bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of PknB Kinase in Antibiotic Resistance and Virulence in Community-Acquired Methicillin-Resistant
Staphylococcus aureus
Strain USA300
Authors: Tamber Sandeep , Schwartzman Joseph , Cheung Ambrose L. 
Published: June 2010

ABSTRACT

The regulation of cellular processes by eukaryote-like serine/threonine kinases is widespread in bacteria. In the last 2 years, several studies have examined the role of serine/threonine kinases in
Staphylococcus aureus
on cell wall metabolism, autolysis, and virulence, mostly in
S. aureus
laboratory isolates in the 8325-4 lineage. In this study, we showed that the
pknB
gene (also called
stk1
) of methicillin-resistant
S. aureus
(MRSA) strain COL and the community-acquired MRSA (CA-MRSA) strain USA300 is involved in cell wall metabolism, with the
pknB
mutant exhibiting enhanced sensitivity to β-lactam antibiotics but not to other classes of antibiotics, including aminoglycosides, ciprofloxacin, bactrim, and other types of cell wall-active agents (e.g., vancomycin and bacitracin). Additionally, the
pknB
mutant of USA300 was found to be more resistant to Triton X-100-induced autolysis and also to lysis by lysostaphin. We also showed that
pknB
is a positive regulator of
sigB
activity, resulting in compromise in its response to heat and oxidative stresses. In association with reduced
sigB
activity, the expression levels of RNAII and RNAIII of
agr
and the downstream effector
hla
are upregulated while
spa
expression is downmodulated in the
pknB
mutant compared to the level in the parent. Consistent with an enhanced
agr
response
in vitro
, virulence studies of the
pknB
mutant of USA300 in a murine cutaneous model of infection showed that the mutant was more virulent than the parental strain. Collectively, our results have linked the
pknB
gene in CA-MRSA to antibiotic resistance,
sigB
activity, and virulence and have highlighted important differences in
pknB
phenotypes (virulence and
sigB
activity) between laboratory isolates and the prototypic CA-MRSA strain USA300.
Practical performance models for complex, popular applications
Authors: Thereska Eno , Doebel Bjoern , Zheng Alice X. , Nobel Peter 
Published: June 2010

Perhaps surprisingly, no practical performance models exist for popular (and complex) client applications such as Adobe's Creative Suite, Microsoft's Office and Visual Studio, Mozilla, Halo 3, etc. There is currently no tool that automatically answers program developers', IT administrators' and end-users' simple what-if questions like "what happens to the performance of my favorite application X if I upgrade from Windows Vista to Windows 7?". This paper describes our approach towards constructing practical, versatile performance models to address this problem. The goal is to have these models be useful for application developers to help expand application testing coverage and for IT administrators to assist with understanding the performance consequences of a software, hardware or configuration change.
This paper's main contributions are in system building and performance modeling. We believe we have built applications that are easier to model because we have proactively instrumented them to export their state and associated metrics. This application-specific monitoring is always on and interesting data is collected from real, "in-the-wild" deployments. The models we are experimenting with are based on statistical techniques. They require no modifications to the OS or applications beyond the above instrumentation, and no explicit a priori model on how an OS or application should behave. We are in the process of learning from models we have constructed for several Microsoft products, including the Office suite, Visual Studio and Media Player. This paper presents preliminary findings from a large user deployment (several hundred thousand user sessions) of these applications that show the coverage and limitations of such models. These findings pushed us to move beyond averages/means and go into some depth into why client application performance has an inherently large variance.
A mean field model of work stealing in large-scale systems
Authors: Gast Nicolas , Bruno Gaujal 
Published: June 2010

In this paper, we consider a generic model of computational grids, seen as several clusters of homogeneous processors. In such systems, a key issue when designing efficient job allocation policies is to balance the workload over the different resources.
We present a Markovian model for performance evaluation of such a policy, namely work stealing (idle processors steal work from others) in large-scale heterogeneous systems. Using mean field theory, we show that when the size of the system grows, it converges to a system of deterministic ordinary differential equations that allows one to compute the expectation of performance functions (such as average response times) as well as the distributions of these functions.
Transparent, lightweight application execution replay on commodity multiprocessor operating systems
Authors: Laadan Oren , Viennot Nicolas , Nieh Jason 
Published: June 2010

