bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type III secretion‐dependent host defence elicitation and type III secretion‐independent growth within leaves by Xanthomonas campestris pv. campestris
Authors: SUN WENXIAN , LIU LIJUAN , BENT ANDREW F. 
Published: March 2011

SUMMARYIn many plant–bacterial interactions, loss of the type III secretion system (T3SS) severely reduces bacterial growth, symptom causation and suppression of defences in host plants. In the present study of Xanthomonas campestris pv. campestris (Xcc), Xcc strain B305 grew better than strain B186 in Arabidopsis thaliana after hydathode inoculation, and B305 strains mutated to the loss of T3SS (ΔhrcC and/or ΔhrpE; also ΔhrcCΔflgBC) grew similarly to wild‐type B305 in Arabidopsis leaves. Unlike Xcc strain B186, wild‐type B305 was relatively inefficient in secreting the exogenous T3S effector AvrBsT, but ΔhrcC and/or ΔhrpE attenuated the disease symptoms caused by Xcc B305, showing that the partially compromised T3SS of this strain still promotes necrotic leaf symptoms. In contrast with the T3SS‐dependent defence suppression that has been observed for some other plant pathogenic bacteria, the Xcc B186 and B305 wild‐type strains (which are virulent on Arabidopsis) caused greater elicitation of host PR‐1 and PR‐5 expression and callose deposition in comparison with their respective T3SS mutants. A defence‐suppressing/virulence‐enhancing activity of the Xcc T3SS effector suite was detectable when co‐inoculation with wild‐type Xcc B186 increased the growth of ΔhrcC Xcc, but this activity did not prevent the above defence elicitation. Experiments using T3SS mutants and Arabidopsis fls2 mutants suggested that FLS2 does not play a prominent role in restriction of the examined Xcc strains. However, ectopic overexpression of the Pseudomonas syringae effector AvrPto promoted in planta growth of wild‐type and ΔhrcC Xcc. In summary, the T3SS components or effector suite from virulent Xcc strains elicit some host defence responses, but suppress other defences and stimulate more severe disease symptoms, AvrPto‐disruptable elements other than FLS2 apparently contribute to the host restriction of Xcc, and in some virulent Xcc strains the T3SS is not absolutely required for wild‐type levels of bacterial growth within the plant.
Negative regulation of defence signalling pathways by the EDR1 protein kinase
Authors: CHRISTIANSEN KATY M. , GU YANGNAN , RODIBAUGH NATALIE , INNES ROGER W. 
Published: March 2011

SUMMARYThe enhanced disease resistance 1 (edr1) mutant of Arabidopsis confers enhanced resistance to bacterial and fungal pathogens. To better understand how edr1‐mediated resistance occurs, we performed transcriptome analyses on wild‐type and edr1 plants inoculated with the fungal pathogen Golovinomyces cichoracearum (powdery mildew). The expression of many known and putative defence‐associated genes was more rapidly induced, and to higher levels, in edr1 plants relative to the wild‐type. Many of the genes with elevated expression encoded WRKY transcription factors and there was enrichment for their binding sites in promoters of the genes upregulated in edr1. Confocal microscopy of transiently expressed EDR1 protein showed that a significant fraction of EDR1 was localized to the nucleus, suggesting that EDR1 could potentially interact with transcription factors in the nucleus. Analysis of gene ontology annotations revealed that genes associated with the endomembrane system, defence, reactive oxygen species (ROS) production and protein kinases were induced early in the edr1 mutant, and that elevated expression of the endomembrane system, defence and ROS‐related genes was maintained for at least 4 days after infection.
The pharmacokinetics of PF‐734200, a DPP‐IV inhibitor, in subjects with renal insufficiency
Authors: Dai Haiqing , Johnson Susan L. , Terra Steven G. , Marbury Thomas C. , Smith William B. , Alcorn Harry , Boyd Rebecca A. , Wang Rong , Nguyen Tu T. 
Published: March 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Data demonstrating the pharmacokinetics (PK), efficacy and tolerability of PF‐734200, a potent DPP‐IV inhibitor in subjects with normal renal function, have been published or presented. WHAT THIS STUDY ADDS • This study provides better data on the PK of PF‐734200 in subjects with varying degrees of renal insufficiency and in subjects with end‐stage renal disease undergoing haemodialysis. In assessing the effects of renal impairment on the PK of PF‐734200, this study provides evidence for potential dose adjustment of PF‐734200 in patients with certain categories of renal impairment.AIMS PF‐734200 is a potent, selective inhibitor of DPP‐IV. This two‐part study evaluated the pharmacokinetics (PK) of oral 20 mg PF‐734200 in subjects with varying degrees of renal insufficiency or with end‐stage renal disease (ESRD) requiring chronic haemodialysis (HD). The study also assessed the HD clearance of PF‐734200 in ESRD.METHODS Part 1 included subjects with normal renal function or renal insufficiency but not on HD. Subjects received a single dose of 20 mg PF‐734200 while fasting and serum and urine samples were collected. In part 2, period 1, 1 h after HD, a single 20‐mg dose was given to subjects with ESRD and serum samples were collected. After a 7‐day washout, subjects received another dose followed by collection of serum samples (period 2), during which HD was initiated 4 h after dosing. Dialysate samples were collected to quantify amount of drug removed, from which HD clearance was calculated. The fraction of drug dialysed was calculated using an AUC‐based method.RESULTS Systemic exposures of PF‐734200 increased approximately 1.5‐, 2.2‐, 2.1‐ and 2.8‐fold in subjects with mild, moderate, or severe renal insufficiency or ESRD, respectively, compared with subjects with normal renal function. The terminal half‐life increased from 16.2 h in subjects with normal renal function to 36.6 h in subjects with ESRD. Approximately, 29% of PF‐734200 in the body after a single‐dose administration was dialysed by 4 h HD.CONCLUSIONS Systemic exposure of PF‐734200 increases with decreasing renal function. The effect of HD on drug removal is modest.
CD16+ monocytes in breast cancer patients: expanded by monocyte chemoattractant protein-1 and may be useful for early diagnosis
Authors: Feng A-L , Zhu J-K , Sun J-T , Yang M-X , Neckenig M R , Wang X-W , Shao Q-Q , Song B-F , Yang Q-F , Kong B-H , Qu X 
Published: March 2011

