bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Cyclic Nucleotide Monophosphate Domain ofXanthomonas campestrisGlobal Regulator Clp Defines a New Class of Cyclic Di-GMP Effectors
Authors: Tao Fei , He Ya-Wen , Wu Dong-Hui , Swarup Sanjay , Zhang Lian-Hui 
Published: December 2009

ABSTRACTThe widely conserved second messenger cyclic diguanosine monophosphate (c-di-GMP) plays a key role in quorum-sensing (QS)-dependent production of virulence factors inXanthomonas campestrispv. campestris. The detection of QS diffusible signal factor (DSF) by the sensor RpfC leads to the activation of response regulator RpfG, which activates virulence gene expression by degrading c-di-GMP. Here, we show that a global regulator in theX. campestrispv. campestris QS regulatory pathway, Clp, is a c-di-GMP effector. c-di-GMP specifically binds to Clp with high affinity and induces allosteric conformational changes that abolish the interaction between Clp and its target gene promoter. Clp is similar to the cyclic AMP (cAMP) binding proteins Crp and Vfr and contains a conserved cyclic nucleotide monophosphate (cNMP) binding domain. Using site-directed mutagenesis, we found that the cNMP binding domain of Clp contains a glutamic acid residue (E99) that is essential for c-di-GMP binding. Substituting the residue with serine (E99S) resulted in decreased sensitivity to changes in the intracellular c-di-GMP level and attenuated bacterial virulence. These data establish the direct role of Clp in the response to fluctuating c-di-GMP levels and depict a novel mechanism by which QS links the second messenger with theX. campestrispv. campestris virulence regulon.
Virulence Factors Encoded by
Legionella longbeachae
Identified on the Basis of the Genome Sequence Analysis of Clinical Isolate D-4968
Authors: Kozak Natalia A. , Buss Meghan , Lucas Claressa E. , Frace Michael , Govil Dhwani , Travis Tatiana , Olsen-Rasmussen Melissa , Benson Robert F. , Fields Barry S. 
Published: December 2009

ABSTRACT

Legionella longbeachae
causes most cases of legionellosis in Australia and may be underreported worldwide due to the lack of
L. longbeachae
-specific diagnostic tests.
L. longbeachae
displays distinctive differences in intracellular trafficking, caspase 1 activation, and infection in mouse models compared to
Legionella pneumophila
, yet these two species have indistinguishable clinical presentations in humans. Unlike other legionellae, which inhabit freshwater systems,
L. longbeachae
is found predominantly in moist soil. In this study, we sequenced and annotated the genome of an
L. longbeachae
clinical isolate from Oregon, isolate D-4968, and compared it to the previously published genomes of
L. pneumophila
. The results revealed that the D-4968 genome is larger than the
L. pneumophila
genome and has a gene order that is different from that of the
L. pneumophila
genome. Genes encoding structural components of type II, type IV Lvh, and type IV Icm/Dot secretion systems are conserved. In contrast, only 42/140 homologs of genes encoding
L. pneumophila
Icm/Dot substrates have been found in the D-4968 genome.
L. longbeachae
encodes numerous proteins with eukaryotic motifs and eukaryote-like proteins unique to this species, including 16 ankyrin repeat-containing proteins and a novel U-box protein. We predict that these proteins are secreted by the
L. longbeachae
Icm/Dot secretion system. In contrast to the
L. pneumophila
genome, the
L. longbeachae
D-4968 genome does not contain flagellar biosynthesis genes, yet it contains a chemotaxis operon. The lack of a flagellum explains the failure of
L. longbeachae
to activate caspase 1 and trigger pyroptosis in murine macrophages. These unique features of
L. longbeachae
may reflect adaptation of this species to life in soil.
Impact of Silver(I) on the Metabolism of
Shewanella oneidensis
Authors: Wang Hui , Law Nicholas , Pearson Geraldine , van Dongen Bart E. , Jarvis Roger M. , Goodacre Royston , Lloyd Jonathan R. 
Published: December 2009

