bluuebunny/crossref_metadata_2025_split huggingface dataset:
Narasin, a Novel Antiviral Compound that Blocks Dengue Virus Protein Expression
Authors: Low June Su Yin , Wu Kan Xing , Chen Karen Caiyun , Ng Mary Mah-Lee , Chu Justin Jang Hann 
Published: August 2011

Background Dengue virus (DENV) is a mosquito-borne virus that causes a spectrum of human diseases ranging from mild dengue fever to dengue haemorrhagic fever and dengue shock syndrome in severe cases. Currently, there is no effective antiviral therapy or vaccine against DENV infection. Methods In order to identify potential antiviral agents against DENV, we performed high-throughput cell-based screening on a highly purified natural products library. Among the screening hits, selected compounds which displayed 50–75% inhibition against DENV2 were validated using secondary assays. Time-of-addition studies, dose-dependent assays, real time quantitative reverse transcriptase (RT)-PCR, Western blot and ultrastructural imaging were conducted in an attempt to elucidate the potential antiviral mechanisms of narasin. Results In this study, an ionophore, narasin was selected for detailed analysis due to its strong inhibitory profile against DENV infection with minimal cytotoxicity (50% cytotoxic concentration >1,000 μM). A dose- dependent study revealed narasin to have an 50% inhibitory concentration of less than 1 μM against all four serotypes of DENV. Time-of-addition studies of narasin-treated, DENV2- infected Huh-7 cells suggested narasin to be involved in inhibiting the post-entry stages of viral replication during DENV infection. Proteomic and ultrastructural analyses revealed the antiviral mechanism of narasin as likely to be associated with the disruption of viral protein synthesis. In addition, quantitative RT-PCR studies showed no differences in viral RNA levels between narasin- treated and control DENV2-infected cells. Conclusions Narasin was identified and characterized as a novel agent that inhibits DENV replication in vitro through non-cytotoxic mechanisms, thus indicating its potential to be further developed as a therapeutic anti-DENV agent.
Treatment of Mucosa-associated Lymphoid Tissue Lymphoma in Sjögren’s Syndrome: A Retrospective Clinical Study
Authors: POLLARD RODNEY P.E. , PIJPE JUSTIN , BOOTSMA HENDRIKA , SPIJKERVET FRED K.L. , KLUIN PHILIP M. , ROODENBURG JAN L.N. , KALLENBERG CEES G.M. , VISSINK ARJAN , van IMHOFF GUSTAAF W. 
Published: August 2011

Objective.To retrospectively analyze the clinical course of patients with mucosa-associated lymphoid tissue (MALT)-type lymphoma of the parotid gland and associated Sjögren’s syndrome (SS).Methods.All consecutive patients with SS and MALT lymphoma (MALT-SS) diagnosed in the University Medical Center Groningen between January 1997 and January 2009 were analyzed. Clinical course and treatment outcome of SS and MALT lymphoma were evaluated.Results.From a total of 329 patients with SS, 35 MALT-SS patients were identified, with a median followup of 76 months (range 16–153 mo). MALT lymphoma was localized in the parotid gland in all cases. Treatment consisted of “watchful waiting” (n = 10), surgery (n = 3), radiotherapy (n = 1), surgery combined with radiotherapy (n = 2), rituximab only (n = 13), or rituximab combined with chemotherapy (n = 6). Complete response was observed in 14 patients, partial response in 1 patient, and stable disease in 20 patients. In 6 of 7 patients with initially high SS disease activity (M-protein, cryoglobulins, IgM rheumatoid factor > 100 KIU/l, severe extraglandular manifestations), MALT lymphoma progressed and/or SS disease activity increased after a median followup of 39 months (range 4–98 mo), necessitating retreatment. Only 1 patient with MALT who had low SS disease activity showed progression of lymphoma when left untreated.Conclusion.An initially high SS disease activity likely constitutes an adverse prognostic factor for progression of lymphoma and/or SS. Such patients may require treatment for both MALT lymphoma and SS. In SS patients with localized asymptomatic MALT lymphoma and low SS disease activity, a “watchful waiting” strategy seems justified.
Suppressor of Cytokine Signaling 2 Is a Feedback Inhibitor of TLR-Induced Activation in Human Monocyte-Derived Dendritic Cells
Authors: Posselt Gernot , Schwarz Harald , Duschl Albert , Horejs-Hoeck Jutta 
Published: August 2011

