bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of PAI-1 induces neutrophil-driven neoangiogenesis and promotes tissue regeneration via production of angiocrine factors in mice
Authors: Tashiro Yoshihiko , Nishida Chiemi , Sato-Kusubata Kaori , Ohki-Koizumi Makiko , Ishihara Makoto , Sato Aki , Gritli Ismael , Komiyama Hiromitsu , Sato Yayoi , Dan Takashi , Miyata Toshio , Okumura Ko , Tomiki Yuichi , Sakamoto Kazuhiro , Nakauchi Hiromitsu , Heissig Beate , Hattori Koichi
Published: May 2012

Plasminogen activator inhibitor-1 (PAI-1), an endogenous inhibitor of a major fibrinolytic factor, tissue-type plasminogen activator, can both promote and inhibit angiogenesis. However, the physiologic role and the precise mechanisms underlying the angiogenic effects of PAI-1 remain unclear. In the present study, we report that pharmacologic inhibition of PAI-1 promoted angiogenesis and prevented tissue necrosis in a mouse model of hind-limb ischemia. Improved tissue regeneration was due to an expansion of circulating and tissue-resident granulocyte-1 marker (Gr-1+) neutrophils and to increased release of the angiogenic factor VEGF-A, the hematopoietic growth factor kit ligand, and G-CSF. Immunohistochemical analysis indicated increased amounts of fibroblast growth factor-2 (FGF-2) in ischemic gastrocnemius muscle tissues of PAI-1 inhibitor-treated animals. Ab neutralization and genetic knockout studies indicated that both the improved tissue regeneration and the increase in circulating and ischemic tissue-resident Gr-1+ neutrophils depended on the activation of tissue-type plasminogen activator and matrix metalloproteinase-9 and on VEGF-A and FGF-2. These results suggest that pharmacologic PAI-1 inhibition activates the proangiogenic FGF-2 and VEGF-A pathways, which orchestrates neutrophil-driven angiogenesis and induces cell-driven revascularization and is therefore a potential therapy for ischemic diseases.
Impact of immune modulation with in vivo T-cell depletion and myleoablative total body irradiation conditioning on outcomes after unrelated donor transplantation for childhood acute lymphoblastic leukemia
Authors: Veys Paul , Wynn Robert F. , Ahn Kwang Woo , Samarasinghe Sujith , He Wensheng , Bonney Denise , Craddock John , Cornish Jacqueline , Davies Stella M. , Dvorak Christopher C. , Duerst Reggie E. , Gross Thomas G. , Kapoor Neena , Kitko Carrie , Krance Robert A. , Leung Wing , Lewis Victor A. , Steward Colin , Wagner John E. , Carpenter Paul A. , Eapen Mary
Published: May 2012

To determine whether in vivo T-cell depletion, which lowers GVHD, abrogates the antileukemic benefits of myeloablative total body irradiation–based conditioning and unrelated donor transplantation, in the present study, we analyzed 715 children with acute lymphoblastic leukemia. Patients were grouped for analysis according to whether conditioning included antithymocyte globulin (ATG; n = 191) or alemtuzumab (n = 132) and no in vivo T-cell depletion (n = 392). The median follow-up time was 3.5 years for the ATG group and 5 years for the alemtuzumab and T cell–replete groups. Using Cox regression analysis, we compared transplantation outcomes between groups. Compared with no T-cell depletion, grade 2-4 acute and chronic GVHD rates were significantly lower after in vivo T-cell depletion with ATG (relative risk [RR] = 0.66; P = .005 and RR = 0.55; P < .0001, respectively) or alemtuzumab (RR = 0.09; P < .003 and RR = 0.21; P < .0001, respectively). Despite lower GVHD rates after in vivo T-cell depletion, nonrelapse mortality, relapse, overall survival, and leukemia-free survival (LFS) did not differ significantly among the treatment groups. The 3-year probabilities of LFS after ATG-containing, alemtuzumab-containing, and T cell–replete transplantations were 43%, 49%, and 46%, respectively. These data suggest that in vivo T-cell depletion lowers GVHD without compromising LFS among children with acute lymphoblastic leukemia who are undergoing unrelated donor transplantation with myeloablative total body irradiation–based regimens.
Improving the performance of true single molecule sequencing for ancient DNA
Authors: Ginolhac Aurelien , Vilstrup Julia , Stenderup Jesper , Rasmussen Morten , Stiller Mathias , Shapiro Beth , Zazula Grant , Froese Duane , Steinmann Kathleen E , Thompson John F , AL-Rasheid Khaled AS , Gilbert Thomas MP , Willerslev Eske , Orlando Ludovic
Published: May 2012

Background

Second-generation sequencing technologies have revolutionized our ability to recover genetic information from the past, allowing the characterization of the first complete genomes from past individuals and extinct species. Recently, third generation Helicos sequencing platforms, which perform true Single-Molecule DNA Sequencing (tSMS), have shown great potential for sequencing DNA molecules from Pleistocene fossils. Here, we aim at improving even further the performance of tSMS for ancient DNA by testing two novel tSMS template preparation methods for Pleistocene bone fossils, namely oligonucleotide spiking and treatment with DNA phosphatase.

Results

We found that a significantly larger fraction of the horse genome could be covered following oligonucleotide spiking however not reproducibly and at the cost of extra post-sequencing filtering procedures and skewed %GC content. In contrast, we showed that treating ancient DNA extracts with DNA phosphatase improved the amount of endogenous sequence information recovered per sequencing channel by up to 3.3-fold, while still providing molecular signatures of endogenous ancient DNA damage, including cytosine deamination and fragmentation by depurination. Additionally, we confirmed the existence of molecular preservation niches in large bone crystals from which DNA could be preferentially extracted.