We present Scribe, the first system to provide transparent, low-overhead application record-replay and the ability to go live from replayed execution. Scribe introduces new lightweight operating system mechanisms, rendezvous and sync points, to efficiently record nondeterministic interactions such as related system calls, signals, and shared memory accesses. Rendezvous points make a partial ordering of execution based on system call dependencies sufficient for replay, avoiding the recording overhead of maintaining an exact execution ordering. Sync points convert asynchronous interactions that can occur at arbitrary times into synchronous events that are much easier to record and replay.
We have implemented Scribe without changing, relinking, or recompiling applications, libraries, or operating system kernels, and without any specialized hardware support such as hardware performance counters. It works on commodity Linux operating systems, and commodity multi-core and multiprocessor hardware. Our results show for the first time that an operating system mechanism can correctly and transparently record and replay multi-process and multi-threaded applications on commodity multiprocessors. Scribe recording overhead is less than 2.5% for server applications including Apache and MySQL, and less than 15% for desktop applications including Firefox, Acrobat, OpenOffice, parallel kernel compilation, and movie playback.
CWS
Authors: Casale Giuliano , Mi Ningfang , Smirni Evgenia 
Published: June 2010

We define CWS, a non-preemptive scheduling policy for workloads with correlated job sizes. CWS tackles the scheduling problem by inferring the expected sizes of upcoming jobs based on the structure of correlations and on the outcome of past scheduling decisions. Size prediction is achieved using a class of Hidden Markov Models (HMM) with continuous observation densities that describe job sizes. We show how the forward-backward algorithm of HMMs applies effectively in scheduling applications and how it can be used to derive closed-form expressions for size prediction. This is particularly simple to implement in the case of observation densities that are phase-type (PH-type) distributed, where existing fitting methods for Markovian point processes may also simplify the parameterization of the HMM workload model.
Based on the job size predictions, CWS emulates size-based policies which favor short jobs, with accuracy depending mainly on the HMM used to parametrize the scheduling algorithm. Extensive simulation and analysis illustrate that CWS is competitive with policies that assume exact information about the workload.
Deregulated Intracellular Signaling by Mutated c-CBL in Myeloid Neoplasms
Authors: Ogawa Seishi , Shih Lee-Yung , Suzuki Takahiro , Otsu Makoto , Nakauchi Hiromitsu , Koeffler H. Phillip , Sanada Masashi 
Published: June 2010

Abstractc-CBL encodes a 120-kDa protein involved in intracellular signal transduction in a wide variety of cell types. Recently, frequent mutations of c-CBL have been reported in myeloid neoplasms showing both myelodysplastic and myeloproliferative features, in which most mutations are present in a homozygous state, as a result of allelic conversion in 11q. c-CBL has ubiquitin E3 ligase activity for a wide variety of tyrosine kinases, and thereby, negatively regulates tyrosine kinase signaling. Accordingly, c-CBL seems to have tumor suppressor functions, loss of which promotes tumorigenesis. On the other hand, once mutated, it is converted to an oncogenic protein and commits to myeloid leukemogenesis through a kind of gain of function causing aberrant signal transduction. The inhibition of mutant CBL protein or signaling pathways that it activates would have a role in therapeutics of myeloid neoplasms with CBL mutations. Clin Cancer Res; 16(15); 3825–31. ©2010 AACR.
Genomic instability after allogeneic hematopoietic cell transplantation is frequent in oral mucosa, particularly in patients with a history of chronic graft-versus-host disease, and rare in nasal mucosa
Authors: Khan Faisal M. , Sy Sarah , Louie Polly , Ugarte-Torres Alejandra , Berka Noureddine , Sinclair Gary D. , Stewart Douglas A. , Russell James A. , Storek Jan 
Published: June 2010