ABSTRACT

Anaerobic cultures of
Shewanella oneidensis
MR-1 reduced toxic Ag(I), forming nanoparticles of elemental Ag(0), as confirmed by X-ray diffraction analyses. The addition of 1 to 50 μM Ag(I) had a limited impact on growth, while 100 μM Ag(I) reduced both the doubling time and cell yields. At this higher Ag(I) concentration transmission electron microscopy showed the accumulation of elemental silver particles within the cell, while at lower concentrations the metal was exclusively reduced and precipitated outside the cell wall. Whole organism metabolite fingerprinting, using the method of Fourier transform infrared spectroscopy analysis of cells grown in a range of silver concentrations, confirmed that there were significant physiological changes at 100 μM silver. Principal component-discriminant function analysis scores and loading plots highlighted changes in certain functional groups, notably, lipids, amides I and II, and nucleic acids, as being discriminatory. Molecular analyses confirmed a dramatic drop in cellular yields of both the phospholipid fatty acids and their precursor molecules at high concentrations of silver, suggesting that the structural integrity of the cellular membrane was compromised at high silver concentrations, which was a result of intracellular accumulation of the toxic metal.
Temporal and Spatial Regulation of the Four Transcription Start Sites of
hetR
from
Anabaena
sp. Strain PCC 7120
Authors: Rajagopalan Ramya , Callahan Sean M. 
Published: December 2009

ABSTRACT

The filamentous cyanobacterium
Anabaena
sp. strain PCC 7120 forms nitrogen-fixing heterocysts in a periodic pattern in response to combined-nitrogen limitation in the environment. The master regulator of heterocyst differentiation, HetR, is necessary for both pattern formation and commitment of approximately every 10th cell of a filament to differentiation into a heterocyst. In this study, the individual contributions of four transcriptional start points (tsps) in regulation of transcription of
hetR
were assessed, and the effects of the regulatory genes
patS
,
hetN
, and
patA
on transcription from the tsps were determined. The tsp located at nucleotide −271 relative to the translational start site (−271 tsp) was the most tightly regulated tsp, and fluorescence from a −271 tsp-green fluorescent protein (GFP) reporter fusion was observed initially in groups of two cells and later in single cells arranged in a spatial pattern that mimicked the pattern of heterocysts that emerged. Conversely, the fluorescence from the −184 and −728/−696 tsp-GFP reporter fusions was uniform throughout filaments. Transcription from the −271 tsp was severely downregulated in a strain in which the
patA
gene, which encodes a positive regulator of differentiation, was deleted, and it was not detectable in strains overexpressing the genes encoding the negative regulators of differentiation,
patS
and
hetN
. In strains lacking the −271 tsp of
hetR
, pattern formation, the timing of commitment to differentiation, and the number of cells that differentiated into heterocysts were affected. Taken together, these results demonstrate the role of regulation of the −271 tsp of
hetR
in the genetic network that governs heterocyst pattern formation and differentiation.
Extracytoplasmic PAS-Like Domains Are Common in Signal Transduction Proteins
Authors: Chang Changsoo , Tesar Christine , Gu Minyi , Babnigg Gyorgy , Joachimiak Andrzej , Pokkuluri P. Raj , Szurmant Hendrik , Schiffer Marianne 
Published: December 2009

ABSTRACT

We present the crystal structure of the extracytoplasmic domain of the
Bacillus subtilis
PhoR sensor histidine kinase, part of a two-component system involved in adaptation to low environmental phosphate concentrations. In addition to the PhoR structure, we predict that the majority of the extracytoplasmic domains of
B. subtilis
sensor kinases will adopt a fold similar to the ubiquitous PAS domain.
Steady and non-steady state kinetics describe polychlorinated biphenyl bioaccumulation in natural populations of bluegill (Lepomis macrochirus) and cisco (Coregonus artedi)
Authors: Burtnyk Michael D. , Paterson Gordon , Drouillard Kenneth G. , Haffner G. Douglas 
Published: December 2009