Conclusions

We propose DNA phosphatase treatment as a mechanism to increase sequence coverage of ancient genomes when using Helicos tSMS as a sequencing platform. Together with mild denaturation temperatures that favor access to endogenous ancient templates over modern DNA contaminants, this simple preparation procedure can improve overall Helicos tSMS performance when damaged DNA templates are targeted.
RND type efflux pump system MexAB-OprM of pseudomonas aeruginosa selects bacterial languages, 3-oxo-acyl-homoserine lactones, for cell-to-cell communication
Authors: Minagawa Shu , Inami Hiroyuki , Kato Tomohisa , Sawada Shinji , Yasuki Tatsuya , Miyairi Shinichi , Horikawa Manabu , Okuda Jun , Gotoh Naomasa
Published: May 2012

Background

Bacteria release a wide variety of small molecules including cell- to- cell signaling compounds. Gram-negative bacteria use a variety of self-produced autoinducers such as acylated homoserine lactones (acyl- HSLs) as signal compounds for quorum sensing (QS) within and between bacterial species. QS plays a significant role in the pathogenesis of infectious diseases and in beneficial symbiosis by responding to acyl- HSLs in Pseudomonas aeruginosa. It is considered that the selection of bacterial languages is necessary to regulate gene expression and thus it leads to the regulation of virulence and provides a growth advantage in several environments. In this study, we hypothesized that RND-type efflux pump system MexAB- OprM of P. aeruginosa might function in the selection of acyl- HSLs, and we provide evidence to support this hypothesis.

Results

Loss of MexAB- OprM due to deletion of mexB caused increases in QS responses, as shown by the expression of gfp located downstream of the lasB promoter and LasB elastase activity, which is regulated by a LasR- 3- oxo- C12- HSL complex. Either complementation with a plasmid containing wild- type mexB or the addition of a LasR- specific inhibitor, patulin, repressed these high responses to 3- oxo- acyl- HSLs. Furthermore, it was shown that the acyl- HSLs- dependent response of P. aeruginosa was affected by the inhibition of MexB transport activity and the mexB mutant. The P. aeruginosa MexAB- OprM deletion mutant showed a strong QS response to 3- oxo- C10- HSL produced by Vibrio anguillarum in a bacterial cross- talk experiment.

Conclusion

This work demonstrated that MexAB- OprM does not control the binding of LasR to 3-oxo-Cn-HSLs but rather accessibility of non-cognate acyl-HSLs to LasR in P. aeruginosa. MexAB- OprM not only influences multidrug resistance, but also selects acyl- HSLs and regulates QS in P. aeruginosa. The results demonstrate a new QS regulation mechanism via the efflux system MexAB- OprM in P. aeruginosa.
Epidemiological characteristics and societal burden of varicella zoster virus in the Netherlands
Authors: Pierik Jorien GJ , Gumbs Pearl D , Fortanier Sander AC , Van Steenwijk Pauline CE , Postma Maarten J
Published: May 2012

Background

Varicella and herpes zoster are both caused by varicella zoster virus (VZV) infection or reactivation and may lead to complications associated with a (severe) societal burden. Because the epidemiology of VZV-related diseases in the Netherlands remains largely unknown or incomplete, the main objective of this study was to study the primary care incidence, associated complications and health care resource use.

Methods

We investigated the incidence of VZV complications in the Dutch general practitioner (GP) practices and pharmacies in a retrospective population-based cohort study (2004–2008) based on longitudinal GP data including free text fields, hospital referral and discharge letters from approximately 165,000 patients.

Results

The average annual incidence of varicella GP-consultations was 51.5 per 10,000 (95% CI 44.4-58.7) overall; 465.5 per 10,000 for 0–1 year-olds; 610.8 per 10,000 for 1–4 year-olds; 153.5 per 10,000 for 5–9 year-olds; 8,3 per 10,000 for >10 year olds. When only ICPC coded diagnoses were analyzed the incidence was 27% lower. The proportion of complications among varicella patients was 34.9%. Most frequently complications were upper respiratory tract infections. Almost half of the varicella patients received medication. The referral rate based on GP consultations was 1.7%. The average annual incidence of herpes zoster GP-consultations was 47.5 per 10,000 (95% CI 40.6-54.4). The incidence increased with age; 32.8 per 10,000 for <60 year-olds; 93.1 per 10,000 for 60–64 year-olds and 113.2 per 10,000 for >65 year olds. When estimating herpes zoster incidence only on ICPC coded information, the incidence was 28% lower. The complication rate of herpes zoster was 32.9%. Post herpetic neuralgia was seen most often. Of patients diagnosed with herpes zoster 67.8% received medication. The referral rate based on GP consultations was 3.5%.

Conclusions

For varicella the highest incidence of GP-consultations was found in 1–4 year-olds, for herpes zoster in the >65 years olds. The occurrence of complications was not age-dependent but varies per complication. When estimating incidence of VZV-related diseases in primary care, based on diagnostic codes only, one should be aware of a gross underestimation of the incidence. Our analysis may have important implications for the outcomes of upcoming cost-effectiveness analyses on VZV vaccination.
Paralemmin-1 is over-expressed in estrogen-receptor positive breast cancers
Authors: Turk Casey M , Fagan-Solis Katerina D , Williams Kristin E , Gozgit Joseph M , Smith-Schneider Sallie , Marconi Sharon A , Otis Christopher N , Crisi Giovanna M , Anderton Douglas L , Kilimann Manfred W , Arcaro Kathleen F
Published: May 2012

Background

Paralemmin-1 is a phosphoprotein lipid-anchored to the cytoplasmic face of membranes where it functions in membrane dynamics, maintenance of cell shape, and process formation. Expression of paralemmin-1 and its major splice variant (Δ exon 8) as well as the extent of posttranslational modifications are tissue- and development-specific. Paralemmin-1 expression in normal breast and breast cancer tissue has not been described previously.