Abstract
Dendritic cells (DCs) are key players in initiating and directing the immune response. Therefore, their activation state and functional differentiation need to be tightly controlled. The activating stimuli and their signaling networks have long been an area of focus in DC research. Recent investigations have also shed light on the mechanisms of counterregulation and fine-tuning of DC functions. One class of proteins involved in these processes is the family of suppressors of cytokine signaling (SOCS), whose members were originally described as feedback inhibitors of cytokine-induced JAK/STAT signaling. Essential roles in DC function have been assigned to SOCS1 and SOCS3. In this article, we show that SOCS2 also is involved in DC regulation. In human and in murine DCs, SOCS2 is a highly TLR-responsive gene, which is expressed in a time-delayed fashion beginning 8 h after TLR ligation. Functionally, silencing of SOCS2 in DCs results in hyperphosphorylation of STAT3 at later time points. As a consequence, SOCS2-deficient DCs secrete increased amounts of the cytokines IL-1β and IL-10, both being transcriptional targets of STAT3. We propose a model in which SOCS2 acts as a negative regulator of TLR-induced DC activation. The delayed expression of SOCS2 provides a mechanism of late-phase counterregulation and limitation of inflammation-driving DC activity.
Differential Regulation of Proximal and Distal Vβ Segments Upstream of a Functional VDJβ1 Rearrangement upon β-Selection
Authors: Brady Brenna L. , Bassing Craig H. 
Published: August 2011

Abstract
Developmental stage-specific regulation of transcriptional accessibility helps control V(D)J recombination. Vβ segments on unrearranged TCRβ alleles are accessible in CD4−/CD8− (double-negative [DN]) thymocytes, when they recombine, and inaccessible in CD4+/CD8+ (double-positive [DP]) thymocytes, when they do not rearrange. Downregulation of Vβ accessibility on unrearranged alleles is linked with Lat-dependent β-selection signals that inhibit Vβ rearrangement, stimulate Ccnd3-driven proliferation, and promote DN-to-DP differentiation. Transcription and recombination of Vβs on VDJβ-rearranged alleles in DN cells has not been studied; Vβs upstream of functional VDJβ rearrangements have been found to remain accessible, yet not recombine, in DP cells. To elucidate contributions of β-selection signals in regulating Vβ transcription and recombination on VDJβ-rearranged alleles, we analyzed wild-type, Ccnd3−/−, and Lat−/− mice containing a preassembled functional Vβ1DJCβ1 (Vβ1NT) gene. Vβ10 segments located just upstream of this VDJCβ1 gene were the predominant germline Vβs that rearranged in Vβ1NT/NT and Vβ1NT/NTCcnd3−/− thymocytes, whereas Vβ4 and Vβ16 segments located further upstream rearranged at similar levels as Vβ10 in Vβ1NT/NTLat−/− DN cells. We previously showed that Vβ4 and Vβ16, but not Vβ10, are transcribed on Vβ1NT alleles in DP thymocytes; we now demonstrate that Vβ4, Vβ16, and Vβ10 are transcribed at similar levels in Vβ1NT/NTLat−/− DN cells. These observations indicate that suppression of Vβ rearrangements is not dependent on Ccnd3-driven proliferation, and DN residence can influence the repertoire of Vβs that recombine on alleles containing an assembled VDJCβ1 gene. Our findings also reveal that β-selection can differentially silence rearrangement of germline Vβ segments located proximal and distal to functional VDJβ genes.
EBI2 Guides Serial Movements of Activated B Cells and Ligand Activity Is Detectable in Lymphoid and Nonlymphoid Tissues
Authors: Kelly Lisa M. , Pereira João P. , Yi Tangsheng , Xu Ying , Cyster Jason G. 
Published: August 2011

