bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unique Biological Activity of Botulinum D/C Mosaic Neurotoxin in Murine Species
Authors: Nakamura Keiji , Kohda Tomoko , Shibata Yuto , Tsukamoto Kentaro , Arimitsu Hideyuki , Hayashi Mitsunori , Mukamoto Masafumi , Sasakawa Nobuyuki , Kozaki Shunji 
Published: June 2012

ABSTRACT

Clostridium botulinum
types C and D cause animal botulism by the production of serotype-specific or mosaic botulinum neurotoxin (BoNT). The D/C mosaic BoNT (BoNT/DC), which is produced by the isolate from bovine botulism in Japan, exhibits the highest toxicity to mice among all BoNTs. In contrast, rats appeared to be very resistant to BoNT/DC in type C and D BoNTs and their mosaic BoNTs. We attempted to characterize the enzymatic and receptor-binding activities of BoNT/DC by comparison with those of type C and D BoNTs (BoNT/C and BoNT/D). BoNT/DC and D showed similar toxic effects on cerebellar granule cells (CGCs) derived from the mouse, but the former showed less toxicity to rat CGCs. In recombinant murine-derived vesicle-associated membrane protein (VAMP), the enzymatic activities of both BoNTs to rat isoform 1 VAMP (VAMP1) were lower than those to the other VAMP homologues. We then examined the physiological significance of gangliosides as the binding components for types C and D, and mosaic BoNTs. BoNT/DC and C were found to cleave an intracellular substrate of PC12 cells upon the exogenous addition of GM1a and GT1b gangliosides, respectively, suggesting that each BoNT recognizes a different ganglioside moiety. The effect of BoNT/DC on glutamate release from CGCs was prevented by cholera toxin B-subunit (CTB) but not by a site-directed mutant of CTB that did not bind to GM1a. Bovine adrenal chromaffin cells appeared to be more sensitive to BoNT/DC than to BoNT/C and D. These results suggest that a unique mechanism of receptor binding of BoNT/DC may differentially regulate its biological activities in animals.
Staphylococcal Superantigen-Like Protein 3 Binds to the Toll-Like Receptor 2 Extracellular Domain and Inhibits Cytokine Production Induced by Staphylococcus aureus, Cell Wall Component, or Lipopeptides in Murine Macrophages
Authors: Yokoyama Ryosuke , Itoh Saotomo , Kamoshida Go , Takii Takemasa , Fujii Satoshi , Tsuji Tsutomu , Onozaki Kikuo 
Published: June 2012

ABSTRACTStaphylococcal superantigen-like proteins (SSLs) are a family of exoproteins sharing structural similarity with superantigens, but no superantigenic activity. Corresponding host target proteins or receptors against a portion of SSLs in the family have been identified. In this study, we show that SSL3 specifically binds to Toll-like receptor 2 (TLR2) and inhibits the stimulation of macrophages by TLR2 ligands. An approximately 100-kDa protein was recovered by using recombinant His-tagged SSL3-conjugated Sepharose from the lysate of porcine spleen, and the protein was identified as porcine TLR2 by peptide mass fingerprinting analysis. The SSL3-conjugated Sepharose recovered human and mouse TLR2 but not TLR4 from human neutrophils and mouse macrophage RAW 264.7 cells, as well as a recombinant TLR2 extracellular domain chimera protein. The production levels of interleukin 12 (IL-12) from mouse macrophages treated with heat-killedStaphylococcus aureusand of tumor necrosis factor alpha (TNF-α) from RAW 264.7 cells induced by peptidoglycan or lipopeptide TLR2 ligands were strongly suppressed in the presence of SSL3. The mutation of consensus sialic acid-containing glycan-binding residues in SSL3 did not abrogate the binding ability to TLR2 or inhibitory activity on TLR2, indicating that the interaction of SSL3 with TLR2 was independent of the sialic acid-containing glycan-binding residues. These findings demonstrate that SSL3 is able to bind the extracellular domain of TLR2 and interfere with TLR2 function. The present study provides a novel mechanism of SSL3 in immune evasion ofS. aureusvia interfering with its recognition by innate immune cells.
Alveolar Macrophages in Neonatal Mice Are Inherently Unresponsive to Pneumocystis murina Infection
Authors: Kurkjian Cathryn , Hollifield Melissa , Lines J. Louise , Rogosky Amy , Empey Kerry M. , Qureshi Mahboob , Brown Stephen A. , Garvy Beth A. 
Published: June 2012