Results

Paralemmin-1 mRNA and protein expression was evaluated in ten breast cell lines, 26 primary tumors, and 10 reduction mammoplasty (RM) tissues using real time RT-PCR. Paralemmin-1 splice variants were assessed in tumor and RM tissues using a series of primers and RT-PCR. Paralemmin-1 protein expression was examined in cell lines using Western Blots and in 31 ductal carcinomas in situ, 65 infiltrating ductal carcinomas, and 40 RM tissues using immunohistochemistry. Paralemmin-1 mRNA levels were higher in breast cancers than in RM tissue and estrogen receptor (ER)-positive tumors had higher transcript levels than ER-negative tumors. The Δ exon 8 splice variant was detected more frequently in tumor than in RM tissues. Protein expression was consistent with mRNA results showing higher paralemmin-1 expression in ER-positive tumors.

Conclusions

The differential expression of paralemmin-1 in a subset of breast cancers suggests the existence of variation in membrane dynamics that may be exploited to improve diagnosis or provide a therapeutic target.
Fixed point theory for cyclic generalized contractions in partial metric spaces
Authors: Agarwal Ravi P , Alghamdi Maryam A , Shahzad Naseer
Published: May 2012

In this article, we give some fixed point theorems for mappings satisfying cyclical generalized contractive conditions in complete partial metric spaces.
The prototype foamy virus protease is active independently of the integrase domain
Authors: Spannaus Ralf , Hartl Maximilian J , Wöhrl Birgitta M , Rethwilm Axel , Bodem Jochen
Published: May 2012

Background

Recently, contradictory results on foamy virus protease activity were published. While our own results indicated that protease activity is regulated by the viral RNA, others suggested that the integrase is involved in the regulation of the protease.

Results

To solve this discrepancy we performed additional experiments showing that the protease-reverse transcriptase (PR-RT) exhibits protease activity in vitro and in vivo, which is independent of the integrase domain. In contrast, Pol incorporation, and therefore PR activity in the viral context, is dependent on the integrase domain. To further analyse the regulation of the protease, we incorporated Pol in viruses by expressing a GagPol fusion protein, which supported near wild-type like infectivity. A GagPR-RT fusion, lacking the integrase domain, also resulted in wild-type like Gag processing, indicating that the integrase is dispensable for viral Gag maturation. Furthermore, we demonstrate with a trans-complementation assays that the PR in the context of the PR-RT protein supports in trans both, viral maturation and infectivity.

Conclusion

We provide evidence that the FV integrase is required for Pol encapsidation and that the FV PR activity is integrase independent. We show that an active PR can be encapsidated in trans as a GagPR-RT fusion protein.
Sensory nerve action potentials and sensory perception in women with arthritis of the hand
Authors: Calder Kristina M , Martin Alison , Lydiate Jessica , MacDermid Joy C , Galea Victoria , MacIntyre Norma J
Published: May 2012

Background

Arthritis of the hand can limit a person’s ability to perform daily activities. Whether or not sensory deficits contribute to the disability in this population remains unknown. The primary purpose of this study was to determine if women with osteoarthritis (OA) or rheumatoid arthritis (RA) of the hand have sensory impairments.

Methods

Sensory function in the dominant hand of women with hand OA or RA and healthy women was evaluated by measuring sensory nerve action potentials (SNAPs) from the median, ulnar and radial nerves, sensory mapping (SM), and vibratory and current perception thresholds (VPT and CPT, respectively) of the second and fifth digits.

Results

All SNAP amplitudes were significantly lower for the hand OA and hand RA groups compared with the healthy group (p < 0.05). No group differences were found for SNAP conduction velocities, SM, VPT, and CPT.

Discussion

We propose, based on these findings, that women with hand OA or RA may have axonal loss of sensory fibers in the median, ulnar and radial nerves. Less apparent were losses in conduction speed or sensory perception.
STEPS: efficient simulation of stochastic reaction–diffusion models in realistic morphologies
Authors: Hepburn Iain , Chen Weiliang , Wils Stefan , De Schutter Erik
Published: May 2012

Background

Models of cellular molecular systems are built from components such as biochemical reactions (including interactions between ligands and membrane-bound proteins), conformational changes and active and passive transport. A discrete, stochastic description of the kinetics is often essential to capture the behavior of the system accurately. Where spatial effects play a prominent role the complex morphology of cells may have to be represented, along with aspects such as chemical localization and diffusion. This high level of detail makes efficiency a particularly important consideration for software that is designed to simulate such systems.

Results

We describe STEPS, a stochastic reaction–diffusion simulator developed with an emphasis on simulating biochemical signaling pathways accurately and efficiently. STEPS supports all the above-mentioned features, and well-validated support for SBML allows many existing biochemical models to be imported reliably. Complex boundaries can be represented accurately in externally generated 3D tetrahedral meshes imported by STEPS. The powerful Python interface facilitates model construction and simulation control. STEPS implements the composition and rejection method, a variation of the Gillespie SSA, supporting diffusion between tetrahedral elements within an efficient search and update engine. Additional support for well-mixed conditions and for deterministic model solution is implemented. Solver accuracy is confirmed with an original and extensive validation set consisting of isolated reaction, diffusion and reaction–diffusion systems. Accuracy imposes upper and lower limits on tetrahedron sizes, which are described in detail. By comparing to Smoldyn, we show how the voxel-based approach in STEPS is often faster than particle-based methods, with increasing advantage in larger systems, and by comparing to MesoRD we show the efficiency of the STEPS implementation.