Summary
Human peripheral blood monocytes are a heterogeneous population, including CD14+CD16- ‘classical’ monocytes and CD14+CD16+‘proinflammatory’ monocytes. CD16+ monocytes are expanded in various inflammatory conditions. However, little is known about the CD14+CD16+ monocytes in patients with breast cancer. We detected CD14+CD16+ monocytes in 96 patients with breast cancer and 54 control subjects using flow cytometry. Receiver-operating characteristic (ROC) curve analysis was used to determine the feasibility of CD14+CD16+ monocytes as an indicator for diagnosis of breast cancer. We found that the frequency of CD14+CD16+ monocytes showed a significantly greater increase in breast cancer patients than in controls (16·96% versus 10·84%, P &lt; 0·0001). The area under the ROC curve for CD14+CD16+ monocytes was 0·805 [95% confidence interval (95% CI): 0·714–0·877, P = 0·0001]. Furthermore, the levels of CD16+ monocytes were significantly negatively associated with the tumour size and pathological staging. In vitro, we showed that CD14+CD16+ monocytes were expanded significantly when the purified CD14+ monocytes were exposed to Michigan Cancer Foundation (MCF)-7 cells-conditioned medium (MCF-CM) or, separately, to monocyte chemotactic protein 1 (MCP-1). Neutralizing antibodies against MCP-1 inhibited the expansion of CD14+CD16+ monocytes by MCF-CM. Collectively, our findings indicated that MCP-1 can expand CD14+CD16+ monocytes in patients with breast cancer. Furthermore, the CD14+CD16+ monocyte may be a useful indicator in early diagnosis of breast cancer.
Stimulation of a shorter duration in the state of anergy by an invariant natural killer T cell agonist enhances its efficiency of protection from type 1 diabetes
Authors: Tohn R , Blumenfeld H , Haeryfar S M M , Veerapen N , Besra G S , Porcelli S A , Delovitch T L 
Published: March 2011

