines in high yields. Second, allylboronates reacted with aldehydes in aqueous media to afford α-addition adducts exclusively in high yields with high diastereo- and enantioselectivities using Zn(OH)2with ligands as catalysts. Finally, it was found that catalytic use of In(0) was effective for the reactions of allylboronates with ketones in water.
Opioid Modulation of Ventral Pallidal Afferents to Ventral Tegmental Area Neurons
Authors: Hjelmstad Gregory O. , Xia Yanfang , Margolis Elyssa B. , Fields Howard L.
Published: April 2013

Activation of mu opioid receptors within the ventral tegmental area (VTA) can produce reward through the inhibition of GABAergic inputs. GABAergic neurons in the ventral pallidum (VP) provide a major input to VTA neurons. To determine the specific VTA neuronal targets of VP afferents and their sensitivity to mu opioid receptor agonists, we virally expressed channel rhodopsin (ChR2) in rat VP neurons and optogenetically activated their terminals in the VTA. Light activation of VP neuron terminals elicited GABAergic IPSCs in both dopamine (DA) and non-DA VTA neurons, and these IPSCs were inhibited by the mu opioid receptor agonist DAMGO. In addition, using a fluorescent retrograde marker to identify VTA-projecting VP neurons, we found them to be hyperpolarized by DAMGO. Both of these actions decrease GABAergic input onto VTA neurons, revealing two mechanisms by which endogenous or exogenous opioids can activate VTA neurons, including DA neurons.
Immature Doublecortin-Positive Hippocampal Neurons Are Important for Learning But Not for Remembering
Authors: Vukovic Jana , Borlikova Gilyana G. , Ruitenberg Marc J. , Robinson Gregory J. , Sullivan Robert K.P. , Walker Tara L. , Bartlett Perry F.
Published: April 2013

It is now widely accepted that hippocampal neurogenesis underpins critical cognitive functions, such as learning and memory. To assess the behavioral importance of adult-born neurons, we developed a novel knock-in mouse model that allowed us to specifically and reversibly ablate hippocampal neurons at an immature stage. In these mice, the diphtheria toxin receptor (DTR) is expressed under control of the doublecortin (DCX) promoter, which allows for specific ablation of immature DCX-expressing neurons after administration of diphtheria toxin while leaving the neural precursor pool intact. Using a spatially challenging behavioral test (a modified version of the active place avoidance test), we present direct evidence that immature DCX-expressing neurons are required for successful acquisition of spatial learning, as well as reversal learning, but are not necessary for the retrieval of stored long-term memories. Importantly, the observed learning deficits were rescued as newly generated immature neurons repopulated the granule cell layer upon termination of the toxin treatment. Repeat (or cyclic) depletion of immature neurons reinstated behavioral deficits if the mice were challenged with a novel task. Together, these findings highlight the potential of stimulating neurogenesis as a means to enhance learning.
Tumor Necrosis Factor-Alpha Is Produced by Dying Retinal Neurons and Is Required for Müller Glia Proliferation during Zebrafish Retinal Regeneration
Authors: Nelson Craig M. , Ackerman Kristin M. , O'Hayer Patrick , Bailey Travis J. , Gorsuch Ryne A. , Hyde David R.
Published: April 2013

Intense light exposure causes photoreceptor apoptosis in dark-adapted adultalbinozebrafish (Danio rerio). Subsequently, Müller glia increase expression of the Achaete-scute complex-like 1a (Ascl1a) and Signal transducer and activator of transcription 3 (Stat3) transcription factors and re-enter the cell cycle to yield undifferentiated neuronal progenitors that continue to proliferate, migrate to the outer nuclear layer, and differentiate into photoreceptors. A proteomic analysis of light-damaged retinal homogenates, which induced Müller glia proliferation when injected into an undamaged eye, revealed increased expression of tumor necrosis factor α (TNFα) signaling proteins relative to undamaged retinal homogenates. TNFα expression initially increased in apoptotic photoreceptors and later in Müller glia. Morpholino-mediated knockdown of TNFα expression before light damage diminished the expression of both Ascl1a and Stat3 in Müller glia and significantly reduced the number of proliferating Müller glia without affecting photoreceptor cell death. Knockdown of TNFα expression in the Müller glia resulted in fewer proliferating Müller glia, suggesting that Müller glial-derived TNFα recruited additional Müller glia to re-enter the cell cycle. While TNFα is required for increased Ascl1a and Stat3 expression, Ascl1a and Stat3 are both necessary for TNFα expression in Müller glia. Apoptotic inner retinal neurons, resulting from intravitreal injection of ouabain, also exhibited increased TNFα expression that was required for Müller glia proliferation. Thus, TNFα is the first molecule identified that is produced by dying retinal neurons and is necessary to induce Müller glia to proliferate in the zebrafish retinal regeneration response.
CaMKII-Dependent Phosphorylation of the GTPase Rem2 Is Required to Restrict Dendritic Complexity
Authors: Ghiretti Amy E. , Kenny Katelyn , Marr Michael T. , Paradis Suzanne
Published: April 2013