Conclusion

STEPS simulates models of cellular reaction–diffusion systems with complex boundaries with high accuracy and high performance in C/C++, controlled by a powerful and user-friendly Python interface. STEPS is free for use and is available at http://steps.sourceforge.net/
Oral Ezatiostat HCl (TLK199) and Myelodysplastic syndrome: A case report of sustained hematologic response following an abbreviated exposure
Authors: Quddus Fahd , Clima Jessica , Seedham Helen , Sajjad Ghulam , Galili Naomi , Raza Azra
Published: May 2012

Treatment options for patients with lower risk non-del(5q) myelodysplastic syndromes (MDS) who fail erythroid stimulating agents are restricted to one of the hypomethylating drugs with an expected response rate of ~50%. Ezatiostat HCl, an agent with the potential for producing multi-lineage responses in this population is currently in clinical investigation phase. This case report describes a 77 year old male who received less than two cycles of therapy with ezatiostat HCl which had to be aborted due to intolerable side effects, but which produced a sustained normalization of all three blood counts. This trilineage response has now lasted for more than a year. Interestingly, the patient began with a del(5q) abnormality and responded briefly to lenalidomide. Upon relapse of the anemia, a bone marrow showed the disappearance of the del(5q) but the appearance of a new clonal abnormality t(2;3). Given that the patient had a complete cytogenetic response to a truncated exposure to lenalidomide followed by a trilineage response to an even briefer course of ezatiostat HCl suggests a potential role for ezatiostat HCl in del(5q) patients who relapse following lenalidomide.
Current research in perineural invasion of cholangiocarcinoma
Authors: Shen Fang-Zhen , Zhang Bing-Yuan , Feng Yu-Jie , Jia Zhuo-Xia , An Bing , Liu Chang-Chang , Deng Xi-Yun , Kulkarni Anil D , Lu Yun
Published: May 2012

Background

Perineural invasion is a common path for cholangiocarcinoma (CCA) metastasis, and it is highly correlated with postoperative recurrence and poor prognosis. It is often an early event in a disease that is commonly diagnosed in advanced stages, and thus it could offer a timely therapeutic and diagnostic target if better understood. This article systematically reviews the progress of CCA neural invasion-related molecules.

Methods

Studies were identified by searching MEDLINE and PubMed databases for articles from January 1990 to December 2009, using the keywords "cholangiocarcinoma," "perineural invasion," "nerve growth factor"(NGF), "neural cell adhesion molecule" (NCAM), "matrix metalloproteinase"(MMP), "neurotransmitter," "acetylcholine" (Ach), and "transforming growth factor" (TGF)." Additional papers and book chapters were identified by a manual search of references from the key articles.

Results

From above we found that the molecules NGF, NCAM, MMP, Ach and TGF may have prognostic significance in, and offer clues to the mechanism of CCA neural invasion.

Conclusions

Cholangiocarcinoma's increasing worldwide incidence is especially poignant in view of both the lacking effective therapies, and the fact that it is commonly diagnosed in advanced stages. As CCA neural invasion often appears early, more complete characterization of its molecular pathology could lead to the identification of targets for the diagnosis and therapy of this devastating malignancy.
Impact on life expectancy of late diagnosis and treatment of HIV‐1 infected individuals: UK CHIC
Authors: May MT , Gompels M , Sabin CA
Published: May 2012

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Vitamin D and HIV: shine a light
Authors: Currier J
Published: May 2012

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Low‐level residual viremia and risk of virological failure
Authors: Cologni G , Soavi L , Leone S , Valenti D , Callegaro A , Gregis G , Suter F , Maggiolo F
Published: May 2012

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Continuing burden of HIV late presenters in the North East of England 2009
Authors: Premchand N , Golds K , Tan PY , Bittiner I , Sanker N , Ong ELC
Published: May 2012

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Survey of HNPCC Management Analysis of Responses from 18 International Cancer Centres
Authors: Chow Elizabeth , Macrae Finlay , Burn John ,   respondents from 18 international ICG-HNPCC Familial Cancer Clinics
Published: May 2012

Eighteen international cancer centres responded to a questionnaire designed to determine clinic practices regarding the management of Hereditary Non-Polyposis Colorectal Cancer (HNPCC). Areas covered include definition, clinical intakes, pre-genetic testing for microsatellite instability (MSI) or expression of mismatch repair (MMR) genes by immunohistochemistry (IHC), mutational analysis, consent practices, counselling, surveillance planning, and surgical decision making. In the absence of a firm evidence base, some management practices were variable, with local access to funding and other resources being influential. More consistent responses were evident for management practices with a stronger evidence base from previous clinical research. This document provides important information to guide the management of HNPCC patients, allow comparisons to be made between the approaches of various clinics to HNPCC families, and define management issues that need to be addressed in clinical research.
Hereditary Colorectal Cancer Syndromes in Hong Kong: a Registry's Perspective
Authors: Ho Judy WC , Wei Rockson , Chan Emily MS
Published: May 2012

Established in 1995, the Hereditary Gastrointestinal Cancer Registry aimed at cancer prevention due to hereditary colorectal cancer syndromes in Hong Kong through early detection, timely treatment, education and ongoing research. This article details the history, structure and work of the Registry. A summary is also provided on the results of various research work conducted by the Registry which facilitates the clinical management of hereditary colorectal cancer syndromes in Hong Kong Chinese families.
Hereditary Colorectal Cancer in China
Authors: Shu Zheng , Yanqin Huang , Ying Yuan
Published: May 2012