Abstract
EBV-induced gene 2 (EBI2) was recently shown to direct the delayed movement of activated B cells to interfollicular and outer follicular regions of secondary lymphoid organs and to be required for mounting a normal T-dependent Ab response. In this study, we show that EBI2 promotes an early wave of Ag-activated B cell migration to the outer follicle in mice. Later, when B cells have moved to the T zone in a CCR7-dependent manner, EBI2 helps distribute the cells along the B zone–T zone boundary. Subsequent EBI2-dependent movement to the outer follicle coincides with CCR7 downregulation and is promoted by CD40 engagement. Using a bioassay, we identify a proteinase K-resistant, hydrophobic EBI2 ligand activity in lymphoid and nonlymphoid tissues. Production of EBI2 ligand activity by a cell line is sensitive to statins, suggesting production in a 3-hydroxy-3-methyl-glutaryl-CoA reductase–dependent manner. CD40-activated B cells show sustained EBI2-dependent responsiveness to the bioactivity. These findings establish a role for EBI2 in helping control B cell position at multiple stages during the Ab response and they suggest that EBI2 responds to a broadly distributed lipid ligand.
Novel Highly Sensitive IL-10–β-Lactamase Reporter Mouse Reveals Cells of the Innate Immune System as a Substantial Source of IL-10 In Vivo
Authors: Bouabe Hicham , Liu Yunying , Moser Markus , Bösl Michael R. , Heesemann Jürgen 
Published: August 2011

Abstract
In this study, we report on a novel, highly sensitive IL-10 reporter mouse based on the reporter enzyme β-lactamase and the fluorescence resonance energy transfer substrate coumarin-cephalosporin-fluorescein (4). In contrast to an IL-10 reporter mouse model that we generated by using enhanced GFP as reporter and allowed tracking IL-10 expression only in T cells, the IL-10–β-lactamase reporter (ITIB) mouse enables us to easily analyze and quantify IL-10 production at the single-cell level in all myeloid and lymphoid cell types. Furthermore, the ITIB mouse allows studying of the kinetics of IL-10 expression on a single-cell basis and provides a valuable tool for in vivo screening of cell type-specific IL-10–modulating drugs. Remarkably, the ITIB mouse revealed that, although a significant portion of each myeloid and lymphoid cell type produces IL-10, macrophages represent the major IL-10 producer population in several organs of naive mice. Moreover, using the examples of bacterial infection and transplantable skin melanoma models, we demonstrate the exceptional applicability of the ITIB mouse for the identification of IL-10–producing cells during immune responses in vivo. In this study, we identified tumor-infiltrating F4/80+ macrophages as the major source for IL-10 in B16-F10 melanoma in vivo. During systemic infection with Yersinia enterocolitica, although the proportion of IL-10+ cells increased in each myeloid and lymphoid cell type population, infiltrating CD11b+Ly6G+ neutrophils represent a majority among IL-10–producing cells at the site of infection. We conclude that cells of the innate immune system that are involved in immune homeostasis or immune responses are substantial sources of IL-10.
Guanidine Alkaloids from Monanchora arbuscula: Chemistry and Antitumor Potential
Authors: Ferreira Elthon G. , Wilke Diego V. , Jimenez Paula C. , de Oliveira Julieta R. , Pessoa Otília Deusdênia L. , Silveira Edilberto R. , Viana Francisco A. , Pessoa Cláudia , de Moraes Manoel Odorico , Hajdu Eduardo , Costa‐Lotufo Letícia Veras 
Published: August 2011