ABSTRACTPneumocystispneumonia was first diagnosed in malnourished children and has more recently been found in children with upper respiratory symptoms. We previously reported that there is a significant delay in the immune response in newborn mice infected withPneumocystiscompared to adults (Garvy BA, Harmsen AG, Infect. Immun. 64:3987–3992, 1996, and Garvy BA, Qureshi M, J. Immunol. 165:6480–6486, 2000). This delay is characterized by the failure of neonatal lungs to upregulate proinflammatory cytokines and attract T cells into the alveoli. Here, we report that regardless of the age at which we infected the mice, they failed to mount an inflammatory response in the alveolar spaces until they were 21 days of age or older. Anti-inflammatory cytokines had some role in dampening inflammation, since interleukin-10 (IL-10)-deficient pups clearedPneumocystisfaster than wild-type pups and the neutralization of transforming growth factor beta (TGF-β) with specific antibody enhanced T cell migration into the lungs at later time points. However, the clearance kinetics were similar to those of control pups, suggesting that there is an intrinsic deficiency in the ability of innate immunity to controlPneumocystis. We found, using an adoptive transfer strategy, that the lung environment contributes to association ofPneumocystisorganisms with alveolar macrophages, implying no intrinsic deficiency in the binding ofPneumocystisby neonatal macrophages. Using bothin vivoandin vitroassays, we found thatPneumocystisorganisms were less able to stimulate translocation of NF-κB to the nucleus of alveolar macrophages from neonatal mice. These data indicate that there is an early unresponsiveness of neonatal alveolar macrophages toPneumocystisinfection that is both intrinsic and related to the immunosuppressive environment found in neonatal lungs.
Symbiotic Frankia bacteria in Alnus forests in Mexico and the United States of America: is geographic location a good predictor of assemblage structure?
Authors: Higgins Logan Massie , Kennedy Peter Gault 
Published: June 2012

While the biogeography of Alnus species is well characterized, that of their microbial symbionts remains less well understood. Little is known, for example, about how the genotypic richness of Alnus-associated Frankia bacteria varies at the continental scale, and the richness of Alnus-associated Frankia at tropical latitudes has yet to be explored. In this study, we conducted sequence-based analyses of the nifH gene comparing Frankia found in root nodules of two Alnus species in central Mexico with those associated with two Alnus species in the northwestern United States of America (USA). Similar to Frankia assemblages in northwestern USA and other geographic locations, genotypic richness within the Mexican samples was low, with five genotypes total using a ≥97% nifH sequence similarity cutoff. The vast majority of Mexican sequences belonged to genotypes also very common in northwestern USA Alnus forests, although two novel Mexican genotypes were identified. Phylogenetic analyses confirmed that all of the genotypes present in Mexico belong to larger clades of Alnus-associated Frankia. Genotype- and distance-based community analyses indicated that neither geographic location nor the phylogenetic relationships among hosts are strong predictors of Frankia assemblage structure. Our results suggest that factors other than classic biogeography are more influential in determining the continental-scale distribution and diversity of Alnus-associated Frankia.
Hypholoma lateritiumisolated from coarse woody debris, the forest floor, and mineral soil in a deciduous forest in New Hampshire
Authors: Thompson Therese A. , Thorn R. Greg , Smith Kevin T. 
Published: June 2012

Fungi in the Agaricomycetes (Basidiomycota) are the primary decomposers in temperate forests of dead wood on and in the forest soil. Through the use of isolation techniques selective for saprotrophic Agaricomycetes, a variety of wood decay fungi were isolated from a northern hardwood stand in the Bartlett Experimental Forest, New Hampshire, USA. In particular, Hypholoma lateritium (Schaeff.: Fr.) P. Kumm. was isolated from basidiocarps, decaying Acer rubrum L. logs, the Oe organic soil horizon, and the E and BC mineral soil horizons. Identification was confirmed by sequence analysis of the internal transcribed spacer region of nuclear ribosomal DNA. All isolates had identical sequences in this region to previously published sequences for the species; some were monokaryotic and simple-septate and others were dikaryotic, with clamp connections. Isolates were further characterized by banding patterns (DNA fingerprints) produced with PCR primers based in simple repetitive sequences and the minisatellite M13. Nine dikaryotic isolates from basidiocarps and from soil horizons Oe, E, and BC had identical fingerprint patterns with all primers tested. The confirmed presence of H. lateritium suggests that this fungus could form a mycelial translocation network that bridges mineral and organic soil horizons and decaying logs.
Boreal forests of eastern Canada revisited: old growth, nonfire disturbances, forest succession, and biodiversity
Authors: Bergeron Yves , Fenton Nicole J. 
Published: June 2012