The purpose of this article is to review basic research as well as clinical studies on Chinese hereditary colorectal cancer. Hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) accounts for 2.2% of all colorectal cancer, and Chinese criteria for suspected HNPCC have been developed. Germline mutations as well as large genomic rearrangements of mismatch repair (MMR) genes are responsible for this syndrome. Gastric cancer is the second most common cancer in Chinese HNPCC patients. Contrary to sporadic colorectal cancer in the Chinese population, HNPCC does not typically present with rectal cancer. Incidence of familial adenomatous polyposis (FAP) in China is approximately 1.5/100,000. Polyps in Chinese FAP patients can emerge as early as 16 months old, but malignant transformation usually occurs in the third and fourth decade. Total resection of the colon and rectum is necessary in FAP patients. For unresectable duodenal polyps, chemopreventive agents may be used.
Quorums-based Replication of Multimedia Objects in Distributed Systems
Authors: Ohkawara Tadateru , Aikebaier Ailixier , Enokido Tomoya , Takizawa Makoto
Published: May 2012

Background

Multimedia objects like music and movies are distributed to peers through downloading and caching in peer-to-peer (P2P) overlay networks. In this paper, we consider multimedia objects which are characterized in terms of not only data structure but also quality of service (QoS) like frame rate and number of colours. For example, there are a pair of replicas o
i
and o
j
of a fully coloured movie object o. Here, a content of a replica o
i
is changed by adding a subobject but another replica o
j
is not changed. On the other hand, the colour of the replica o
j
is changed with monochromatic one but not in the replica o
i
. This means, the replica o
i
is newer than the replica o
j
with respect to the content but is older than o
j
with respect to QoS. Thus, replicas of a multimedia object are partially ordered in terms of newness of not only content but also QoS parameters.

Methods

In traditional quorum-based (QB) protocols, replicas are totally ordered just in terms of newness of content. We discuss a multimedia quorum-based (MQB) protocol to synchronize multiple replicas to make consistent on the basis of the newness-precedent relation of replicas. Here, the replicas are ordered in vectors of version counters of content and QoS parameters. Every replica in a quorum is not updated for QoS operations to reduce the communication overhead. We evaluate the MQB protocol in terms of communication overhead and show the communication overhead can be reduced in the MQB protocol compared with the traditional QB protocol.

Conclusions

We discussed the multimedia quorum-based (MQB) protocol to keep replicas of a multimedia object mutually consistent. We evaluated the MQB protocol in terms of the total volume of data transmitted among the replicas. Then, we showed the total amount of data transmitted can be reduced in the MQB protocol compared with the traditional quorum-based (QB) protocol.
Fueling the flame: bioenergy couples metabolism and inflammation
Authors: Liu Tie Fu , Brown Candice M , El Gazzar Mohamed , McPhail Linda , Millet Patrick , Rao Anuradha , Vachharajani Vidula T , Yoza Barbara K , McCall Charles E
Published: May 2012

Review on how the integration of bioenergetics and metabolism controls inflammation progression.

We review the emerging concept that changes in cellular bioenergetics concomitantly reprogram inflammatory and metabolic responses. The molecular pathways of this integrative process modify innate and adaptive immune reactions associated with inflammation, as well as influencing the physiology of adjacent tissue and organs. The initiating proinflammatory phase of inflammation is anabolic and requires glucose as the primary fuel, whereas the opposing adaptation phase is catabolic and requires fatty acid oxidation. The fuel switch to fatty acid oxidation depends on the sensing of AMP and NAD+ by AMPK and the SirT family of deacetylases (e.g., SirT1, -6, and -3), respectively, which couple inflammation and metabolism by chromatin and protein reprogramming. The AMP-AMPK/NAD+-SirT axis proceeds sequentially during acute systemic inflammation associated with sepsis but ceases during chronic inflammation associated with diabetes, obesity, and atherosclerosis. Rebalancing bioenergetics resolves inflammation. Manipulating cellular bioenergetics is identifying new ways to treat inflammatory and immune diseases.
Temporal control of neural crest lineage generation by Wnt/β-catenin signaling
Authors: Hari Lisette , Miescher Iris , Shakhova Olga , Suter Ueli , Chin Lynda , Taketo Makoto , Richardson William D. , Kessaris Nicoletta , Sommer Lukas
Published: May 2012

Wnt/β-catenin signaling controls multiple steps of neural crest development, ranging from neural crest induction, lineage decisions, to differentiation. In mice, conditional β-catenin inactivation in premigratory neural crest cells abolishes both sensory neuron and melanocyte formation. Intriguingly, the generation of melanocytes is also prevented by activation of β-catenin in the premigratory neural crest, which promotes sensory neurogenesis at the expense of other neural crest derivatives. This raises the question of how Wnt/β-catenin signaling regulates the formation of distinct lineages from the neural crest. Using various Cre lines to conditionally activate β-catenin in neural crest cells at different developmental stages, we show that neural crest cell fate decisions in vivo are subject to temporal control by Wnt/β-catenin. Unlike in premigratory neural crest, β-catenin activation in migratory neural crest cells promotes the formation of ectopic melanoblasts, while the production of most other lineages is suppressed. Ectopic melanoblasts emerge at sites of neural crest target structures and in many tissues usually devoid of neural crest-derived cells. β-catenin activation at later stages in glial progenitors or in melanoblasts does not lead to surplus melanoblasts, indicating a narrow time window of Wnt/β-catenin responsiveness during neural crest cell migration. Thus, neural crest cells appear to be multipotent in vivo both before and after emigration from the neural tube but adapt their response to extracellular signals in a temporally controlled manner.
Cytoskeletal changes in actin and microtubules underlie the developing surface mechanical properties of sensory and supporting cells in the mouse cochlea
Authors: Szarama Katherine B. , Gavara Núria , Petralia Ronald S. , Kelley Matthew W. , Chadwick Richard S.
Published: May 2012

