bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Proteins Likely To Be Involved in Morphogenesis, Cell Division, and Signal Transduction in Planctomycetes by Comparative Genomics
Authors: Jogler Christian , Waldmann Jost , Huang Xiaoluo , Jogler Mareike , Glöckner Frank Oliver , Mascher Thorsten , Kolter Roberto 
Published: September 2012

ABSTRACT

Members of the
Planctomycetes
clade share many unusual features for bacteria. Their cytoplasm contains membrane-bound compartments, they lack peptidoglycan and FtsZ, they divide by polar budding, and they are capable of endocytosis. Planctomycete genomes have remained enigmatic, generally being quite large (up to 9 Mb), and on average, 55% of their predicted proteins are of unknown function. Importantly, proteins related to the unusual traits of
Planctomycetes
remain largely unknown. Thus, we embarked on bioinformatic analyses of these genomes in an effort to predict proteins that are likely to be involved in compartmentalization, cell division, and signal transduction. We used three complementary strategies. First, we defined the
Planctomycetes
core genome and subtracted genes of well-studied model organisms. Second, we analyzed the gene content and synteny of morphogenesis and cell division genes and combined both methods using a “guilt-by-association” approach. Third, we identified signal transduction systems as well as sigma factors. These analyses provide a manageable list of candidate genes for future genetic studies and provide evidence for complex signaling in the
Planctomycetes
akin to that observed for bacteria with complex life-styles, such as
Myxococcus xanthus
.
Two Protein Lysine Methyltransferases Methylate Outer Membrane Protein B from Rickettsia
Authors: Abeykoon Amila H. , Chao Chien-Chung , Wang Guanghui , Gucek Marjan , Yang David C. H. , Ching Wei-Mei 
Published: September 2012

ABSTRACT

Rickettsia prowazekii
, the etiologic agent of epidemic typhus, is a potential biological threat agent. Its outer membrane protein B (OmpB) is an immunodominant antigen and plays roles as protective envelope and as adhesins. The observation of the correlation between methylation of lysine residues in rickettsial OmpB and bacterial virulence has suggested the importance of an enzymatic system for the methylation of OmpB. However, no rickettsial lysine methyltransferase has been characterized. Bioinformatic analysis of genomic DNA sequences of
Rickettsia
identified putative lysine methyltransferases. The genes of the potential methyltransferases were synthesized, cloned, and expressed in
Escherichia coli
, and expressed proteins were purified by nickel-nitrilotriacetic acid (Ni-NTA) affinity chromatography. The methyltransferase activities of the purified proteins were analyzed by methyl incorporation of radioactively labeled
S
-adenosylmethionine into recombinant fragments of OmpB. Two putative recombinant methyltransferases (rRP789 and rRP027-028) methylated recombinant OmpB fragments. The specific activity of rRP789 is 10- to 30-fold higher than that of rRP027-028. Western blot analysis using specific antibodies against trimethyl lysine showed that both rRP789 and rRP027-028 catalyzed trimethylation of recombinant OmpB fragments. Liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis showed that rRP789 catalyzed mono-, di-, and trimethylation of lysine, while rRP027-028 catalyzed exclusively trimethylation. To our knowledge, rRP789 and rRP027-028 are the first biochemically characterized lysine methyltransferases of outer membrane proteins from Gram-negative bacteria. The production and characterization of rickettsial lysine methyltransferases provide new tools to investigate the mechanism of methylation of OmpB, effects of methylation on the structure and function of OmpB, and development of methylated OmpB-based diagnostic assays and vaccine candidates.
Cold Shock Genes
cspA
and
cspB
from Caulobacter crescentus Are Posttranscriptionally Regulated and Important for Cold Adaptation
Authors: Mazzon Ricardo R. , Lang Elza A. S. , Silva Carolina A. P. T. , Marques Marilis V. 
Published: September 2012