Boreal forests have commonly been described as dominated by monospecific postfire stands that are reburnt well before other ecological process than those occurring immediately after fire can take place. Research undertaken over the last 30 years has given us a very different perspective of the complexity of Canadian boreal forests. Old-growth forests are common and their development is controlled by nonfire disturbances. Consequently, monospecific even-aged stands can develop towards more diversified uneven-aged stands with increasing time since fire. This complex disturbance regime, including both fire and nonfire disturbances, is partially responsible for a higher than expected biodiversity (e.g., understory) in these forests. The dominating forest management model in Canadian boreal forests, based on clear-cut harvesting and regeneration of short rotation even-aged stands, does not reflect the complexities of the disturbance–succession cycle observed in Canadian natural boreal forests.
A Zebrafish Model to Study and Therapeutically Manipulate Hypoxia Signaling in Tumorigenesis
Authors: Santhakumar Kirankumar , Judson Emma C. , Elks Philip M. , McKee Sarah , Elworthy Stone , van Rooijen Ellen , Walmsley Sarah S. , Renshaw Stephen A. , Cross Simon S. , van Eeden Fredericus J.M. 
Published: June 2012

Abstract
Hypoxic signaling is a central modulator of cellular physiology in cancer. Core members of oxygen-sensing pathway including the von Hippel-Lindau tumor suppressor protein (pVHL) and the hypoxia inducible factor (HIF) transcription factors have been intensively studied, but improved organismal models might speed advances for both pathobiologic understanding and therapeutic modulation. To study HIF signaling during tumorigenesis and development in zebrafish, we developed a unique in vivo reporter for hypoxia, expressing EGFP driven by prolyl hydroxylase 3 (phd3) promoter/regulatory elements. Modulation of HIF pathway in Tg(phd3::EGFP) embryos showed a specific role for hypoxic signaling in the transgene activation. Zebrafish vhl mutants display a systemic hypoxia response, reflected by strong and ubiquitous transgene expression. In contrast to human VHL patients, heterozygous Vhl mice and vhl zebrafish are not predisposed to cancer. However, upon exposure to dimethylbenzanthracene (DMBA), the vhl heterozygous fish showed an increase in the occurrence of hepatic and intestinal tumors, a subset of which exhibited strong transgene expression, suggesting loss of Vhl function in these tumor cells. Compared with control fish, DMBA-treated vhl heterozygous fish also showed an increase in proliferating cell nuclear antigen-positive renal tubules. Taken together, our findings establish Vhl as a genuine tumor suppressor in zebrafish and offer this model as a tool to noninvasively study VHL and HIF signaling during tumorigenesis and development. Cancer Res; 72(16); 4017–27. ©2012 AACR.
Dysfunction of Nucleus Accumbens-1 Activates Cellular Senescence and Inhibits Tumor Cell Proliferation and Oncogenesis
Authors: Zhang Yi , Cheng Yan , Ren Xingcong , Hori Tsukasa , Huber-Keener Kathryn J. , Zhang Li , Yap Kai Lee , Liu David , Shantz Lisa , Qin Zheng-Hong , Zhang Suping , Wang Jianrong , Wang Hong-Gang , Shih Ie-Ming , Yang Jin-Ming 
Published: June 2012

Abstract
Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/POZ gene family, has emerging roles in cancer. We report here that NAC1 acts as a negative regulator of cellular senescence in transformed and nontransformed cells, and dysfunction of NAC1 induces senescence and inhibits its oncogenic potential. We show that NAC1 deficiency markedly activates senescence and inhibits proliferation in tumor cells treated with sublethal doses of γ-irradiation. In mouse embryonic fibroblasts from NAC1 knockout mice, following infection with a Ras virus, NAC1−/− cells undergo significantly more senescence and are either nontransformed or less transformed in vitro and less tumorigenic in vivo when compared with NAC1+/+ cells. Furthermore, we show that the NAC1-caused senescence blunting is mediated by ΔNp63, which exerts its effect on senescence through p21, and that NAC1 activates transcription of ΔNp63 under stressful conditions. Our results not only reveal a previously unrecognized function of NAC1, the molecular pathway involved and its impact on pathogenesis of tumor initiation and development, but also identify a novel senescence regulator that may be exploited as a potential target for cancer prevention and treatment. Cancer Res; 72(16); 4262–75. ©2012 AACR.
PRAK Suppresses Oncogenic ras-Induced Hematopoietic Cancer Development by Antagonizing the JNK Pathway
Authors: Yoshizuka Naoto , Lai Maoyi , Liao Rong , Cook Ryan , Xiao Changchun , Han Jiahuai , Sun Peiqing 
Published: June 2012