Correct patterning of the inner ear sensory epithelium is essential for the conversion of sound waves into auditory stimuli. Although much is known about the impact of the developing cytoskeleton on cellular growth and cell shape, considerably less is known about the role of cytoskeletal structures on cell surface mechanical properties. In this study, atomic force microscopy (AFM) was combined with fluorescence imaging to show that developing inner ear hair cells and supporting cells have different cell surface mechanical properties with different developmental time courses. We also explored the cytoskeletal organization of developing sensory and non-sensory cells, and used pharmacological modulation of cytoskeletal elements to show that the developmental increase of hair cell stiffness is a direct result of actin filaments, whereas the development of supporting cell surface mechanical properties depends on the extent of microtubule acetylation. Finally, this study found that the fibroblast growth factor signaling pathway is necessary for the developmental time course of cell surface mechanical properties, in part owing to the effects on microtubule structure.
RBE controls microRNA164 expression to effect floral organogenesis
Authors: Huang Tengbo , López-Giráldez Francesc , Townsend Jeffrey P. , Irish Vivian F.
Published: May 2012

The establishment and maintenance of organ boundaries are vital for animal and plant development. In the Arabidopsis flower, three microRNA164 genes (MIR164a, b and c) regulate the expression of CUP-SHAPED COTYLEDON1 (CUC1) and CUC2, which encode key transcriptional regulators involved in organ boundary specification. These three miR164 genes are expressed in distinct spatial and temporal domains that are crucial for their function. Here, we show that the C2H2 zinc finger transcriptional repressor encoded by RABBIT EARS (RBE) regulates the expression of all three miR164 genes. Furthermore, we demonstrate that RBE directly interacts with the promoter of MIR164c and negatively regulates its expression. We also show that the role of RBE in sepal and petal development is mediated in part through the concomitant regulation of the CUC1 and CUC2 gene products. These results indicate that one role of RBE is to fine-tune miR164 expression to regulate the CUC1 and CUC2 effector genes, which, in turn, regulate developmental events required for sepal and petal organogenesis.
The bHLH transcription factor Tcf21 is required for lineage-specific EMT of cardiac fibroblast progenitors
Authors: Acharya Asha , Baek Seung Tae , Huang Guo , Eskiocak Banu , Goetsch Sean , Sung Caroline Y. , Banfi Serena , Sauer Marion F. , Olsen Gregory S. , Duffield Jeremy S. , Olson Eric N. , Tallquist Michelle D.
Published: May 2012

The basic helix-loop-helix (bHLH) family of transcription factors orchestrates cell-fate specification, commitment and differentiation in multiple cell lineages during development. Here, we describe the role of a bHLH transcription factor, Tcf21 (epicardin/Pod1/capsulin), in specification of the cardiac fibroblast lineage. In the developing heart, the epicardium constitutes the primary source of progenitor cells that form two cell lineages: coronary vascular smooth muscle cells (cVSMCs) and cardiac fibroblasts. Currently, there is a debate regarding whether the specification of these lineages occurs early in the formation of the epicardium or later after the cells have entered the myocardium. Lineage tracing using a tamoxifen-inducible Cre expressed from the Tcf21 locus demonstrated that the majority of Tcf21-expressing epicardial cells are committed to the cardiac fibroblast lineage prior to initiation of epicardial epithelial-to-mesenchymal transition (EMT). Furthermore, Tcf21 null hearts fail to form cardiac fibroblasts, and lineage tracing of the null cells showed their inability to undergo EMT. This is the first report of a transcription factor essential for the development of cardiac fibroblasts. We demonstrate a unique role for Tcf21 in multipotent epicardial progenitors, prior to the process of EMT that is essential for cardiac fibroblast development.
Inositol polyphosphate 5-phosphatase-controlled Ins(1,4,5)P3/Ca2+ is crucial for maintaining pollen dormancy and regulating early germination of pollen
Authors: Wang Yuan , Chu Yu-Jia , Xue Hong-Wei
Published: May 2012

Appropriate pollen germination is crucial for plant reproduction. Previous studies have revealed the importance of dehydration in maintaining pollen dormancy; here, we show that phosphatidylinositol pathway-controlled Ins(1,4,5)P3/Ca2+ levels are crucial for maintaining pollen dormancy in Arabidopsis thaliana. An interesting phenotype, precocious pollen germination within anthers, results from a disruption of inositol polyphosphate 5-phosphatase 12 (5PT12). The knockout mutant 5pt12 has normal early pollen development and pollen dehydration, and exhibits hypersensitive ABA responses, indicating that precocious pollen germination is not caused either by abnormal dehydration or by suppressed ABA signaling. Deficiency of 5PT13 (a close paralog of 5PT12) synergistically enhances precocious pollen germination. Both basal Ins(1,4,5)P3 levels and endogenous Ca2+ levels are elevated in pollen from 5pt12 mutants, and 5pt12 5pt13 double mutants show an even higher precocious germination rate along with much higher levels of Ins(1,4,5)P3/Ca2+. Strikingly, exogenous Ca2+ stimulates the germination of wild-type pollen at floral stage 12, even in very low humidity, both in vitro and in vivo, and treatment with BAPTA, a [Ca2+]cyt inhibitor, reduces the precocious pollen germination rates of 5pt12, 5pt13 and 5pt12 5pt13 mutants. These results indicate that the increase in the levels of Ins(1,4,5)P3/Ca2+ caused by deficiency of inositol polyphosphate 5-phosphatases is sufficient to break pollen dormancy and to trigger early germination. The study reveals that independent of dehydration, the control of Ins(1,4,5)P3/Ca2+ levels by Inositol polyphosphate 5-phosphatases is crucial for maintaining pollen dormancy.
Imaging findings of ruptured abdominal and pelvic tumors
Authors: Kim Sang Won , Kim Hyun Cheol , Yang Dal Mo
Published: May 2012