Abstract
Genomic instability (GI) of cells may lead to their malignant transformation. Carcinoma after hematopoietic cell transplantation (HCT) frequently involves some (eg, oral) but not other (eg, nasal) epithelia. We examined GI in oral and nasal mucosal specimens from 105 subjects, including short-term (7-98 days, n = 32) and long-term (4-22 yrs, n = 25) allogeneic HCT survivors. Controls included autologous HCT survivors (n = 11), patients treated with chemotherapy without HCT (n = 9) and healthy controls (n = 27). GI was detected in 60% oral versus only 4% nasal specimens in long-term allogeneic HCT survivors (P < .001). None of the controls showed GI. In oral specimens, GI was significantly associated with history of oral chronic graft-versus-host disease (cGVHD). We conclude that GI after HCT is frequent in some (oral) but rare in other (nasal) epithelia. This may explain why some epithelia (especially those involved with cGVHD) are prone to develop cancer.
Cytogenetic and molecular diagnostic characterization combined to postconsolidation minimal residual disease assessment by flow cytometry improves risk stratification in adult acute myeloid leukemia
Authors: Buccisano Francesco , Maurillo Luca , Spagnoli Alessandra , Del Principe Maria Ilaria , Fraboni Daniela , Panetta Paola , Ottone Tiziana , Consalvo Maria Irno , Lavorgna Serena , Bulian Pietro , Ammatuna Emanuele , Angelini Daniela F. , Diamantini Adamo , Campagna Selenia , Ottaviani Licia , Sarlo Chiara , Gattei Valter , Del Poeta Giovanni , Arcese William , Amadori Sergio , Lo Coco Francesco , Venditti Adriano 
Published: June 2010

AbstractA total of 143 adult acute myeloid leukemia (AML) patients with available karyotype (K) and FLT3 gene mutational status were assessed for minimal residual disease (MRD) by flow cytometry. Twenty-two (16%) patients had favorable, 115 (80%) intermediate, and 6 (4%) poor risk K; 19 of 129 (15%) carried FLT3-ITD mutation. Considering postconsolidation MRD status, patients with good/intermediate-risk K who were MRD− had 4-year relapse-free survival (RFS) of 70% and 63%, and overall survival (OS) of 84% and 67%, respectively. Patients with good- and intermediate-risk K who were MRD+ had 4-year RFS of 15% and 17%, and OS of 38% and 23%, respectively (P < .001 for all comparisons). FLT3 wild-type patients achieving an MRD− status, had a better outcome than those who remained MRD+ (4-year RFS, 54% vs 17% P < .001; OS, 60% vs 23%, P = .002). Such an approach redefined cytogenetic/genetic categories in 2 groups: (1) low-risk, including good/intermediate K-MRD− with 4-year RFS and OS of 58% and 73%, respectively; and (2) high risk, including poor-risk K, FLT3-ITD mutated cases, good/intermediate K-MRD+ categories, with RFS and OS of 22% and 17%, respectively (P < .001 for all comparisons). In AML, the integrated evaluation of baseline prognosticators and MRD improves risk-assessment and optimizes postremission therapy.
Aurora B is dispensable for megakaryocyte polyploidization, but contributes to the endomitotic process
Authors: Lordier Larissa , Chang Yunhua , Jalil Abdelali , Aurade Frédéric , Garçon Loïc , Lécluse Yann , Larbret Frédéric , Kawashima Toshiyuki , Kitamura Toshio , Larghero Jérôme , Debili Najet , Vainchenker William 
Published: June 2010

Abstract
Polyploidization of megakaryocytes (MKs), the platelet precursors, occurs by endomitosis, a mitotic process that fails at late stages of cytokinesis. Expression and function of Aurora B kinase during endomitosis remain controversial. Here, we report that Aurora B is normally expressed during the human MK endomitotic process. Aurora B localized normally in the midzone or midbody during anaphase and telophase in low ploidy megakaryocytes and in up to 16N rare endomitotic MKs was observed. Aurora B was also functional during cytokinesis as attested by phosphorylation of both its activation site and MgcRacGAP, its main substrate. However, despite its activation, Aurora B did not prevent furrow regression. Inhibition of Aurora B by AZD1152-HQPA decreased cell cycle entry both in 2N to 4N and polyploid MKs and induced apoptosis mainly in 2N to 4N cells. In both MK classes, AZD1152-HQPA induced p53 activation and retinoblastoma hypophosphorylation. Resistance of polyploid MKs to apoptosis correlated to a high BclxL level. Aurora B inhibition did not impair MK polyploidization but profoundly modified the endomitotic process by inducing a mis-segregation of chromosomes and a mitotic failure in anaphase. This indicates that Aurora B is dispensable for MK polyploidization but is necessary to achieve a normal endomitotic process.
How I treat autoimmune hemolytic anemias in adults
Authors: Lechner Klaus , Jäger Ulrich 
Published: June 2010