Abstract
The p38 mitogen-activated protein kinase (MAPK) pathway regulates multiple physiologic and pathologic processes, including cancer development. PRAK, a p38 substrate protein kinase, has previously been implicated in the suppression of skin carcinogenesis. In the current study, we show that PRAK deletion accelerates hematopoietic cancer development in a mouse model harboring an oncogenic ras allele, Eμ-N-RasG12D, specifically expressed in hematopoietic cells. Further investigation reveals that enhanced hematopoietic tumorigenesis by PRAK deficiency is associated with hyperactivation of the c-jun-NH2-kinase (JNK) pathway both in vivo and in primary hematopoietic cells isolated from spleens. In primary splenocytes, PRAK deficiency further enhanced oncogenic ras-induced cell proliferation and promoted ras-mediated colony formation on semisolid medium in a JNK-dependent manner. In addition, deletion of PRAK leads to abrogation of ras-induced accumulation of senescence markers. These findings indicate that PRAK suppresses hematopoietic cancer formation in this mouse model by antagonizing oncogenic ras-induced activation of the JNK pathway. Our results suggest that PRAK may function as a tumor suppressor in multiple types of cancers. Mol Cancer Res; 10(6); 810–20. ©2012 AACR.
Comparison of Late Potentials for 24 Hours Between Brugada Syndrome and Arrhythmogenic Right Ventricular Cardiomyopathy Using a Novel Signal-Averaging System Based on Holter ECG
Authors: Abe Atsuko , Kobayashi Kenzaburo , Yuzawa Hitomi , Sato Hideyuki , Fukunaga Shunji , Fujino Tadashi , Okano Yoshifumi , Yamazaki Junichi , Miwa Yosuke , Yoshino Hideaki , Ikeda Takanori 
Published: June 2012

Background—
Late potentials (LP) detected with signal-averaged ECGs are known to be useful in identifying patients at risk of Brugada syndrome (BS) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Because the pathophysiology is clearly different between these disorders, we clarified the LP characteristics of these disorders.

Methods and Results—

This study included 15 BS and 12 ARVC patients and 20 healthy controls. All BS patients had characteristic ECG changes and symptomatic episodes. All ARVC patients had findings that were consistent with recent criteria. Three LP parameters (filtered QRS duration, root mean square voltage of the terminal 40 ms of the filtered QRS complex, and duration of low-amplitude signals [<40 µV] in the terminal, filtered QRS complex) were continuously measured for 24 hours using a novel Holter-based signal-averaged ECG system. The incidences of LP determination in BS (80%) and ARVC (91%) patients were higher than in healthy controls (5%;
P
<0.0001 in both) but did not differ between BS and ARVC patients. In BS patients, the dynamic changes of all LP parameters were observed, and they were pronounced at nighttime. On the contrary, these findings were not observed in ARVC patients. When the SD values of the 3 LP parameters (filtered QRS duration, root mean square voltage of the terminal 40 ms of the filtered QRS complex, and duration of low-amplitude signals [<40 µV] in the terminal, filtered QRS complex) over 24 hours were compared for the 2 patient groups, those values in BS patients were significantly greater than those in ARVC patients (
P
<0.0001 in all).

Conclusions—
LP characteristics detected by the Holter-based signal-averaged ECG system over 24 hours differ between BS and ARVC patients. Dynamic daily variations of LPs were seen only in BS patients. This may imply that mechanisms of lethal ventricular arrhythmia in BS may be more correlated with autonomic abnormality than that of ARVC.
Early Results of Fenestrated Endovascular Repair of Juxtarenal Aortic Aneurysms in the United Kingdom
Authors: Ambler G. , Boyle J.R. , Cousins C. , Hayes P.D. , Metha T. , See T.C. , Varty K. , Winterbottom A. , Adam D.J. , Bradbury A.W. , Clarke M.J. , Jackson R. , Rose J.D. , Sharif A. , Wealleans V. , Williams R. , Wilson L. , Wyatt M.G. , Ahmed I. , Bell R.E. , Carrell T.W. , Gkoutzios P. , Sabharwal T. , Salter R. , Waltham M. , Bicknell C. , Bourke P. , Cheshire N. , Franklin I. , James A. , Jenkins M.P. , Tyrrell M.R. , Wilkins C.J. , Bown M. , Choke E. , McCarthy M. , Sayers R. , Tamberaja A. , Farquharson F. , Serracino-Inglott F. , Davis M. , Hamilton G. , Brennan J.A. , Canavati R. , Fisher R.K. , McWilliams R.G. , Naik J.B. , Vallabhaneni S.R. , Hardman J. , Black S. , Hinchliffe R. , Holt P. , Loftus I.M. , Loosemore T. , Morgan R , Thompson M.M. , Agu O. , Bishop C. , Boardley D. , Cross J. , Hague J. , Harris P.L. , Ivancev K. , Raja J. , Richards T. , Simring D. , Fisher A.C. , Smith D. , Copeland G.P. 
Published: June 2012

