bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Muconic Acid Biosynthesis Approach by Shunting Tryptophan Biosynthesis via Anthranilate
Authors: Sun Xinxiao , Lin Yuheng , Huang Qin , Yuan Qipeng , Yan Yajun 
Published: April 2013

ABSTRACT

Muconic acid is the synthetic precursor of adipic acid, and the latter is an important platform chemical that can be used for the production of nylon-6,6 and polyurethane. Currently, the production of adipic acid relies mainly on chemical processes utilizing petrochemicals, such as benzene, which are generally considered environmentally unfriendly and nonrenewable, as starting materials. Microbial synthesis from renewable carbon sources provides a promising alternative under the circumstance of petroleum depletion and environment deterioration. Here we devised a novel artificial pathway in
Escherichia coli
for the biosynthesis of muconic acid, in which anthranilate, the first intermediate in the tryptophan biosynthetic branch, was converted to catechol and muconic acid by anthranilate 1,2-dioxygenase (ADO) and catechol 1,2-dioxygenase (CDO), sequentially and respectively. First, screening for efficient ADO and CDO from different microbial species enabled the production of gram-per-liter level muconic acid from supplemented anthranilate in 5 h. To further achieve the biosynthesis of muconic acid from simple carbon sources, anthranilate overproducers were constructed by overexpressing the key enzymes in the shikimate pathway and blocking tryptophan biosynthesis. In addition, we found that introduction of a strengthened glutamine regeneration system by overexpressing glutamine synthase significantly improved anthranilate production. Finally, the engineered
E. coli
strain carrying the full pathway produced 389.96 ± 12.46 mg/liter muconic acid from simple carbon sources in shake flask experiments, a result which demonstrates scale-up potential for microbial production of muconic acid.
Mobile Elements in a Single-Filament Orange Guaymas Basin Beggiatoa (“Candidatus Maribeggiatoa”) sp. Draft Genome: Evidence for Genetic Exchange with Cyanobacteria
Authors: MacGregor Barbara J. , Biddle Jennifer F. , Teske Andreas 
Published: April 2013

ABSTRACT

The draft genome sequence of a single orange
Beggiatoa
(“
Candidatus
Maribeggiatoa”) filament collected from a microbial mat at a hydrothermal site in Guaymas Basin (Gulf of California, Mexico) shows evidence of extensive genetic exchange with cyanobacteria, in particular for sensory and signal transduction genes. A putative homing endonuclease gene and group I intron within the 23S rRNA gene; several group II catalytic introns; GyrB and DnaE inteins, also encoding homing endonucleases; multiple copies of sequences similar to the
fdxN
excision elements XisH and XisI (required for heterocyst differentiation in some cyanobacteria); and multiple sequences related to an open reading frame (ORF) (00024_0693) of unknown function all have close non-
Beggiatoaceae
matches with cyanobacterial sequences. Sequences similar to the uncharacterized ORF and Xis elements are found in other
Beggiatoaceae
genomes, a variety of cyanobacteria, and a few phylogenetically dispersed pleiomorphic or filamentous bacteria. We speculate that elements shared among filamentous bacterial species may have been exchanged in microbial mats and that some of them may be involved in cell differentiation.
Transcriptional Regulation and Characteristics of a Novel
N
-Acetylmuramoyl-
l
-Alanine Amidase Gene Involved in Bacillus thuringiensis Mother Cell Lysis
Authors: Yang Jingni , Peng Qi , Chen Zhen , Deng Chao , Shu Changlong , Zhang Jie , Huang Dafang , Song Fuping 
Published: April 2013