AbstractFive guanidine alkaloids, mirabilin B (1), 8bβ‐hydroxyptilocaulin (2), ptilocaulin (3), and a mixture of the 8β‐ and 8α‐epimers, 4 and 5, of 8‐hydroxymirabilin (1,8a;8b,3a‐didehydro‐8‐hydroxyptilocaulin), were isolated from Monanchora arbuscula colonies collected off the northeastern Brazilian coast. All structures were elucidated by spectroscopic analysis, including 1D (1H‐, 13C‐ (BB), and 13C‐DEPT) and 2D (COSY, HSQC, and HMBC) NMR experiments, and comparison with the literature data. The cytotoxicity of the isolated compounds were evaluated against four tumor cell lines, showing that mirabilin B (1) and the two epimers were inactive, while 8bβ‐hydroxyptilocaulin (2) and ptilocaulin (3) presented IC50 values in the range of 7.9 to 61.5 μM, and 5.8 to 40.0 μM, respectively. Further studies on the mechanism of action of ptilocaulin, using HL‐60 leukemia cells, demonstrated that this guanidine compound induced apoptosis of the treated cells.
A conformal transceive array for 7 T neuroimaging
Authors: Gilbert Kyle M. , Belliveau Jean‐Guy , Curtis Andrew T. , Gati Joseph S. , Klassen L. Martyn , Menon Ravi S. 
Published: August 2011

AbstractThe first 16‐channel transceive surface‐coil array that conforms to the human head and operates at 298 MHz (7 T) is described. Individual coil elements were decoupled using circumferential shields around each element that extended orthogonally from the former. This decoupling method allowed elements to be constructed with arbitrary shape, size, and location to create a three‐dimensional array. Radiofrequency shimming achieved a transmit‐field uniformity of 20% over the whole brain and 14% over a single axial slice. During radiofrequency transmission, coil elements couple tightly to the head and reduce the amount of power necessary to achieve a mean 90° flip angle (660‐μs and 480‐μs pulse lengths were required for a 1‐kW hard pulse when shimming over the whole brain and a single axial slice, respectively). During reception, the close proximity of coil elements to the head increases the signal‐to‐noise ratio in the periphery of the brain, most notably at the superior aspect of the head. The sensitivity profile of each element is localized beneath the respective shield. When combined with the achieved isolation between elements, this results in the capacity for low geometry factors during both transmit and receive: 1.04/1.06 (mean) and 1.25/1.54 (maximum) for 3‐by‐3 acceleration in the axial/sagittal plane. High cortical signal‐to‐noise ratio and parallel imaging performance make the conformal coil ideal for the study of high temporal and/or spatial cortical architecture and function. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Failure of propranolol in the treatment of childhood haemangiomas of the head and neck
Authors: Goswamy J , Rothera M P , Bruce I A 
Published: August 2011

AbstractBackground:Infantile haemangiomas enter a rapid proliferative phase within months of birth, before slowly involuting. Those with the potential for disfigurement or morbidity require intervention. Propranolol has emerged as an effective new treatment modality, with the potential to become the first-line treatment of choice.Methods:Four children with haemangiomas of the head and neck were treated with propranolol at a tertiary referral centre. The size of the haemangioma and the symptoms resulting from airway compromise were monitored.Results:Three of the four children showed a dramatic response to treatment with propranolol. However, one child responded initially but was readmitted with stridor secondary to new haemangioma proliferation.Conclusions:We report a cautionary case in which a subglottic haemangioma developed contemporaneously with propranolol treatment, requiring surgical intervention. This finding highlights the need for regular follow up of treatment response, and the need for monitoring for treatment side effects.
A new era in supraglottitis? An isolated UK case of supraglottitis secondary toNeisseria meningitidis
Authors: Sarwar U , Akhtar N , Hemming J , Dennis S 
Published: August 2011