Background—
Fenestrated endovascular repair of abdominal aortic aneurysms has been proposed as an alternative to open surgery for juxtarenal and pararenal abdominal aortic aneurysms. At present, the evidence base for this procedure is predominantly limited to single-center or single-operator series. The aim of this study was to present nationwide early results of fenestrated endovascular repair in the United Kingdom.

Methods and Results—
All patients who underwent fenestrated endovascular repair between January 2007 and December 2010 at experienced institutions in the United Kingdom(>10 procedures) were retrospectively studied by use of the GLOBALSTAR database. Site-reported data relating to patient demographics, aneurysm morphology, procedural details, and outcome were recorded. Data from 318 patients were obtained from 14 centers. Primary procedural success was achieved in 99% (316/318); perioperative mortality was 4.1%, and intraoperative target vessel loss was observed in 5 of 889 target vessels (0.6%). The early reintervention (<30 days) rate was 7% (22/318). There were 11 deaths during follow-up; none were aneurysm-related. Survival by Kaplan–Meier analysis was 94% (SE 0.01), 91% (0.02), and 89% (0.02) at 1, 2, and 3 years, respectively. Freedom from target vessel loss was 93% (0.02), 91% (0.02), and 85% (0.06), and freedom from late secondary intervention (>30 days) was 90% (0.02), 86% (0.03), and 70% (0.08) at 1, 2, and 3 years.

Conclusions—
In this national sample, fenestrated endovascular repair has been performed with a high degree of technical and clinical success. Late survival and target vessel patency are satisfactory. These results support continued use and evaluation of this technique for juxtarenal aneurysms, but illustrate the need for a more robust evidence base.
Transient Tropospheric Forcing of Sudden Stratospheric Warmings
Authors: Sjoberg Jeremiah P. , Birner Thomas 
Published: June 2012

Abstract
The amplitude of upward-propagating tropospherically forced planetary waves is known to be of first-order importance in producing sudden stratospheric warmings (SSWs). This forcing amplitude is observed to undergo strong temporal fluctuations. Characteristics of the resulting transient forcing leading to SSWs are studied in reanalysis data and in highly truncated simple models of stratospheric wave–mean flow interaction. It is found in both the reanalysis data and the simple models that SSWs are preferentially generated by transient forcing of sufficiently long time scales (on the order of 1 week or longer). The time scale of the transient forcing is found to play a stronger role in producing SSWs than the strength of the forcing. In the simple models it is possible to fix the amplitude of the tropospheric forcing but to vary the time scale of the forcing. The resulting frequency of occurrence of SSWs shows dramatic reductions for decreasing forcing time scales.
Finite-Amplitude Lagrangian-Mean Wave Activity Diagnostics Applied to the Baroclinic Eddy Life Cycle
Authors: Solomon Abraham , Chen Gang , Lu Jian 
Published: June 2012

Abstract
Lagrangian-mean wave activity diagnostics are applied to the nonlinear baroclinic eddy life cycle in a simple general circulation model of the atmosphere. The growth of these instabilities through baroclinic conversion of potential temperature gradients and their subsequent barotropic decay can exhibit two distinct life cycles. One life cycle results in equatorward propagation of the growing eddy, anticyclonic wave breaking, and a poleward shift of the mean jet. The second life cycle is distinguished by limited equatorward propagation and cyclonic wave breaking on the poleward flank of the jet. Using a conservative finite-amplitude, Lagrangian-mean wave activity (negative pseudomomentum) to quantify wave growth and propagation reveals more details about the life cycles than could be discerned from eddy kinetic energy (EKE) or other Eulerian metrics. It is shown that the distribution of pseudomomentum relative to the latitude of the axis of the jet can be used to provide a clear distinction between the two life cycles at an early stage in their development and, hence, a prediction for the subsequent shift of the jet. This suggests that the distribution of pseudomomentum may provide some predictability for the atmospheric annular modes.