The morphogenesis of the dendritic arbor is a critical aspect of neuronal development, ensuring that proper neural networks are formed. However, the molecular mechanisms that underlie this dendritic remodeling remain obscure. We previously established the activity-regulated GTPase Rem2 as a negative regulator of dendritic complexity. In this study, we identify a signaling pathway whereby Rem2 regulates dendritic arborization through interactions with Ca2+/calmodulin-dependent kinases (CaMKs) in rat hippocampal neurons. Specifically, we demonstrate that Rem2 functions downstream of CaMKII but upstream of CaMKIV in a pathway that restricts dendritic complexity. Furthermore, we show that Rem2 is a novel substrate of CaMKII and that phosphorylation of Rem2 by CaMKII regulates Rem2 function and subcellular localization. Overall, our results describe a unique signal transduction network through which Rem2 and CaMKs function to restrict dendritic complexity.
Hierarchical Organization of Parietofrontal Circuits during Goal-Directed Action
Authors: Verhagen Lennart , Dijkerman H. Chris , Medendorp W. Pieter , Toni Ivan
Published: April 2013

Two parietofrontal networks share the control of goal-directed movements: a dorsomedial circuit that includes the superior parieto-occipital sulcus (sPOS) and a dorsolateral circuit comprising the anterior intraparietal sulcus (aIPS). These circuits are thought to independently control either reach and grip components (a functional dissociation), or planning and execution phases of grasping movements (a temporal dissociation). However, recent evidence of functional and temporal overlap between these circuits has undermined those models.

Here, we test an alternative model that subsumes previous accounts: the dorsolateral and dorsomedial circuits operate at different hierarchical levels, resulting in functional and temporal dependencies between their computations. We asked human participants to grasp a visually presented object, manipulating movement complexity by varying object slant. We used concurrent single-pulse transcranial magnetic stimulation and electroencephalography (TMS-EEG) to probe and record neurophysiological activity in the two circuits. Changes in alpha-band oscillations (8–12 Hz) characterized the effects of task manipulations and TMS interferences over aIPS and sPOS.

Increasing the complexity of the grasping movement was accompanied by alpha-suppression over dorsomedial parietofrontal regions, including sPOS, during both planning and execution stages. TMS interference over either aIPS or sPOS disrupted this index of dorsomedial computations; early when aIPS was perturbed, later when sPOS was perturbed, indicating that the dorsomedial circuit is temporally dependent on aIPS. TMS over sPOS enhanced alpha-suppression in inferior parietal cortex, indicating that the dorsolateral circuit can compensate for a transient sPOS perturbation. These findings suggest that both circuits specify the same grasping parameters, with dorsomedial computations depending on dorsolateral contributions.
Functional Disconnection of the Orbitofrontal Cortex and Basolateral Amygdala Impairs Acquisition of a Rat Gambling Task and Disrupts Animals' Ability to Alter Decision-Making Behavior after Reinforcer Devaluation
Authors: Zeeb Fiona D. , Winstanley Catharine A.
Published: April 2013

An inability to adjust choice preferences in response to changes in reward value may underlie key symptoms of many psychiatric disorders, including chemical and behavioral addictions. We developed the rat gambling task (rGT) to investigate the neurobiology underlying complex decision-making processes. As in the Iowa Gambling task, the optimal strategy is to avoid choosing larger, riskier rewards and to instead favor options associated with smaller rewards but less loss and, ultimately, greater long-term gain. Given the demonstrated importance of the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) in acquisition of the rGT and Iowa Gambling task, we used a contralateral disconnection lesion procedure to assess whether functional connectivity between these regions is necessary for optimal decision-making. Disrupting the OFC-BLA pathway retarded acquisition of the rGT. Devaluing the reinforcer by inducing sensory-specific satiety altered decision-making in control groups. In contrast, disconnected rats did not update their choice preference following reward devaluation, either when the devalued reward was still delivered or when animals needed to rely on stored representations of reward value (i.e., during extinction). However, all rats exhibited decreased premature responding and slower response latencies after satiety manipulations. Hence, disconnecting the OFC and BLA did not affect general behavioral changes caused by reduced motivation, but instead prevented alterations in the value of a specific reward from contributing appropriately to cost-benefit decision-making. These results highlight the role of the OFC-BLA pathway in the decision-making process and suggest that communication between these areas is vital for the appropriate assessment of reward value to influence choice.
Physiologically Inspired Model for the Visual Recognition of Transitive Hand Actions
Authors: Fleischer Falk , Caggiano Vittorio , Thier Peter , Giese Martin A.
Published: April 2013