SummaryWe have reported previously that treatment of non-obese diabetic (NOD) mice with the invariant natural killer T (iNK T) cell agonist α-galactosylceramide C26:0 (α-GalCer) or its T helper type 2 (Th2)-biasing derivative α-GalCer C20:2 (C20:2) protects against type 1 diabetes (T1D), with C20:2 yielding greater protection. After an initial response to α-GalCer, iNK T cells become anergic upon restimulation. While such anergic iNK T cells can induce tolerogenic dendritic cells (DCs) that mediate protection from T1D, chronic administration of α-GalCer also results in long-lasting anergy accompanied by significantly reduced iNK T cell frequencies, which raises concerns about its long-term therapeutic use. In this study, our objective was to understand more clearly the roles of anergy and induction of tolerogenic DCs in iNK T cell-mediated protection from T1D and to circumvent potential complications associated with α-GalCer. We demonstrate that NOD iNK T cells activated during multi-dose (MD) treatment in vivo with C20:2 enter into and exit from anergy more rapidly than after activation by α-GalCer. Importantly, this shorter duration of iNK T cells in the anergic state promotes the more rapid induction of tolerogenic DCs and reduced iNK T cell death, and enables C20:2 stimulated iNK T cells to elicit enhanced protection from T1D. Our findings further that suggest C20:2 is a more effective therapeutic drug than α-GalCer for protection from T1D. Moreover, the characteristics of C20:2 provide a basis of selection of next-generation iNK T cell agonists for the prevention of T1D.
Uncertainty analysis for the integration of seismic and controlled source electro‐magnetic data
Authors: Kwon Myoung Jae , Snieder Roel 
Published: March 2011

ABSTRACTWe study the appraisal problem for the joint inversion of seismic and controlled source electro‐magnetic (CSEM) data and utilize rock‐physics models to integrate these two disparate data sets. The appraisal problem is solved by adopting a Bayesian model and we incorporate four representative sources of uncertainty. These are uncertainties in 1) seismic wave velocity, 2) electric conductivity, 3) seismic data and 4) CSEM data. The uncertainties in porosity and water saturation are quantified by a posterior random sampling in the model space of porosity and water saturation in a marine one‐dimensional structure. We study the relative contributions from the four individual sources of uncertainty by performing several statistical experiments. The uncertainties in the seismic wave velocity and electric conductivity play a more significant role on the variation of posterior uncertainty than do the seismic and CSEM data noise. The numerical simulations also show that the uncertainty in porosity is most affected by the uncertainty in the seismic wave velocity and that the uncertainty in water saturation is most influenced by the uncertainty in electric conductivity. The framework of the uncertainty analysis presented in this study can be utilized to effectively reduce the uncertainty of the porosity and water saturation derived from the integration of seismic and CSEM data.
Allogeneic apoptotic thymocyte‐stimulated dendritic cells expand functional regulatory T cells
Authors: da Costa Thaís Boccia , Sardinha Luiz R. , Larocca Rafael , Peron Jean P. S. , Rizzo Luiz V. 
Published: March 2011

SummaryDendritic cells (DCs) play an important role in the clearance of apoptotic cells. The removal of apoptotic cells leads to peripheral tolerance, although their role is still not clear. We show that the uptake of apoptotic thymocytes by DCs converts these cells into tolerogenic DCs resistant to maturation by lipopolysaccharide, modulating the production of interleukin‐12 and up‐regulating the expression of transforming growth factor‐β1 latency associated peptide. We also observed that DCs pulsed with apoptotic cells in the allogeneic context were more efficient in the expansion of regulatory T cells (Tregs), and that this expansion requires contact between DCs and the T cell. The Tregs sorted from in vitro culture suppressed the proliferation of splenocytes in vitro in a specific and non‐specific manner. In the in vivo model, the transfer of CD4+ CD25− cells to Nude mice induced autoimmunity, with cell infiltrate found in the stomach, colon, liver and kidneys. The co‐transfer of CD4+ CD25− and CD4+ CD25+ prevented the presence of cell infiltrates in several organs and increased the total cell count in lymph nodes. Our data indicate that apoptotic cells have an important role in peripheral tolerance via induction of tolerogenic DCs and CD4+ CD25+ Foxp3+ cells that present regulatory functions.
The quorum‐hindered transcription factor YenR of Yersinia enterocolitica inhibits pheromone production and promotes motility via a small non‐coding RNA
Authors: Tsai Ching‐Sung , Winans Stephen C. 
Published: March 2011

SummaryThe YenR and YenI proteins of Yersinia enterocolitica resemble the quorum sensing proteins LuxR and LuxI of Vibrio fischeri. Apo‐YenR activated a gene, designated yenS, that lies adjacent to and divergent from yenR. YenR‐dependent expression of yenS was inhibited by endogenous or exogenous 3‐oxohexanoylhomoserine lactone (OHHL) a pheromone made by YenI. Purified apo‐YenR bound non‐cooperatively to two 20‐nucleotide sites that lie upstream of yenS. Binding occurred in the absence of (OHHL), and YenR was largely released from the DNA by this pheromone. yenS encoded two non‐translated RNAs 169 and 105 nucleotides long that share the same 5′ end but have different 3′ ends. One or both RNAs inhibited the translation and accumulation of the yenI mRNA by binding to a region that overlaps the YenI start codon. A mutation in yenI strongly stimulated swarming motility on the surface of semi‐solid agar, while exogenous OHHL completely suppressed this phenotype. Hypermotility in yenI mutants was also suppressed by mutations in yenR or yenS, suggesting that YenS plays a direct, stimulatory role in swarming motility.
Many ways to build an actin filament
Authors: Popp David , Robinson Robert C. 
Published: March 2011