ABSTRACT

Cold shock proteins (CSPs) are nucleic acid binding chaperones, first described as being induced to solve the problem of mRNA stabilization after temperature downshift.
Caulobacter crescentus
has four CSPs: CspA and CspB, which are cold induced, and CspC and CspD, which are induced only in stationary phase. In this work we have determined that the synthesis of both CspA and CspB reaches the maximum levels early in the acclimation phase. The deletion of
cspA
causes a decrease in growth at low temperature, whereas the strain with a deletion of
cspB
has a very subtle and transient cold-related growth phenotype. The
cspA cspB
double mutant has a slightly more severe phenotype than that of the
cspA
mutant, suggesting that although CspA may be more important to cold adaptation than CspB, both proteins have a role in this process. Gene expression analyses were carried out using
cspA
and
cspB
regulatory fusions to the
lacZ
reporter gene and showed that both genes are regulated at the transcriptional and posttranscriptional levels. Deletion mapping of the long 5′-untranslated region (5′-UTR) of each gene identified a common region important for cold induction, probably via translation enhancement. In contrast to what was reported for other bacteria, these cold shock genes have no regulatory regions downstream from ATG that are important for cold induction. This work shows that the importance of CspA and CspB to
C. crescentus
cold adaptation, mechanisms of regulation, and pattern of expression during the acclimation phase apparently differs in many aspects from what has been described so far for other bacteria.
Dynamic Localization of Tat Protein Transport Machinery Components in Streptomyces coelicolor
Authors: Willemse Joost , Ruban-Ośmialowska Beata , Widdick David , Celler Katherine , Hutchings Matthew I. , van Wezel Gilles P. , Palmer Tracy 
Published: September 2012

ABSTRACTThe Tat pathway transports folded proteins across the bacterial cytoplasmic membrane and is a major route of protein export in theStreptomycesgenus of bacteria. In this study, we have examined the localization of Tat components in the model organismStreptomyces coelicolorby constructing enhanced green fluorescent protein (eGFP) and mCherry fusions with the TatA, TatB, and TatC proteins. All three components colocalized dynamically in the vegetative hyphae, with foci of each tagged protein being prominent at the tips of emerging germ tubes and of the vegetative hyphae, suggesting that this may be a primary site of Tat secretion. Time-lapse imaging revealed that localization of the Tat components was highly dynamic during tip growth and again demonstrated a strong preference for apical sites in growing hyphae. During aerial hypha formation, TatA-eGFP and TatB-eGFP fusions relocalized to prespore compartments, indicating repositioning of Tat components during theStreptomyceslife cycle.
The Structure of the PapD-PapGII Pilin Complex Reveals an Open and Flexible P5 Pocket
Authors: Ford Bradley , Verger Denis , Dodson Karen , Volkan Ender , Kostakioti Maria , Elam Jennifer , Pinkner Jerome , Waksman Gabriel , Hultgren Scott 
Published: September 2012

ABSTRACT

P pili are hairlike polymeric structures that mediate binding of uropathogenic
Escherichia coli
to the surface of the kidney via the PapG adhesin at their tips. PapG is composed of two domains: a lectin domain at the tip of the pilus followed by a pilin domain that comprises the initial polymerizing subunit of the 1,000-plus-subunit heteropolymeric pilus fiber. Prior to assembly, periplasmic pilin domains bind to a chaperone, PapD. PapD mediates donor strand complementation, in which a beta strand of PapD temporarily completes the pilin domain's fold, preventing premature, nonproductive interactions with other pilin subunits and facilitating subunit folding. Chaperone-subunit complexes are delivered to the outer membrane usher where donor strand exchange (DSE) replaces PapD's donated beta strand with an amino-terminal extension on the next incoming pilin subunit. This occurs via a zip-in–zip-out mechanism that initiates at a relatively accessible hydrophobic space termed the P5 pocket on the terminally incorporated pilus subunit. Here, we solve the structure of PapD in complex with the pilin domain of isoform II of PapG (PapGIIp). Our data revealed that PapGIIp adopts an immunoglobulin fold with a missing seventh strand, complemented in parallel by the G1 PapD strand, typical of pilin subunits. Comparisons with other chaperone-pilin complexes indicated that the interactive surfaces are highly conserved. Interestingly, the PapGIIp P5 pocket was in an open conformation, which, as molecular dynamics simulations revealed, switches between an open and a closed conformation due to the flexibility of the surrounding loops. Our study reveals the structural details of the DSE mechanism.
Conserved Region 3 of Human Papillomavirus 16 E7 Contributes to Deregulation of the Retinoblastoma Tumor Suppressor
Authors: Todorovic Biljana , Hung Katherine , Massimi Paola , Avvakumov Nikita , Dick Frederick A. , Shaw Gary S. , Banks Lawrence , Mymryk Joe S. 
Published: September 2012