The visual recognition of actions is an important visual function that is critical for motor learning and social communication. Action-selective neurons have been found in different cortical regions, including the superior temporal sulcus, parietal and premotor cortex. Among those are mirror neurons, which link visual and motor representations of body movements. While numerous theoretical models for the mirror neuron system have been proposed, the computational basis of the visual processing of goal-directed actions remains largely unclear. While most existing models focus on the possible role of motor representations in action recognition, we propose a model showing that many critical properties of action-selective visual neurons can be accounted for by well-established visual mechanisms. Our model accomplishes the recognition of hand actions from real video stimuli, exploiting exclusively mechanisms that can be implemented in a biologically plausible way by cortical neurons. We show that the model provides a unifying quantitatively consistent account of a variety of electrophysiological results from action-selective visual neurons. In addition, it makes a number of predictions, some of which could be confirmed in recent electrophysiological experiments.
Cortical Cholinergic Input Is Required for Normal Auditory Perception and Experience-Dependent Plasticity in Adult Ferrets
Authors: Leach Nicholas D. , Nodal Fernando R. , Cordery Patricia M. , King Andrew J. , Bajo Victoria M.
Published: April 2013

The nucleus basalis (NB) in the basal forebrain provides most of the cholinergic input to the neocortex and has been implicated in a variety of cognitive functions related to the processing of sensory stimuli. However, the role that cortical acetylcholine release plays in perception remains unclear. Here we show that selective loss of cholinergic NB neurons that project to the cortex reduces the accuracy with which ferrets localize brief sounds and prevents them from adaptively reweighting auditory localization cues in response to chronic occlusion of one ear. Cholinergic input to the cortex was disrupted by making bilateral injections of the immunotoxin ME20.4-SAP into the NB. This produced a substantial loss of both p75 neurotrophin receptor (p75NTR)-positive and choline acetyltransferase-positive cells in this region and of acetylcholinesterase-positive fibers throughout the auditory cortex. These animals were significantly impaired in their ability to localize short broadband sounds (40–500 ms in duration) in the horizontal plane, with larger cholinergic cell lesions producing greater performance impairments. Although they localized longer sounds with normal accuracy, their response times were significantly longer than controls. Ferrets with cholinergic forebrain lesions were also less able to relearn to localize sound after plugging one ear. In contrast to controls, they exhibited little recovery of localization performance after behavioral training. Together, these results show that cortical cholinergic inputs contribute to the perception of sound source location under normal hearing conditions and play a critical role in allowing the auditory system to adapt to changes in the spatial cues available.
Phosphorylation of Cofilin Regulates Extinction of Conditioned Aversive Memory via AMPAR Trafficking
Authors: Wang Yue , Dong Qing , Xu Xu-Feng , Feng Xuan , Xin Jian , Wang Dong-Dong , Yu Hui , Tian Tian , Chen Zhe-Yu
Published: April 2013

Actin dynamics provide an important mechanism for the modification of synaptic plasticity, which is regulated by the actin depolymerizing factor (ADF)/cofilin. However, the role of cofilin regulated actin dynamics in memory extinction process is still unclear. Here, we observed that extinction of conditioned taste aversive (CTA) memory led to temporally enhanced ADF/cofilin activity in the infralimbic cortex (IrL) of the rats. Moreover, temporally elevating ADF/cofilin activity in the IrL could accelerate CTA memory extinction by facilitating AMPAR synaptic surface recruitment, whereas inhibition of ADF/cofilin activity abolished AMPAR synaptic surface trafficking and impaired memory extinction. Finally, we observed that ADF/cofilin-regulated synaptic plasticity was not directly coupled to morphological changes of postsynaptic spines. These findings may help us understand the role of ADF/cofilin-regulated actin dynamics in memory extinction and suggest that appropriate manipulating ADF/cofilin activity might be a suitable way for therapeutic treatment of memory disorders.