SummaryCells rely on extensive networks of protein fibres to help maintain their proper form and function. For species ranging from bacteria to humans, this ‘cytoskeleton’ is integrally involved in diverse processes including movement, DNA segregation, cell division and transport of molecular cargoes. The most abundant cytoskeletal filament‐forming protein, F‐actin, is remarkably well conserved across eukaryotic species. From yeast to human – an evolutionary distance of over one billion years – only about 10% of residues in actin have changed and the filament structure has been highly conserved. Surprisingly, recent structural data show this to be not the case for filamentous bacterial actins, which exhibit highly divergent helical symmetries in conjunction with structural plasticity or polymorphism, and dynamic properties that may make them uniquely suited for the specific cellular processes in which they participate. Bacterial actin filaments often organize themselves into complex structures within the prokaryotic cell, driven by molecular crowding and cation association, to form bundles (ParM) or interwoven sheets (MreB). The formation of supramolecular structures is essential for bacterial cytoskeleton function. We discuss the underlying physical principles that lead to complex structure formation and the implications these have on the physiological functions of cytoskeletal proteins.
Unravelling the regulatory twist – regulation of CO2 fixation in Rhodopseudomonas palustris CGA010 mediated by atypical response regulator(s)†
Authors: Joshi Gauri S. , Bobst Cedric E. , Tabita F. Robert 
Published: March 2011

SummaryIn Rhodopseudomonas palustris CGA010, the LysR type regulator, CbbR, specifically controls transcription of the cbbLS genes encoding form I RubisCO. Previous genetic and physiological studies had indicated that a unique two‐component (CbbRRS) system influences CbbR‐mediated cbbLS transcription under conditions where CO2 is the sole carbon source. In this study, we have established direct protein–protein interactions between the response regulators of the CbbRRS system and CbbR, using a variety of techniques. The bacterial two‐hybrid system established a specific interaction between CbbR and CbbRR1 (response regulator 1 of the CbbRRS system), confirmed in vitro by chemical cross‐linking. In addition, both response regulators (CbbRR1 and CbbRR2) played distinct roles in influencing the CbbR–cbbLS promoter interactions in gel mobility shift assays. CbbRR1 increased the binding affinity of CbbR at the cbbI promoter three‐ to fivefold while CbbRR2 appeared to stabilize CbbR binding. Specific interactions were further supported by surface plasmon resonance (SPR) analyses. In total, the results suggested that both response regulators, with no discernible DNA‐binding domains, must interact with CbbR to influence cbbLS expression. Thus the CbbRRS system provides an additional level of transcriptional control beyond CbbR alone, and appears to be significant for potentially fine‐tuning cbbLS expression in Rps. palustris.
The roles of PCNA SUMOylation, Mms2‐Ubc13 and Rad5 in translesion DNA synthesis in Saccharomyces cerevisiae
Authors: Halas Agnieszka , Podlaska Agnieszka , Derkacz Joanna , McIntyre Justyna , Skoneczna Adrianna , Sledziewska‐Gojska Ewa 
Published: March 2011

SummaryMms2, in concert with Ubc13 and Rad5, is responsible for polyubiquitination of replication processivity factor PCNA. This modification activates recombination‐like DNA damage‐avoidance mechanisms, which function in an error‐free manner. Cells deprived of Mms2, Ubc13 or Rad5 exhibit mutator phenotypes as a result of the channelling of premutational DNA lesions to often error‐prone translesion DNA synthesis (TLS). Here we show that Siz1‐mediated PCNA SUMOylation is required for the stimulation of this TLS, despite the presence of PCNA monoubiquitination. The stimulation of spontaneous mutagenesis by Siz1 in cells carrying rad5 and/or mms2 mutations is connected with the known role of PCNA SUMOylation in the inhibition of Rad52‐mediated recombination. However, following UV irradiation, Siz1 is engaged in additional, as yet undefined, mechanisms controlling genetic stability at the replication fork. We also demonstrate that in the absence of PCNA SUMOylation, Mms2‐Ubc13 and Rad5 may, independently of each other, function in the stimulation of TLS. Based on this finding and on an analysis of the epistatic relationships between SIZ1, MMS2 and RAD5, with respect to UV sensitivity, we conclude that PCNA SUMOylation is responsible for the functional differences between the Mms2 and Rad5 homologues of Saccharomyces cerevisiae and Schizosaccharomyces pombe.
BAG3‐related myofibrillar myopathy in a Chinese family
Authors: Lee HC , Cherk SW , Chan SK , Wong S , Tong TW , Ho WS , Chan AY , Lee KC , Mak CM 
Published: March 2011