ABSTRACT

In
Bacillus thuringiensis
, a novel
N
-acetylmuramoyl-
l
-alanine amidase gene (named
cwlB
) was detected, and the CwlB protein was purified and characterized. Reverse transcription-PCR (RT-PCR) results indicated that
cwlB
and an upstream gene (named
cwlA
) formed one transcriptional unit. 5′ rapid amplification of cDNA ends (5′-RACE)-PCR and transcriptional fusions with the
lacZ
gene indicated that transcription of the operon was directed by a promoter, P

cwlA

, which is located upstream from the
cwlA
gene and that the transcription start site is a single 5′-end nucleotide residue T located 25 nucleotides (bp) upstream from the
cwlA
translational start codon. Moreover, the activity of P

cwlA

was controlled by σ
K
. Morphological analysis suggested that the mutation of
cwlB
could delay spore release compared to the timing of spore release in the wild-type strain. Western blot assay demonstrated that purified CwlB bound to the
B. thuringiensis
cell wall. Observations with laser confocal microscopy and a green fluorescent protein-based reporter system demonstrated that the CwlB protein localizes to the cell envelope. All results suggest that the CwlB protein is involved in mother cell lysis in
B. thuringiensis
.
Activation and Products of the Cryptic Secondary Metabolite Biosynthetic Gene Clusters by Rifampin Resistance (
rpoB
) Mutations in Actinomycetes
Authors: Tanaka Yukinori , Kasahara Ken , Hirose Yutaka , Murakami Kiriko , Kugimiya Rie , Ochi Kozo 
Published: April 2013

ABSTRACT

A subset of rifampin resistance (
rpoB
) mutations result in the overproduction of antibiotics in various actinomycetes, including
Streptomyces
,
Saccharopolyspora
, and
Amycolatopsis
, with H437Y and H437R
rpoB
mutations effective most frequently. Moreover, the
rpoB
mutations markedly activate (up to 70-fold at the transcriptional level) the cryptic/silent secondary metabolite biosynthetic gene clusters of these actinomycetes, which are not activated under general stressful conditions, with the exception of treatment with rare earth elements. Analysis of the metabolite profile demonstrated that the
rpoB
mutants produced many metabolites, which were not detected in the wild-type strains. This approach utilizing rifampin resistance mutations is characterized by its feasibility and potential scalability to high-throughput studies and would be useful to activate and to enhance the yields of metabolites for discovery and biochemical characterization.
Acute cervicitis and vulvovaginitis may be associated with Cytomegalovirus
Authors: Abou Magali , Dällenbach Patrick 
Published: April 2013

Cytomegalovirus (CMV) infection in immunocompetent hosts is generally asymptomatic or may present as a mononucleosic syndrome. Its association with acute cervicitis and vulvovaginitis has rarely been reported.A 24-year-old woman presented with pelvic pain, vulvodynia, abnormal vaginal discharge, burning with urination, fatigue, fever, vomiting and diarrhoea. The vulva and cervix were red with vesicular lesions on the cervix. Genital herpes simplex infection (HSV) was suspected and valacyclovir was given orally. However, serial viral cultures performed 7 weeks apart did not isolate HSV as suspected, but CMV was confirmed by immunofluorescence and early antigen research. Blood tests confirmed an acute CMV infection. Typical inclusions were found at histology. Symptoms resolved slowly with persistence of cervical lesions at 7 weeks from diagnosis.The frequency of CMV genital infection is probably underestimated. The infection is not always asymptomatic and might be confused with genital HSV infection. The clinical course is longer.
The experience of breast pain (mastalgia) in female runners of the 2012 London Marathon and its effect on exercise behaviour
Authors: Brown Nicola , White Jennifer , Brasher Amanda , Scurr Joanna 
Published: April 2013