A variety of abdominal and pelvic tumors can present with rupture leading to hemoperitoneum/hemoretroperitoneum or peritonitis. Imaging plays an important role in the diagnosis of hemorrhage or peritonitis as well as in the detection of ruptured tumors or organs. In this article, we illustrate the imaging findings of ruptured tumors arising in the abdominal and pelvic organs while excluding those of ruptured tumors arising in the stomach and intestines. It is important for the radiologists to understand the mechanisms involved in tumor rupture and recognize the imaging features of ruptured tumors according to the organs involved because this will permit the exact diagnosis of ruptured tumors, thereby facilitating prompt and effective treatment.
Benign regional lymph nodes in gastric cancer on multidetector row CT
Authors: Park Hee Sun , Kim Young Jun , Ko Su Yeon , Yoo Moon-Won , Lee Kyung Yung , Jung Sung-Il , Jeon Hae Jeong
Published: May 2012

Background

Benign regional lymph nodes (LNs) are sometimes enlarged in gastric cancer patients due to reactive or inflammatory changes. Frequently these enlarged LNs can mimic LN metastasis and lead to overstaging.

Purpose

To assess frequency of benign regional LNs in gastric cancer patients compared with that in a healthy population and to assess the frequency of benign regional LNs in gastric cancer according to T-staging.

Material and Methods

Between August 2005 and June 2009, 177 patients with surgically proven gastric cancer without LN metastasis (T anyN0M0) who had previously undergone preoperative multidetector row CT (MDCT) and 168 healthy patients who visited the healthcare center and underwent an abdominal MDCT were included in this retrospective study. An abdominal radiologist evaluated the distribution of regional LNs and measured the short diameter of LNs ≥6 mm, ≥8 mm, and ≥10 mm. The number of enlarged benign LNs was compared between the two groups, and the distribution of LN with regard to T-stage of gastric cancer was also evaluated.

Results

At least one LN ≥6 mm, ≥8 mm, and ≥10 mm was detected in 64.4% (114/177), 22.0% (39/177), and 4.0% (7/177) of patients in the gastric cancer group, respectively, compared to 29.8% (50/168), 4.2% (7/168), and 0% of patients in the healthy group, respectively. The difference between the two groups was statistically significant ( P <0.0001). The LN ≥8 mm was found in 14.9% (20/134) in early gastric cancer (T1), and 44.2% (19/43) in advanced cancer (T2 or higher); the difference was statistically significant ( P = 0.0002). However, the frequency of LN ≥6 mm in mucosal cancer (T1a) and submucosal cancer (T2b) was not significantly different, regardless of its size.

Conclusion

Benign regional LNs ≥6 mm are more frequently detected in gastric cancer patients than in a healthy population and in advanced gastric cancer than in early cancer.
Human papillomavirus infections in women with clinical gynaecological diseases in southwest China
Authors: Zhu Y , Ding X , Wang Y , Gao J , Shen M , He J
Published: May 2012

The aim of this study was to determine the prevalence of human papillomavirus (HPV) infections in women with different gynaecological diseases (GDs) and ages in southwest China. With the assay of reverse dot blot, a total of 5544 cervical samples, including 1008 normal and 4536 abnormal specimens from women with GDs, were assayed for HPV detection. For the normal group, 20.2% (204/1008) tested positive for HPV, of which 40.2% (82/204) were high-risk (HR-HPV) genotypes. In the 4536 abnormal samples, 1569 women (34.6%) tested positive for HPV: 73.5% (1153/1569) had a single infection, 17.7% (277/1569) dual infection and 8.8% (138/1569) multiple HPV infection. Of 1569 HPV-positive specimens, 58.7% (921/1569) were infected with only HR-HPV genotypes. Significant differences in HPV infections were found among women of different ages ( P < 0.01), number of pregnancies ( P < 0.01), GDs ( P < 0.01) and age at first sex ( P < 0.01). In the present study, we found a high prevalence of HPV infection in women with GDs in southwest China. In addition to HPV types 16 and 18, a significant proportion of other HR-HPV genotypes were detected in this population.
Detection of the Treponema pallidum gene and variation of treponemal DNA load before and after therapy
Authors: Wang L N , Li J , Huang W , Zheng H Y , Zuo Y G , Liu Y X , Wang X F , Liu X R
Published: May 2012