ABSTRACT
The human papillomavirus (HPV) E7 oncoprotein binds cellular factors, preventing or retargeting their function and thereby making the infected cell conducive for viral replication. A key target of E7 is the product of the retinoblastoma susceptibility locus (pRb). This interaction results in the release of E2F transcription factors and drives the host cell into the S phase of the cell cycle. E7 binds pRb via a high-affinity binding site in conserved region 2 (CR2) and also targets a portion of cellular pRb for degradation via the proteasome. Evidence suggests that a secondary binding site exists in CR3, and that this interaction influences pRb deregulation. Additionally, evidence suggests that CR3 also participates in the degradation of pRb. We have systematically analyzed the molecular mechanisms by which CR3 contributes to deregulation of the pRb pathway by utilizing a comprehensive series of mutations in residues predicted to be exposed on the surface of HPV16 E7 CR3. Despite differences in the ability to interact with cullin 2, all CR3 mutants degrade pRb comparably to wild-type E7. We identified two specific patches of residues on the surface of CR3 that contribute to pRb binding independently of the high-affinity CR2 binding site. Mutants within CR3 that affect pRb binding are less effective than the wild-type E7 in overcoming pRb-induced cell cycle arrest. This demonstrates that the interaction between HPV16 E7 CR3 and pRb is functionally important for alteration of the cell cycle.
Mouse Mammary Tumor Virus Suppresses Apoptosis of Mammary Epithelial Cells through ITAM-Mediated Signaling
Authors: Kim Hyoung H. , Grande Shannon M. , Monroe John G. , Ross Susan R. 
Published: September 2012

ABSTRACT

Many receptors in hematopoietic cells use a common signaling pathway that relies on a highly conserved immunoreceptor tyrosine-based activation motif (ITAM), which signals through Src family tyrosine kinases. ITAM-bearing proteins are also found in many oncogenic viruses, including the mouse mammary tumor virus (MMTV) envelope (Env). We previously showed that MMTV Env expression transformed normal mammary epithelial cells and that Src kinases were important mediators in this transformation. To study how ITAM signaling affects mammary cell transformation, we utilized mammary cell lines expressing two different ITAM-containing proteins, one encoding a MMTV provirus and the other a B cell receptor fusion protein. ITAM-expressing cells were resistant to both serum starvation- and chemotherapeutic drug-induced apoptosis, whereas cells transduced with these molecules bearing ITAM mutations were indistinguishable from untransduced cells in their sensitivity to these treatments. We also found that Src kinase was activated in the MMTV-expressing cells and that MMTV-induced apoptosis resistance was completely restored by the Src inhibitor PP2.
In vivo
, MMTV infection delayed involution-induced apoptosis in the mouse mammary gland. Our results show that MMTV suppresses apoptosis through ITAM-mediated Src tyrosine kinase signaling. These studies could lead to the development of effective treatment of nonhematopoietic cell cancers in which ITAM-mediated signaling plays a role.
A Meta-Analysis of the Efficacy of Acupuncture in Treating Dysphagia in Patients with a Stroke
Authors: Long Yao-Bin , Wu Xiao-Ping 
Published: September 2012

Background Dysphagia, or deglutition difficulty, is a common manifestation in patients with a stroke and its management is an important aspect of rehabilitation. Acupuncture, a complementary and alternative therapy, is the subject of growing public interest for treatment of stroke. Objective A meta-analysis was performed to study the effect of acupuncture for treatment of dysphagia in patients affected by a stroke. Methods Randomised controlled trials (RCTs) comparing acupuncture treatment with non-acupuncture treatment of dysphagia in patients with a stroke were identified from the databases of PubMed, Embase, Cochrane Library and CBM disc (China Biological Medicine Database). Eligible investigations were included and data on the effectiveness of acupuncture were extracted and synthesised by meta-analysis using RevMan 5.1.4. Results were expressed as OR for dichotomous data; 95% CIs were also calculated. Results Seventy-two RCTs (3208 patients in the treatment group and 2926 patients in the control group) were identified. Details of randomisation and blinding were not reported and information on withdrawals and dropouts was missing in most of included reports. Meta-analysis showed that the effectiveness of treatment in the group receiving acupuncture was higher than that in the non-acupuncture group (OR=5.17, 95% CI 4.18 to 6.38; p<0.00001). However, the study quality was generally low and of insufficient quality to make recommendations about using acupuncture in the rehabilitation of patients with dysphagia due to stroke. Conclusions Acupuncture might be beneficial in the rehabilitation of patients with dysphagia caused by stroke, and the evidence justifies future high-quality studies.
Effectiveness of telemedicine and distance learning applications for patients with chronic heart failure. A protocol for prospective parallel group non-randomised open label study
Authors: Vanagas Giedrius , Umbrasienė Jelena , Šlapikas Rimvydas ,   ICT for Health project workgroup
Published: September 2012