Abstract
Autoimmune hemolytic anemia is a heterogeneous disease with respect to the type of the antibody involved and the absence or presence of an underlying condition. Treatment decisions should be based on careful diagnostic evaluation. Primary warm antibody autoimmune hemolytic anemias respond well to steroids, but most patients remain steroid-dependent, and many require second-line treatment. Currently, splenectomy can be regarded as the most effective and best-evaluated second-line therapy, but there are still only limited data on long-term efficacy and adverse effects. The monoclonal anti-CD20 antibody rituximab is another second-line therapy with documented short-term efficacy, but there is limited information on long-term efficacy and side effects. The efficacy of immunosuppressants is poorly evaluated. Primary cold antibody autoimmune hemolytic anemias respond well to rituximab but are resistant to steroids and splenectomy. The most common causes of secondary autoimmune hemolytic anemias are malignancies, immune diseases, or drugs. They may be treated in a way similar to primary autoimmune hemolytic anemias, by immunosuppressants or by treatment of the underlying disease.
Development of a sensitive non-radioactive protein kinase assay and its application for detecting DYRK activity in Xenopus laevis oocytes
Authors: Lilienthal Eva , Kolanowski Katharina , Becker Walter 
Published: June 2010

Abstract

Background
Although numerous non-radioactive methods are in use to measure the catalytic activity of protein kinases, most require specialized equipment and reagents and are not sufficiently sensitive for the detection of endogenous kinase activity in biological samples. Kinases of the DYRK family have important functions in developmental and pathophysiological processes in eukaryotic organisms including mammals. We aimed to develop a highly sensitive, low-tech assay suitable to determine the activity of DYRK family kinases in tissues or cells from diverse sources.

Results
Phosphorylation-site specific antibodies can be used to monitor the accumulation of the phosphorylated product in kinase assays. We present a modified configuration of an enzyme-linked immunosorbent assay (ELISA)-based kinase assay by using the phosphospecific antibody as the capture antibody. This assay format allowed the detection of small amounts of phosphopeptide in mixtures with an excess of the unphosphorylated substrate peptide (10 fmol phosphorylated peptide over a background of 50 pmol unphosphorylated peptide). Consequently, low substrate turnover rates can be determined. We applied this method to the measurement of endogenous DYRK1A activity in mouse heart tissue by immunocomplex kinase assay. Furthermore, we detected DYRK1-like kinase activity in Xenopus laevis oocytes and identified this kinase as a DYRK1 isoform distinct from the Xenopus DYRK1A ortholog.

Conclusion
We present a non-radioactive and highly sensitive method for the measurement of endogenous activities of DYRKs in biological samples. Xenopus laevis oocytes contain an active DYRK1-related protein kinase more similar to mammalian DYRK1B than DYRK1A.
Emergence and migration of trunk neural crest cells in a snake, the California Kingsnake (Lampropeltis getula californiae)
Authors: Reyes Michelle , Zandberg Katrina , Desmawati Iska , de Bellard Maria E 
Published: June 2010

Abstract

Background
The neural crest is a group of multipotent cells that emerges after an epithelial-to-mesenchymal transition from the dorsal neural tube early during development. These cells then migrate throughout the embryo, giving rise to a wide variety derivatives including the peripheral nervous system, craniofacial skeleton, pigment cells, and endocrine organs. While much is known about neural crest cells in mammals, birds, amphibians and fish, relatively little is known about their development in non-avian reptiles like snakes and lizards.

Results
In this study, we show for the first time ever trunk neural crest migration in a snake by labeling it with DiI and immunofluorescence. As in birds and mammals, we find that early migrating trunk neural crest cells use both a ventromedial pathway and an inter-somitic pathway in the snake. However, unlike birds and mammals, we also observed large numbers of late migrating neural crest cells utilizing the inter-somitic pathway in snake.