BackgroundFor female marathon runners, breast pain (mastalgia) may be an important issue which has yet to be considered. This study aimed to determine the prevalence and severity of mastalgia in female marathon runners, identify factors that increase mastalgia and methods used to overcome mastalgia, and explore the impact that mastalgia may have on marathon training.Methods1397 female marathon runners were surveyed at the 2012 London Marathon Registration. All participants who completed the four-part, 30-question survey in its entirety have been included in the analysis (n=1285).Results32% of participants experienced mastalgia. This was significantly related to cup size and was greater during vigorous compared with moderate physical activity. Exercise-related factors were the primary factors reported to increase mastalgia participation. Seventeen per cent of symptomatic participants reported that mastalgia affected their exercise behaviour. Methods reportedly used to overcome mastalgia included pain medication and firm breast support; however, 44% of participants took no measures to relieve symptoms despite over half describing their mastalgia as discomforting.ConclusionsMastalgia was experienced by a third of marathon runners and was found to be related to breast size which has previously been unreported. The link between exercise and mastalgia has yet to be established; however, this study identified that exercise was the most prevalent factor in mastalgia occurrence which may have implications for its management. The number of participants who took no measures to relieve their mastalgia, or resorted to pain medication, highlights the importance and significance of research into exercise-related mastalgia.
The cost-effectiveness of total laparoscopic hysterectomy compared to total abdominal hysterectomy for the treatment of early stage endometrial cancer
Authors: Graves Nicholas , Janda Monika , Merollini Katharina , Gebski Val , Obermair Andreas ,   for the LACE trial committee
Published: April 2013

ObjectiveTo summarise how costs and health benefits will change with the adoption of total laparoscopic hysterectomy compared to total abdominal hysterectomy for the treatment of early stage endometrial cancer.DesignCost-effectiveness modelling using the information from a randomised controlled trial.ParticipantsTwo hypothetical modelled cohorts of 1000 individuals undergoing total laparoscopic hysterectomy and total abdominal hysterectomy.Outcome measuresSurgery costs; hospital bed days used; total healthcare costs; quality-adjusted life years; and net monetary benefits.ResultsFor 1000 individuals receiving total laparoscopic hysterectomy surgery, the costs were $509 575 higher, 3548 hospital fewer bed days were used and total health services costs were reduced by $3 746 221. There were 39.13 more quality-adjusted life years for a 5 year period following surgery.ConclusionsThe adoption of total laparoscopic hysterectomy is almost certainly a good decision for health services policy makers. There is 100% probability that it will be cost saving to health services, a 86.8% probability that it will increase health benefits and a 99.5% chance that it returns net monetary benefits greater than zero.
Concerning the timing of antibiotic administration in women undergoing caesarean section: a systematic review and meta-analysis
Authors: Heesen Michael , Klöhr Sven , Rossaint Rolf , Allegeaert Karel , Deprest Jan , Van de Velde Marc , Straube Sebastian 
Published: April 2013

ObjectiveTo assess the effects on maternal infectious morbidity and neonatal outcomes of the timing of antibiotic prophylaxis in women undergoing caesarean section. A recent National Institute for Health and Clinical Excellence (NICE) guideline reported that antibiotic administration before skin incision reduces the risk of maternal infection; this recommendation was based on a meta-analysis, however one including trials that were not double blind and not including a trial published recently.DesignSystematic review and meta-analysis.Data sourcesSearches of PubMed and EMBASE and reference lists of the retrieved articles.Inclusion criteriaRandomised double-blind controlled trials comparing the administration of antibiotics before skin incision with administration after cord clamping.Data extraction and analysisData on maternal total infectious morbidity, endometritis and wound infection, as well as neonatal intensive care unit admission, neonatal infection and neonatal sepsis were extracted and combined using random effects meta-analysis.ResultsFive studies reporting on 1777 parturients were included in our systematic review. The relative risk (RR) for maternal total infectious morbidity for antibiotic administration before incision compared with antibiotic administration after cord clamping was 0.64 (95% CI 0.36 to 1.15). Likewise, there was no difference in the risk of wound infection (RR 0.72, 95% CI 0.41 to 1.27). Parturients receiving the antibiotic preoperatively had a significantly reduced risk of endometritis (RR 0.48, 95% CI 0.27 to 0.87; number needed to treat 41, 95% CI 23 to 165). Analyses of the neonatal outcome parameters revealed no differences between the regimens of antibiotic administration, but were based on few studies.ConclusionsIn contrast to a recent NICE guideline, we did not find a reduction in total infectious morbidity with antibiotic administration before skin incision; we confirmed a reduction in the risk of endometritis and a lack of effect on the risk for wound infection.
Consumption of analgesics before a marathon and the incidence of cardiovascular, gastrointestinal and renal problems: a cohort study
Authors: Küster Michael , Renner Bertold , Oppel Pascal , Niederweis Ursula , Brune Kay 
Published: April 2013