This study investigated polychlorinated biphenyl (PCB) bioaccumulation patterns across age classes of bluegill ( Lepomis macrochirus ) and cisco ( Coregonus artedi ) collected from Sharbot Lake, Ontario. For bluegill, lipid normalized concentrations of PCB congeners of log Kow < 6.8 did not demonstrate any significant increases across individuals 2–5 years of age. In similarly aged cisco, however, significant age-related increases in lipid normalized PCB concentrations were observed for the majority of these congeners. For PCBs of log Kow > 6.8, these congeners demonstrated significant and similar age-related fugacity increases in both species. These patterns indicated that the bioaccumulation of less hydrophobic PCB congeners in bluegill suggest quicker growth kinetics and demonstrate the potential of this species to achieve steady state within their lifetime. In contrast, PCB bioaccumulation patterns in cisco demonstrated that biomagnification and non-steady state kinetics better reflect the capacity of this species to bioaccumulate PCBs. These results demonstrated that for pollutants of log Kow < 6.8, growth dilution and age-specific metabolic rates are critical for understanding their bioaccumulation by freshwater fish. However, for increasingly hydrophobic pollutants, their bioaccumulation reflects the biology and ecology of these species in their respective warm- and cold-water habitats.
Impact of temperature on the linear viscoelastic region of wood
Authors: Jiang Jiali , Lu Jianxiong 
Published: December 2009

The impact of temperature on the linear viscoelastic region, which is characterized by critical strain, of Chinese fir ( Cunninghamia lanceolata (Lamb.) Hook.) was investigated at various temperatures between –100 and 220 °C for specimens with a moisture content of approximately 0.6%. The effect of oscillation frequency on the linear viscoelastic region under various constant temperatures was also examined. The results indicated that critical strain generally decreased with increasing temperature except at –80, –20, 40, 120, and 220 °C. These five exceptions were attributed to the occurrence of relaxation processes. With an increase in testing frequency from 1 to 20 Hz, the critical strain decreased slightly at all temperatures. It is suggested that the stored elastic energy and yield stress, which were obtained at critical strain, could be indicators to predict wood mechanical performance.
Decomposition of pure and mixed foliage litter in a young lodgepole pine – Sitka alder stand in the central interior of British Columbia
Authors: Sanborn P.T. , Brockley R.P. 
Published: December 2009

A 7-year litterbag experiment examined mass loss dynamics of Sitka alder ( Alnus viridis (Chaix) DC. subsp. sinuata (Regel) A. Löve & D. Löve) and lodgepole pine ( Pinus contorta Dougl. ex Loud. var. latifolia Engelm. ex S. Watson) foliage litter in a young stand dominated by these species in the Sub-Boreal Spruce biogeoclimatic zone of central British Columbia. Although mass loss was initially faster for alder litter, the amounts of mass remaining for alder, pine, and mixed pine–alder (50:50 by mass) litter began to converge after 2 years. Mass loss by the mixed litter differed significantly from that predicted from the behaviour of its pure components, but the mechanisms responsible could not be determined from this experiment. Limit values for the projected maximum extent of mass loss ranged from 63.5% (alder) to 76.9% (pine), with the latter value considerably below estimates reported for lodgepole pine in Scandinavia. Despite these differing limit values, forest floor mass measurements prior to the experiment did not show significantly higher organic matter accumulations under long-established alder clumps on this site.
Investigation of Variants Identified in Caucasian Genome-Wide Association Studies for Plasma High-Density Lipoprotein Cholesterol and Triglycerides Levels in Mexican Dyslipidemic Study Samples
Authors: Weissglas-Volkov Daphna , Aguilar-Salinas Carlos A. , Sinsheimer Janet S. , Riba Laura , Huertas-Vazquez Adriana , Ordoñez-Sánchez Maria L. , Rodriguez-Guillen Rosario , Cantor Rita M. , Tusie-Luna Teresa , Pajukanta Päivi 
Published: December 2009