We explored a genetic detection method for Treponema pallidum (TP) in the peripheral blood of infected patients to compare the loads of treponemal DNA before and after therapy and to see if this new technique enabled assessment of therapeutic effect and detection of serum resistance. Polymerase chain reaction was used for a qualitative detection of TP DNA in peripheral blood and then a semiquantitative method was adopted to estimate the load of TP DNA in blood, both before and after treatment of syphilis. Among 30 untreated patients, three cases were TP DNA-positive. Among 42 treated patients with demonstrated serum resistance, three cases were TP DNA-positive. Five cases in which the rapid plasma reagin had become negative had no detectable TP DNA in their peripheral blood. The TP DNA load in blood after treatment was significantly lower than that before therapy. We conclude that the detection of TP DNA in peripheral blood of TP-infected patients is not yet sufficiently sensitive, but we observed that TP DNA load declines significantly after treatment.
Upper gastrointestinal bleeding in a young female with AIDS: a case report
Authors: Szajerka T , Jabłecki J
Published: May 2012

Upper gastrointestinal haemorrhage (UGIH) is a surprisingly common condition in patients with AIDS (PWAs), affecting at least 6%. With the growing number of PWAs and their increasing life span, UGIH will certainly gain importance as a diagnostic and therapeutic challenge to health-care professionals, especially in central and eastern Europe because of the AIDS epidemics rapidly developing in that region. With the scarcity of reported cases, lack of management guidelines of UGIH in PWAs, and limited therapeutic possibilities in developing countries, important therapeutic problems should be anticipated. We present a case of UGIH in a female PWA due to ketoprofen overuse, successfully managed with conservative treatment.
Atypical progressive multifocal leukoencephalopathy in HIV with a high CD4 count: the use of magnetic resonance imaging plus spectrometry studies
Authors: Manfredi R , Piergentili B , Marinacci G , Calza L
Published: May 2012

Progressive multifocal leukoencephalopathy (PML) is still a underinvestigated central nervous system infection, often linked to HIV-related immunodeficiency. We present an unusual case report characterized by motor involvement, which occurred as the first AIDS-defining event in the absence of appreciable immunodeficiency in a patient with previously undiagnosed HIV infection, who was also assessed by a functional–metabolic magnetic resonance imaging technique (MRI–spectrometry). A 45-year-old patient had HIV infection detected after the appearance of motor abnormalities, in the absence of other signs or symptoms. No significant immunodeficiency was found (initial CD4+ lymphocyte count of 566 cells/µL), and HIV viral load was 24,000 RNA copies/mL. Combination antiretroviral therapy was started with lamivudine, abacavir and lopinavir/ritonavir, with subsequent addition of efavirenz and enfuvirtide. Elevated cerebrospinal fluid levels of JC virus (JCV) (11,668 copies/µL) and consistent neuroradiological findings at contrast-enhanced computed tomography and MRI scans confirmed a diagnosis of PML. Despite the aggressive therapeutic approach, which achieved undetectable HIV viraemia, a CD4+ count above 700 cells/µL and disappearance of JCV after 20 days, the neurological motor involvement rapidly deteriorated, yet associated cognitive impairment never occurred. Clinical and neuroradiological deterioration occurred, and our patient died five months after the diagnosis due to respiratory failure. Combined MRI–spectrometry studies performed 10 days before death included proton (1H) spectrometry, and an MRI study-calculation of water diffusion and anisotropy: through this innovative technique combining morphological and metabolic findings, multiple abnormalities involving the subtentorial white matter were detected (with multiple encephalic trunk and ponto-bulbar lesions), which usually are not part of the PML course.
AIDS-associated Kaposi's sarcoma of the conjunctiva in a woman
Authors: Bavishi A , Ashraf A , Lee L
Published: May 2012

Conjunctival involvement by AIDS-associated Kaposi's sarcoma (KS) is rare, more so in women. We present a case of a 34-year-old African-American woman with AIDS, who was admitted to our hospital and diagnosed with KS of the conjunctiva. To date there are only a few reported cases of AIDS-associated conjunctival KS in the literature. This case is the first case of AIDS-associated conjunctival KS in an African-American woman and emphasizes the importance of considering KS as a differential diagnosis of the conjunctival mass in HIV-positive patients.
Assessing adherence in Thai patients taking combination antiretroviral therapy
Authors: Kerr S J , Avihingsanon A , Putcharoen O , Chetchotisakd P , Layton M , Ubolyam S , Ruxrungtham K , Cooper D A , Phanuphak P , Duncombe C
Published: May 2012

In settings where medications and viral load (VL) monitoring are limited by cost, clinicians need reliable ways to assess patient adherence to therapy. We assessed sensitivity and specificity of two self-reported adherence tools (a visual analogue scale [VAS] and the CASE [Center for Adherence Support Evaluation] adherence index), against a standard of detectable VL, with 288 patients from three sites in Thailand. We also assessed predictors of non-adherence. The sensitivity and specificity of the VAS <95% and CASE adherence index ≤11 against a VL >50 copies/mL were 26% and 90%, 19% and 95%, respectively. Against a VL ≥1000 copies/mL sensitivities increased to 55% and 36%, respectively, and specificities were unchanged. Attending a clinic not staffed by HIV specialists (odds ratio [OR] 3.14; 95% confidence interval [CI] 1.19–8.34) and being educated to primary school level or less (OR 2.24; 95% CI 1.01–4.94) were associated with self-reported adherence <95% on the VAS in multivariate analysis. Adherence assessed by the VAS was a more accurate predictor of detectable VL. Policy-makers in resource-limited settings should ensure that treatment centres are staffed with well-trained personnel aware of the importance of good patient adherence.
Management of Neisseria gonorrhoeae infection over 12 months in a genitourinary medicine setting against British Association for Sexual Health and HIV auditable outcome measures
Authors: Bruck P E , Robertson C , Allan P S
Published: May 2012

Audit of gonorrhoea management resulted in recognition of a need to change the clinic protocol for first-line antibiotic therapy and also in improvements in clinic recording of written information given to patients and the outcome of contact tracing.