AbstractObjective:We report the first UK case of supraglottitis secondary toNeisseria meningitidis.Method:Case report with review of the current literature on supraglottitis and its aetiology.Results:An 89-year-old woman was referred with worsening symptoms of dysphagia, hoarseness and neck discomfort. After nasopharyngoscopy and neck X-ray, supraglottitis was diagnosed. Prompt treatment comprised nebulised adrenaline, oxygen therapy and intravenous antibiotics. Microbiology samples grewN meningitidis, a notifiable disease in the UK. Public health officials were informed, and full precautions and prophylactic treatment initiated for those at risk. The patient made excellent progress and was discharged several days later.Discussion and conclusion:Supraglottitis occurs in <4 per 100 000 population. Following a successful UK childhood immunisation programme, most cases occur in adults. Supraglottitis secondary toN meningitidisis exceptionally rare, with only seven other reported cases worldwide. Morbidity is exceptionally high; over 60 per cent of patients require airway intervention. To our knowledge, this is the first reported UK case of supraglottitis secondary toN meningitidis. This case highlights the important clinical, diagnostic and therapeutic interventions required to prevent complications associated with this potentially fatal condition.
The Arabidopsis bZIP Gene AtbZIP63 Is a Sensitive Integrator of Transient Abscisic Acid and Glucose Signals
Authors: Matiolli Cleverson Carlos , Tomaz Juarez Pires , Duarte Gustavo Turqueto , Prado Fernanda Manso , Del Bem Luiz Eduardo Vieira , Silveira Amanda Bortolini , Gauer Luciane , Corrêa Luiz Gustavo Guedes , Drumond Rodrigo Duarte , Viana Américo José Carvalho , Di Mascio Paolo , Meyer Christian , Vincentz Michel 
Published: August 2011

AbstractGlucose modulates plant metabolism, growth, and development. In Arabidopsis (Arabidopsis thaliana), Hexokinase1 (HXK1) is a glucose sensor that may trigger abscisic acid (ABA) synthesis and sensitivity to mediate glucose-induced inhibition of seedling development. Here, we show that the intensity of short-term responses to glucose can vary with ABA activity. We report that the transient (2 h/4 h) repression by 2% glucose of AtbZIP63, a gene encoding a basic-leucine zipper (bZIP) transcription factor partially involved in the Snf1-related kinase KIN10-induced responses to energy limitation, is independent of HXK1 and is not mediated by changes in ABA levels. However, high-concentration (6%) glucose-mediated repression appears to be modulated by ABA, since full repression of AtbZIP63 requires a functional ABA biosynthetic pathway. Furthermore, the combination of glucose and ABA was able to trigger a synergistic repression of AtbZIP63 and its homologue AtbZIP3, revealing a shared regulatory feature consisting of the modulation of glucose sensitivity by ABA. The synergistic regulation of AtbZIP63 was not reproduced by an AtbZIP63 promoter-5′-untranslated region::β-glucuronidase fusion, thus suggesting possible posttranscriptional control. A transcriptional inhibition assay with cordycepin provided further evidence for the regulation of mRNA decay in response to glucose plus ABA. Overall, these results indicate that AtbZIP63 is an important node of the glucose-ABA interaction network. The mechanisms by which AtbZIP63 may participate in the fine-tuning of ABA-mediated abiotic stress responses according to sugar availability (i.e., energy status) are discussed.
The virtue of uncertainty in health care
Authors: Buetow Stephen 
Published: August 2011

AbstractUncertainty is unavoidable in health care, yet frequently tacit. When uncertainty is acknowledged, it tends to be defined in terms of the unpredictable nature of the care, and limits to human knowledge. It is cast as a problem that evidence‐based health care can minimize. Challenging that simplistic perspective, this paper reconstructs uncertainty as a property whose meaning derives from how people are relationally disposed to perceive it in the social context in which they are embedded. Five conditions are suggested to define a need to protect and cultivate uncertainty as a virtue or positive disposition. These conditions are that uncertainty is natural, promotes creativity and a critical attitude, can signify wisdom, nurtures safety, sustains hope and protects against excess. In contrast, certainty is a delusion. Believing in certainty is unscientific and antiscientific because it can obscure and devalue critique in scientific practice.
Physical punishment of children: Can we continue to accept the status quo?
Authors: Oates Kim 
Published: August 2011