Background—Although epidemiological studies have demonstrated an increased predisposition to low high-density lipoprotein cholesterol and high triglyceride levels in the Mexican population, Mexicans have not been included in any of the previously reported genome-wide association studies for lipids.Methods and Results—We investigated 6 single-nucleotide polymorphisms associated with triglycerides, 7 with high-density lipoprotein cholesterol, and 1 with both triglycerides and high-density lipoprotein cholesterol in recent Caucasian genome-wide association studies in Mexican familial combined hyperlipidemia families and hypertriglyceridemia case-control study samples. These variants were within or near the genesABCA1,ANGPTL3,APOA5,APOB,CETP,GALNT2,GCKR,LCAT,LIPC,LPL (2),MMAB-MVK,TRIB1, andXKR6-AMAC1L2. We performed a combined analysis of the family-based and case-control studies (n=2298) using theZmethod to combine statistics. Ten of the single-nucleotide polymorphisms were nominally significant and 5 were significant after Bonferroni correction (P=2.20�10−3to 2.6�10−11) for the number of tests performed (APOA5, CETP, GCKR, and GALNT2). Interestingly, our strongest signal was obtained for triglycerides with the minor allele of rs964184 (P=2.6�10−11) in the APOA1/C3/A4/A5 gene cluster region that is significantly more common in Mexicans (27%) than in whites (12%).Conclusions—It is important to confirm whether known loci have a consistent effect across ethnic groups. We show replication of 5 Caucasian genome-wide association studies lipid associations in Mexicans. The remaining loci will require a comprehensive investigation to exclude or verify their significance in Mexicans. We also demonstrate that rs964184 has a large effect (odds ratio, 1.74) and is more frequent in the Mexican population, and thus it may contribute to the high predisposition to dyslipidemias in Mexicans.
ROCK1 functions as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability
Authors: Vemula Sasidhar , Shi Jianjian , Hanneman Philip , Wei Lei , Kapur Reuben 
Published: December 2009

AbstractRho kinases belong to a family of serine/threonine kinases whose role in recruitment and migration of inflammatory cells is poorly understood. We show that deficiency of ROCK1 results in increased recruitment and migration of macrophages and neutrophils in vitro and in vivo. Enhanced migration resulting from ROCK1 deficiency is observed despite normal expression of ROCK2 and a significant reduction in overall ROCK activity. ROCK1 directly binds PTEN in response to receptor activation and is essential for PTEN phosphorylation and stability. In the absence of ROCK1, PTEN phosphorylation, stability, and its activity are significantly impaired. Consequently, increased activation of downstream targets of PTEN, including PIP3, AKT, GSK-3β, and cyclin D1, is observed. Our results reveal ROCK1 as a physiologic regulator of PTEN whose function is to repress excessive recruitment of macrophages and neutrophils during acute inflammation.
Targeting distinct tumor-infiltrating myeloid cells by inhibiting CSF-1 receptor: combating tumor evasion of antiangiogenic therapy
Authors: Priceman Saul J. , Sung James L. , Shaposhnik Zory , Burton Jeremy B. , Torres-Collado Antoni X. , Moughon Diana L. , Johnson Mai , Lusis Aldons J. , Cohen Donald A. , Iruela-Arispe M. Luisa , Wu Lily 
Published: December 2009