ObjectivesTo prevent pain inhibiting their performance, many athletes ingest over-the-counter (OTC) analgesics before competing. We aimed at defining the use of analgesics and the relation between OTC analgesic use/dose and adverse events (AEs) during and after the race, a relation that has not been investigated to date.DesignProspective (non-interventional) cohort study, using an online questionnaire.SettingThe Bonn marathon 2010.Participants3913 of 7048 participants in the Bonn marathon 2010 returned their questionnaires.Primary and secondary outcomesIntensity of analgesic consumption before sports; incidence of AEs in the cohort of analgesic users as compared to non-users.ResultsThere was no significant difference between the premature race withdrawal rate in the analgesics cohort and the cohort who did not take analgesics (‘controls’). However, race withdrawal because of gastrointestinal AEs was significantly more frequent in the analgesics cohort than in the control. Conversely, withdrawal because of muscle cramps was rare, but it was significantly more frequent in controls. The analgesics cohort had an almost 5 times higher incidence of AEs (overall risk difference of 13%). This incidence increased significantly with increasing analgesic dose. Nine respondents reported temporary hospital admittance: three for temporary kidney failure (post-ibuprofen ingestion), four with bleeds (post-aspirin ingestion) and two cardiac infarctions (post-aspirin ingestion). None of the control reported hospital admittance.ConclusionsThe use of analgesics before participating in endurance sports may cause many potentially serious, unwanted AEs that increase with increasing analgesic dose. Analgesic use before endurance sports appears to pose an unrecognised medical problem as yet. If verifiable in other endurance sports, it requires the attention of physicians and regulatory authorities.
Cardiovascular mortality in bipolar disorder: a population-based cohort study in Sweden
Authors: Westman Jeanette , Hällgren Jonas , Wahlbeck Kristian , Erlinge David , Alfredsson Lars , Ösby Urban 
Published: April 2013

ObjectiveTo estimate the cardiovascular mortality among persons with bipolar disorder in Sweden compared to the general population.DesignPopulation register-based cohort study with a 20-year follow-up.SettingSweden.ParticipantsThe entire population of Sweden (n=10.6 million) of whom 17 101 persons were diagnosed with bipolar disorder between 1987 and 2006.Main outcome measuresMortality rate ratios (MRR), excess mortality (excess deaths), cardiovascular disorder (CVD) and specifically cerebrovascular disease, coronary heart disease, acute myocardial infarction, sudden cardiac deaths and hospital admission rate ratio (ARR).ResultsPersons with bipolar disorder died of CVD approximately 10 years earlier than the general population. One third (38%) of all deaths in persons with bipolar disorder were caused by CVD and almost half (44%) by other somatic diseases, whereas suicide and other external causes accounted for less than a fifth of all deaths (18%). Excess mortality of both CVD (n=824) and other somatic diseases (n=988) was higher than that of suicide and other external causes (n=675 deaths). MRRs for cerebrovascular disease, coronary heart disease and acute myocardial infarction were twice as high in persons with bipolar disorder compared to the general population. Despite the increased mortality of CVD, hospital admissions (ARR) for CVD treatment were only slightly increased in persons with bipolar disorder when compared to the general population.ConclusionsThe increased cardiovascular mortality in persons with bipolar disorder calls for renewed efforts to prevent and treat somatic diseases in this group. Specifically, our findings further imply that it would be critical to ensure that persons with bipolar disorder receive the same quality care for CVD as persons without bipolar disorder.
An analysis of knowledge and attitudes of hospice staff towards organ and tissue donation
Authors: Wale J , Arthur A , Faull C 
Published: April 2013