IntroductionChronic heart failure in Baltic Sea Region is responsible for more hospitalisations than all forms of cancer combined and is one of the leading causes of hospitalisations in elderly patients. Frequent hospitalisations, along with other direct and indirect costs, place financial burden on healthcare systems. We aim to test the hypothesis that telemedicine and distance learning applications is superior to the current standard of home care.Methods and analysisProspective parallel group non-randomised open label study in patients with New York Heart Association (NYHA) II–III chronic heart failure will be carried out in six Baltic Sea Region countries. The study is organised into two 6-month follow-up periods. The first 6-month period is based on active implementation of tele-education and/or telemedicine for patients in two groups (active run period) and one standard care group (passive run period). The second 6-month period of observation will be based on standard care model (passive run period) to all three groups. Our proposed practice change is based on translational research with empirically supported interventions brought to practice and aims to find the home care model that is most effective to patient needs.Ethics and disseminationThis study has been approved by National Bioethics Committee (2011-03-07; Registration No: BE-2-11).Trial RegistrationThis study has been registered in Australian New Zealand Clinical Trials Registry (ANZCTR) with registration number ACTRN12611000834954.
Preventing renal and cardiovascular risk by renal function assessment: insights from a cross-sectional study in low-income countries and the USA
Authors: Cravedi Paolo , Sharma Sanjib Kumar , Bravo Rodolfo Flores , Islam Nazmul , Tchokhonelidze Irma , Ghimire Madhav , Pahari Bishnu , Thapa Sanjeev , Basnet Anil , Tataradze Avtandil , Tinatin Davitaia , Beglarishvili Lela , Fwu Chyng-Wen , Kopp Jeffrey B , Eggers Paul , Ene-Iordache Bogdan , Carminati Sergio , Perna Annalisa , Chianca Antonietta , Couser William G , Remuzzi Giuseppe , Perico Norberto 
Published: September 2012

ObjectiveTo assess the prevalence of microalbuminuria and kidney dysfunction in low-income countries and in the USA.DesignCross-sectional study of screening programmes in five countries.SettingScreening programmes in Nepal, Bolivia, the USA (National Health and Nutrition Examination Survey (NHANES) 2005–2008) Bangladesh and Georgia.ParticipantsGeneral population in Nepal (n=20 811), Bolivia (n=3436) and in the USA (n=4299) and high-risk subjects in Bangladesh (n=1518) and Georgia (n=1549).Primary and secondary outcome measuresEstimated glomerular filtration rate (eGFR)<60ml/min/1.73 m2and microalbuminuria (defined as urinary albumin creatinine ratio values of 30–300 mg/g) were the main outcome measures. The cardiovascular (CV) risk was also evaluated on the basis of demographic, clinical and blood data.ResultsThe prevalence of eGFR<60ml/min/1.73 m2was 19%, 3.2% and 7% in Nepal, Bolivia and the USA, respectively. In Nepal, 7% of subjects were microalbuminuric compared to 8.6% in the USA. The prevalence of participants with predicted 10-year CV disease (CVD) risk ≥10% was 16.9%, 9.4% and 17% in Nepal, Bolivia and in the USA, respectively. In Bangladesh and Georgia, subjects with eGFR<60 ml/min/1.73 m2were 8.6% and 4.9%, whereas those with microalbuminuria were 45.4% and 56.5%, respectively. Predicted 10-year CVD risk ≥10% was 25.4% and 25% in Bangladesh and Georgia, respectively.ConclusionsRenal abnormalities are common among low-income countries and in the USA. Prevention programmes, particularly focused on those with renal abnormalities, should be established worldwide to prevent CVD and progression to end-stage renal disease.
Anabolic steroids in patients undergoing total knee arthroplasty
Authors: Metcalfe David , Watts Evan , Masters James P , Smith Neil 
Published: September 2012