Lee HC, Cherk SW, Chan SK, Wong S, Tong TW, Ho WS, Chan AY, Lee KC, Mak CM. BAG3‐related myofibrillar myopathy in a Chinese family.In contrast to the usual slow disease progression in myofibrillar myopathies, patients with Bag3opathy often have a rapidly progressive and more severe phenotype with a worse prognosis. We describe a Chinese patient, born to non‐consanguineous parents, who first presented at age 6 with clumsy walking and difficult climbing staircase. With a history of restrictive lung disease previously diagnosed as asthma, she progressed rapidly with proximal myopathy, rigid spine and bilateral tightening of the Achilles tendons requiring surgical elongation. Hypertrophic cardiomyopathy with restrictive physiology was shown by echocardiogram. Moreover, prolonged QT interval was also noted in the patient. Family history was unremarkable yet her father was incidentally found to have prolonged QT interval. Mutation analysis with genomic DNA of the proband showed heterozygous de novo known mutation c.626C>T (p.Pro209Leu) and a germline variation c.772C>T (p.Arg258Trp) in BAG3. Her father was found to be a carrier of c.772C>T. Muscle biopsy findings were suggestive of myofibrillar myopathy on light microscopy and ultrastructural studies. To our knowledge, this is the first Chinese case of Bag3opathy so far reported.
Growth of a nation part I: impact of organ donor obesity on whole‐organ pancreas transplantation
Authors: Fridell Jonathan A. , Mangus Richard S. , Taber Tim E. , Goble Michelle L. , Milgrom Martin L. , Good Jason , Vetor Ryan , Powelson John A. 
Published: March 2011

Fridell JA, Mangus RS, Taber TE, Goble ML, Milgrom ML, Good J, Vetor R, Powelson JA. Growth of a nation part I: impact of organ donor obesity on whole‐organ pancreas transplantation. Clin Transplant 2011: 25: E225–E232. © 2011 John Wiley & Sons A/S.Abstract:  Obesity has reached epidemic proportions in the USA. Consequently, there are an increasing number of potential organ donors that are obese, but would otherwise be appropriate donors for pancreas transplantation (PTx). This is a retrospective study of all PTx performed at Indiana University between 2003 and 2009 (n = 308) comparing donors with body mass index (BMI) <25, 25–29.9, and ≥30 kg/m2. Data included recipient and donor demographics, seven and 90‐d graft loss, one‐yr pancreas, kidney (for simultaneous pancreas and kidney transplant only) and patient survival, causes of graft loss and death, peak amylase and lipase, length of stay, readmissions, complications, HbA1C, and c‐peptide. Of the 308 donors, 84 (27%) were overweight and 43 (14%) were obese. The overweight donors were significantly older, and the obese donors had hypertension significantly more frequently than the other two groups. There were no significant differences in recipient transplant demographics. There was no significant difference in length of stay or 90‐d readmissions, seven or 90‐d pancreas graft loss, one‐yr graft or patient survival, peak serum amylase or lipase, HbA1C, or c‐peptide. The incidence of post‐transplant technical, immunological, and infectious complications were similar. Although technically challenging, PTx of allografts from obese donors can be accomplished with similar results compared to normal BMI donors.
Dermoscopy: Ex vivo visualization of fleas head and bag of eggs confirms the diagnosis of Tungiasis
Authors: Dunn Rebecca , Asher Ruth , Bowling Jonathan 
Published: March 2011

ABSTRACTTungiasis, caused by the impregnated female sand flea Tunga penetrans, is increasingly common in returned travellers from endemic areas. Clinical suspicion is raised by the clinicodermoscopic correlation, leading to rapid treatment which involves extraction of the intact flea. Ex vivo dermoscopy demonstrates the parasite's head and distended abdomen full of eggs, confirming the diagnosis.