Conclusions
We found that while trunk neural crest migration in snakes is very similar to that of other amniotes, the inter-somitic pathway is used more extensively by late-migrating trunk neural crest cells in snake.
Analysis of the asymmetrically expressed Ablim1 locus reveals existence of a lateral plate Nodal-independent left sided signal and an early, left-right independent role for nodal flow
Authors: Stevens Jonathan , Ermakov Alexander , Braganca Jose , Hilton Helen , Underhill Peter , Bhattacharya Shoumo , Brown Nigel A , Norris Dominic P 
Published: June 2010

Abstract

Background
Vertebrates show clear asymmetry in left-right (L-R) patterning of their organs and associated vasculature. During mammalian development a cilia driven leftwards flow of liquid leads to the left-sided expression of Nodal, which in turn activates asymmetric expression of the transcription factor Pitx2. While Pitx2 asymmetry drives many aspects of asymmetric morphogenesis, it is clear from published data that additional asymmetrically expressed loci must exist.

Results
A L-R expression screen identified the cytoskeletally-associated gene, actin binding lim protein 1 (Ablim1), as asymmetrically expressed in both the node and left lateral plate mesoderm (LPM). LPM expression closely mirrors that of Nodal. Significantly, Ablim1 LPM asymmetry was detected in the absence of detectable Nodal. In the node, Ablim1 was initially expressed symmetrically across the entire structure, resolving to give a peri-nodal ring at the headfold stage in a flow and Pkd2-dependent manner. The peri-nodal ring of Ablim1 expression became asymmetric by the mid-headfold stage, showing stronger right than left-sided expression. Node asymmetry became more apparent as development proceeded; expression retreated in an anticlockwise direction, disappearing first from the left anterior node. Indeed, at early somite stages Ablim1 shows a unique asymmetric expression pattern, in the left lateral plate and to the right side of the node.

Conclusion
Left LPM Ablim1 is expressed in the absence of detectable LPM Nodal, clearly revealing existence of a Pitx2 and Nodal-independent left-sided signal in mammals. At the node, a previously unrecognised action of early nodal flow and Pkd2 activity, within the pit of the node, influences gene expression in a symmetric manner. Subsequent Ablim1 expression in the peri-nodal ring reveals a very early indication of L-R asymmetry. Ablim1 expression analysis at the node acts as an indicator of nodal flow. Together these results make Ablim1 a candidate for controlling aspects of L-R identity and patterning.
Reassessing the temporal evolution of orchids with new fossils and a Bayesian relaxed clock, with implications for the diversification of the rare South American genus Hoffmannseggella(Orchidaceae: Epidendroideae)
Authors: Gustafsson A Lovisa S , Verola Christiano F , Antonelli Alexandre 
Published: June 2010

Abstract

Background
The temporal origin and diversification of orchids (family Orchidaceae) has been subject to intense debate in the last decade. The description of the first reliable fossil in 2007 enabled a direct calibration of the orchid phylogeny, but little attention has been paid to the potential influence of dating methodology in obtaining reliable age estimates. Moreover, two new orchid fossils described in 2009 have not yet been incorporated in a molecular dating analysis. Here we compare the ages of major orchid clades estimated under two widely used methods, a Bayesian relaxed clock implemented in BEAST and Penalized Likelihood implemented in r8s. We then perform a new family-level analysis by integrating all 3 available fossils and using BEAST. To evaluate how the newly estimated ages may influence the evolutionary interpretation of a species-level phylogeny, we assess divergence times for the South American genus Hoffmannseggella (subfam. Epidendroideae), for which we present an almost complete phylogeny (40 out of 41 species sampled).

Results
Our results provide additional support that all extant orchids shared a most recent common ancestor in the Late Cretaceous (~77 million years ago, Ma). However, we estimate the crown age of the five orchid subfamilies to be generally (~1-8 Ma) younger than previously calculated under the Penalized Likelihood algorithm and using a single internal fossil calibration. The crown age of Hoffmannseggella is estimated here at ~11 Ma, some 3 Ma more recently than estimated under Penalized Likelihood.

Conclusions
Contrary to recent suggestions that orchid diversification began in a period of global warming, our results place the onset of diversification of the largest orchid subfamilies (Orchidoideae and Epidendroideae) in a period of global cooling subsequent to the Early Eocene Climatic Optimum. The diversification of Hoffmannseggella appears even more correlated to late Tertiary climatic fluctuations than previously suggested. With the incorporation of new fossils in the orchid phylogeny and the use of a method that is arguably more adequate given the present data, our results represent the most up-to-date estimate of divergence times in orchids.