Abstract
Tumor-infiltrating myeloid cells (TIMs) support tumor growth by promoting angiogenesis and suppressing antitumor immune responses. CSF-1 receptor (CSF1R) signaling is important for the recruitment of CD11b+F4/80+ tumor-associated macrophages (TAMs) and contributes to myeloid cell-mediated angiogenesis. However, the impact of the CSF1R signaling pathway on other TIM subsets, including CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs), is unknown. Tumor-infiltrating MDSCs have also been shown to contribute to tumor angiogenesis and have recently been implicated in tumor resistance to antiangiogenic therapy, yet their precise involvement in these processes is not well understood. Here, we use the selective pharmacologic inhibitor of CSF1R signaling, GW2580, to demonstrate that CSF-1 regulates the tumor recruitment of CD11b+Gr-1loLy6Chi mononuclear MDSCs. Targeting these TIM subsets inhibits tumor angiogenesis associated with reduced expression of proangiogenic and immunosuppressive genes. Combination therapy using GW2580 with an anti–VEGFR-2 antibody synergistically suppresses tumor growth and severely impairs tumor angiogenesis along with reverting at least one TIM-mediated antiangiogenic compensatory mechanism involving MMP-9. These data highlight the importance of CSF1R signaling in the recruitment and function of distinct TIM subsets, including MDSCs, and validate the benefits of targeting CSF1R signaling in combination with antiangiogenic drugs for the treatment of solid cancers.
Lenalidomide plus dexamethasone versus thalidomide plus dexamethasone in newly diagnosed multiple myeloma: a comparative analysis of 411 patients
Authors: Gay Francesca , Hayman Suzanne R. , Lacy Martha Q. , Buadi Francis , Gertz Morie A. , Kumar Shaji , Dispenzieri Angela , Mikhael Joseph R. , Bergsagel P. Leif , Dingli David , Reeder Craig B. , Lust John A. , Russell Stephen J. , Roy Vivek , Zeldenrust Steven R. , Witzig Thomas E. , Fonseca Rafael , Kyle Robert A. , Greipp Philip R. , Stewart A. Keith , Rajkumar S. Vincent 
Published: December 2009

AbstractThe objective of this case-control study was to compare the efficacy and toxicity of lenalidomide plus dexamethasone (len/dex) versus thalidomide plus dexamethasone (thal/dex) as initial therapy for newly diagnosed myeloma. We retrospectively studied 411 newly diagnosed patients treated with len/dex (228) or thal/dex (183) at the Mayo Clinic. The differences were similar in a matched-pair analysis that adjusted for age, sex, transplantation status, and dexamethasone dose. The proportions of patients achieving at least a partial response to len/dex and thal/dex were 80.3% versus 61.2%, respectively (P < .001); very good partial response rates were 34.2% and 12.0%, respectively (P < .001). Patients receiving len/dex had longer time to progression (median, 27.4 vs 17.2 months; P = .019), progression-free survival (median, 26.7 vs 17.1 months; P = .036), and overall survival (median not reached vs 57.2 months; P = .018). A similar proportion of patients in the 2 groups experienced at least one grade 3 or 4 adverse event (57.5% vs 54.6%, P = .568). Main grade 3 or 4 toxicities of len/dex were hematologic, mainly neutropenia (14.6% vs 0.6%, P < .001); the most common toxicities in thal/dex were venous thromboembolism (15.3% vs 9.2%, P = .058) and peripheral neuropathy (10.4% vs 0.9%, P < .001). Len/dex appears well-tolerated and more effective than thal/dex. Randomized trials are needed to confirm these results.
Association of HLA-A, B, DRB1 alleles and haplotypes with HIV-1 infection in Chongqing, China
Authors: Huang Xia , Ling Hua , Mao Wei , Ding Xianbin , Zhou Quanhua , Han Mei , Wang Fang , Cheng Lei , Xiong Hongyan 
Published: December 2009

Abstract

Background
The human immunodeficiency virus type 1(HIV-1) epidemic in Chongqing, China, is increasing rapidly with the dominant subtype of CRF07_BC over the past 3 years. Since human leukocyte antigen (HLA) polymorphisms have shown strong association with susceptibility/resistance to HIV-1 infection from individuals with different ethnic backgrounds, a recent investigation on frequencies of HLA class I and class II alleles in a Chinese cohort also indicated that similar correlation existed in HIV infected individuals from several provinces in China, however, such information is unavailable in Chongqing, southwest China.

Methods
In this population-based study, we performed polymerase chain reaction analysis with sequence-specific oligonucleotide probes (PCR-SSOP) for intermediate-low-resolution HLA typing in a cohort of 549 HIV-1 infected individuals, another 2475 healthy subjects from the Han nationality in Chongqing, China, were selected as population control. We compared frequencies of HLA-A, B, DRB1 alleles, haplotypes and genotypes between the two groups, and analyzed their association with HIV-1 susceptibility or resistance.