ObjectivesTo systematically review the evidence for using anabolic-androgenic steroids (AAS) to aid rehabilitation following total knee replacement (TKR).DesignSystematic review of all clinical study designs.Data sourcesMEDLINE, EMBASE, AMED, CINAHL and the Cochrane Library were searched from inception to August 2012.Eligibility criteriaAll clinical study designs without language or patient demographic limits.Outcome measuresAll functional, physiological and administrative outcomes as well as reporting of adverse events.ResultsOnly two small randomised controlled trials satisfied the inclusion criteria. Statistically significant improvements were reported in the AAS group for quadriceps strength at 3 (p=0.02), 6 (p=0.01) and 12 (p=0.02) months, Functional Independence Measure score at 35 days (p=<0.05) and Knee Society Score at 6 weeks (p=0.02), 6 months (p=0.04) and 12 months (p=0.03). However, differences in hamstring strength, bone mineral density, sit-to-stand testing, walking speed, length of hospital stay and need for further inpatient rehabilitation did not reach statistical significance. There were no reported adverse events.ConclusionsThere is insufficient evidence to recommend routine administration of AAS to patients undergoing TKR. However, pilot data suggest that AAS can be administered safely and may improve important postoperative outcome measures. This justifies a randomised trial sufficiently powered to identify between-group differences likely to be of clinical significance.
Influence ofFCGR3Agenotype on the therapeutic response to rituximab in rheumatoid arthritis: an observational cohort study
Authors: Kastbom Alf , Cöster Lars , Ärlestig Lisbeth , Chatzidionysiou Aikaterini , van Vollenhoven Ronald F , Padyukov Leonid , Rantapää-Dahlqvist Solbritt , Saevarsdottir Saedis 
Published: September 2012

ObjectivesTo determine whether a polymorphism in the Fcγ receptor type IIIA (FCGR3A-F158V), influencing immunoglobulin G binding affinity, relates to the therapeutic efficacy of rituximab in rheumatoid arthritis (RA) patients.DesignObservational cohort study.SettingThree university hospital rheumatology units in Sweden.ParticipantsPatients with established RA (n=177; 145 females and 32 males) who started rituximab (Mabthera) as part of routine care.Primary outcome measuresResponse to rituximab therapy in relation to FCGR3A genotype, including stratification for sex.ResultsThe frequency of responders differed significantly acrossFCGR3Agenotypes (p=0.017 in a 3×2 contingency table). Heterozygous patients showed the highest response rate at 83%, as compared with patients carrying 158FF (68%) or 158VV (56%) (p=0.028 and 0.016, respectively). Among 158VV patients, response rates differed between male and female patients (p=0.036), but not among 158FF or 158VF patients (p=0.72 and 0.46, respectively).ConclusionsTherapeutic efficacy of rituximab in RA patients is influenced byFCGR3Agenotype, with the highest response rates found among heterozygous patients. This may suggest that different rituximab mechanisms of action in RA are optimally balanced inFCGR3A-158VF patients. Similar to the previously described associations with RA susceptibility and disease course, the impact of 158VV on rituximab response may be influenced by sex.
Hyponatraemia in patients with crush syndrome during the Wenchuan earthquake
Authors: Zhang Li , Fu Ping , Wang Li , Cai Guangyan , Zhang Lin , Chen Dezheng , Guo Dongyang , Sun Xuefeng , Chen Fuqiong , Bi Weihong , Zeng Xinjie , Li Haiyan , Liu Zhaohui , Wang Yong , Huang Songmin , Chen Xiangmei ,   for the Wenchuan earthquake-related AKI study group
Published: September 2012

BackgroundAlthough sodium disturbances are common in hospitalised patients, no study has specifically investigated the epidemiology of hyponatraemia in patients with crush syndrome.ObjectivesTo describe the incidence of hyponatraemia and assess its effect on outcome in patients with crush syndrome during the Wenchuan earthquake.MethodsA retrospective study was conducted in 17 reference hospitals during the Wenchuan earthquake. We excluded patients younger than 15 years and those with missing sodium values within 3 days after being rescued from the ruins.ResultsHyponatraemia (serum sodium concentration <135 mmol/l) was seen in 91/180 (50.6%) patients on admission. Compared with patients with normonatraemia, those with hyponatraemia were younger, had more severe traumatic injury and renal failure, underwent more fasciotomies, received more blood transfusion and renal replacement therapy. In the multivariable-adjusted model, the number of extremity injuries (OR=1.59, 95% CI 1.08 to 2.33) and serum creatinine (OR=1.30, 95% CI 1.07 to 1.59) were independently associated with the occurrence of hyponatraemia. Covariate adjusted multiple logistic regression analysis showed an independent mortality risk rising with hyponatraemia (OR=5.74, 95% CI 1.18 to 28.00).ConclusionsHyponatraemia was common in the patients with crush syndrome during the Wenchuan earthquake and associated with poor prognosis. Water, commercial drinks and hypotonic intravenous fluids should be supplied carefully to patients with crush syndrome.