AbstractAll children require discipline, although physical punishment is just one form of discipline. Parental use of physical punishment is inter‐generational. There is now evidence that physical punishment of children is not only less effective than other forms of discipline but can also lead to aggressive behaviour in childhood and adult life. Twenty‐nine countries, including New Zealand, have laws against physical punishment in the home. Australian attitudes are slowly changing in favour of less use of physical punishment, but there is a long way to go. As advocates for children, paediatricians should not be content to accept the status quo.
Comparison of the psychosocial quality of life in hemodialysis patients between the elderly and non‐elderly using a visual analogue scale: The importance of appetite and depressive mood
Authors: Kanamori Hiroshi , Nagai Kojiro , Matsubara Takeshi , Mima Akira , Yanagita Motoko , Iehara Noriyuki , Takechi Hajime , Fujimaki Keiichi , Usami Kazumasa , Fukatsu Atsushi , Kita Toru , Matsubayashi Kozo , Arai Hidenori 
Published: August 2011

Aim:  The number of hemodialysis (HD) patients is increasing along with their mean age in Japan. The assessment of their psychosocial status and quality of life (QOL) is therefore becoming more and more important along with laboratory data or comorbidities.Methods:  We examined the psychosocial status of 211 HD patients (72 elderly and 139 non‐elderly) and compared the difference between elderly and non‐elderly patients using a visual analogue scale (VAS). We then examined how QOL affected mortality rate in 3‐year prospective follow up. We assessed 10 items of QOL: health condition, appetite, sleep, mood, memory, family relationships, friendship, economical status, life satisfaction in daily life, and happiness with qualified self‐evaluating questionnaires along with laboratory data and comorbidities. Furthermore, we investigated the correlation between the scores of mood and geriatric depression scale (GDS)‐15.Results:  There was no difference in VAS scores between elderly and non‐elderly patients. Lower VAS scores for appetite and mood correlated with higher mortality in HD patients, especially in the non‐elderly. VAS scores for mood correlated with GDS‐15 in HD patients.Conclusions:  More attention should be paid to appetite and the diagnosis and therapy of depressive mood to improve the prognosis of HD patients, especially for the non‐elderly. Geriatr Gerontol Int 2012; 12: 65–71.
Anidulafungin in Treatment of Experimental Invasive Infection by Candida parapsilosis:
In Vitro
Activity, (1→3)-β-
d
-Glucan and Mannan Serum Levels, Histopathological Findings, and
In Vivo
Efficacy
Authors: Salas Valentina , Pastor F. Javier , Calvo Enrique , Mayayo Emilio , Quindós Guillermo , Carrillo Alfonso J. , Guarro Josep 
Published: August 2011

ABSTRACT

We have evaluated the
in vitro
activity of anidulafungin (AFG) against 31 strains of
Candida parapsilosis
sensu stricto by using broth microdilution, disk diffusion, and minimal fungicidal concentration (MFC) determination procedures. The two first methods showed a high level of activity of the drug, while MFCs were 1 to 5 dilutions higher than their corresponding MICs. To assess if MICs were predictive of
in vivo
outcomes, six strains representing different AFG MICs (0.12 to 2 μg/ml) were tested in a murine model of disseminated infection treated with different doses of the drug (1, 5, or 10 mg/kg of body weight). AFG was able to prolong the survival of mice infected with all the strains tested but was able to reduce the tissue burden of those mice infected only with the strains that showed the lowest MIC (0.12 μg/ml).