Results
The genetic profile of HLA (A, B, DRB1) alleles of HIV-1 infected individuals from Chongqing Han of China was obtained. Several alleles of HLA-B such as B*46 (P = 0.001, OR = 1.38, 95%CI = 1.13-1.68), B*1501G(B62) (P = 0.013, OR = 1.42, 95%CI = 1.08-1.88), B*67 (P = 0.022, OR = 2.76, 95%CI = 1.16-6.57), B*37 (P = 0.014, OR = 1.93, 95%CI = 1.14-3.28) and B*52 (P = 0.038, OR = 1.64, 95%CI = 1.03-2.61) were observed to have association with susceptibility to HIV-1 infection in this population. In addition, the haplotype analysis revealed that A*11-B*46, A*24-B*54 and A*01-B*37 for 2-locus, and A*11-B*46-DRB1*09, A*02-B*46-DRB1*08, A*11-B*4001G-DRB1*15, A*02-B*4001G-DRB1*04, A*11-B*46-DRB1*08 and A*02-B*4001G-DRB1*12 for 3-locus had significantly overrepresented in HIV-1 infected individuals, whereas A*11-B*1502G, A*11-B*1502G-DRB1*12 and A*33-B*58-DRB1*13 were underrepresented. However, the low-resolution homozygosity of HLA-A, B, DRB1 loci and HLA-Bw4/Bw6 genotypes did not differ significantly between the two groups.

Conclusion
These results may contribute to the database of HLA profiles in HIV-1 infected Chinese population, consequently, the association of certain HLA alleles with susceptibility or resistance to HIV-1 infection would provide with clues in choosing proper preventive strategies against HIV-1 infection and developing effective HIV-1 vaccines in Chinese population, especially for those in southwest China.
Association of measures of fetal and childhood growth with
non-clinical psychotic symptoms in 12-year-olds: the ALSPAC
cohort
Authors: Thomas K. , Harrison G. , Zammit S. , Lewis G. , Horwood J. , Heron J. , Hollis C. , Wolke D. , Thompson A. , Gunnell D. 
Published: December 2009

BackgroundPrevious studies have suggested that impaired fetal and childhood growth
are associated with an increased risk of schizophrenia, but the
association of pre-adult growth with non-clinical psychotic symptoms
(psychosis-like symptoms) in children is not known.AimsTo explore the associations of body size at birth and age 7.5 years with
childhood psychosis-like symptoms.MethodProspective cohort of children followed up from birth to age 12: the
ALSPAC cohort.ResultsData on 6000 singleton infants born after 37 weeks of gestation. A one
standard deviation increase in birth weight was associated with an 18%
reduction in the risk of definite psychosis-like symptoms after adjusting
for age and gestation (Odds ratio (OR) = 0.82, 95% CI = 0.73–0.92,
P = 0.001). This association was partly confounded by
maternal anthropometry, smoking during pregnancy, socioeconomic status
and IQ. A similar association was seen for birth length and
psychosis-like symptoms, which disappeared after controlling for birth
weight. There was little evidence for an association of 7-year height or
adiposity with psychosis-like symptoms.ConclusionsMeasures of impaired fetal, but not childhood, growth are associated with
an increased risk of psychosis-like symptoms in 12-year-olds.
Mass Spectrometric Approach Delineating Degradation Mechanism of Synthethic Polymers by Benzoylferrocene
Authors: Kagawa Shuji , Kawasaki Hideya , Arakawa Ryuichi 
Published: December 2009

Abstract
The degradation effects of benzoylferrocene (BF) on poly(ethylene glycol) (PEG) and poly(methyl methacrylate) (PMMA) were investigated using MALDI-MS. It is supposed that the release of free radicals in solution by BF plays a key role in the decomposition of PEG and PMMA. MALDI-MS combined with examination of the degradation by BF could be applied to the analysis of synthetic polymer structures containing the PEG and PMMA chain.