BackgroundOnly a minority of hospice patients eligible to donate tissue and organs choose to do so. Hospice care staff play a key role in discussions about donation, but their willingness to engage in these discussions and their understanding of issues around tissue and organ donation is poorly understood.AimsTo (i) identify factors associated with the wish of hospice doctors, nurses and healthcare assistants to donate their own organs after death; (ii) survey the experience of discussing the subject with patients; (iii) determine staff members’ knowledge of organ and tissue donation and (iv) identify factors associated with knowledge of organ and tissue donation.DesignCross-sectional questionnaire survey of hospice care staff.Setting/participants76 of the 94 care staff of one large UK hospice completed and returned the questionnaire.ResultsStaff wishing to donate their organs after death (43/76 56.6%) were more likely to be doctors or nurses than healthcare assistants (p=0.011) and more likely to have discussed organ or tissue donation with their family (p<0.001). Staff reporting ever having discussed donation with patients had more years’ experience (p=0.045) and had similarly discussed donation with their own family (p=0.039). Those with greater knowledge were more likely to have discussed organ or tissue donation with a patient (p=0.042).ConclusionsA reluctance to instigate discussions about organ and tissue donation may prevent palliative patients and their families being allowed the opportunity to donate. Suboptimal knowledge among hospice staff suggests the need for greater liaison between hospice staff, and the organ and tissue donation teams.
The neuter status of cats at four and six months of age is strongly associated with the owners' intended age of neutering
Authors: Welsh C. P. , Gruffydd‐Jones T. J. , Murray J. K. 
Published: April 2013

The recommended neutering age of client‐owned cats reduced recently from six to four months of age. This study assessed the proportion of cats neutered at these ages. Data were obtained from owner‐completed questionnaires at recruitment (8–16‐week‐old kittens) and 6.5–7 months of age. Demographic and lifestyle factors were assessed for potential association with neuter status using univariable and multivariable logistic regression models. Of 751 study cats, 14.1 per cent and 73.5 per cent had been neutered at (or before) four and six months of age, respectively. Multivariable analysis showed that being neutered at four months was significantly more likely for cats whose owners intended to have their cat neutered by this age, cats with a microchip, and from households in deprived regions. The likelihood of being neutered at six months of age was significantly increased for cats that were insured, obtained from an animal welfare organisation, given their second vaccination, from a household with an annual income of ≥£10 000, and owned by people intending to have their cat neutered by this age. This study suggests that while neutering rates were high at six months of age, they were low at four months of age, and that further work is required to disseminate the recommended neutering age of four months.
Body size evolution during the Triassic archosauriform radiation
Authors: Turner Alan H. , Nesbitt Sterling J. 
Published: April 2013

Abstract
The first large (>1 m) diapsids appeared near the Permian–Triassic extinction and a subset of diapsids, the archosauriforms, expanded their body size range soon after in the Early–Middle Triassic. Here, we examine body size at key evolutionary events within Archosauriformes during the Triassic and through the end-Triassic extinction. Using femoral length as a body size proxy and a temporally calibrated phylogeny of Archosauriformes, we estimate ancestral body sizes using a maximum likelihood approach and test for the presence of an adapative radiation by comparing the fit of competing evolutionary models. Archosauriform body size is characterized by punctuated change with more change occurring early in the Triassic. Archosaurs crossing the Triassic–Jurassic boundary show a wide range in ancestral size, and dinosaurs (sauropodomorphs and theropods) are considerably larger in the Jurassic. Crocodylomorph origins are characterized by a drop in body size; however, both the relative amount of change and the rate of change are matched among other archosaur clades. Archosauriforms increase in absolute body size through the Triassic and evidence suggests that a directional trend in size increase occurred in the early Mesozoic. The morphological signature of adaptive radiation is rare in comparative data from extant animals but is present at the origination of Archosauriformes.
Nkx2-8 Downregulation Promotes Angiogenesis and Activates NF-κB in Esophageal Cancer
Authors: Lin Chuyong , Song Libing , Gong Hui , Liu Aibin , Lin Xi , Wu Jueheng , Li Mengfeng , Li Jun 
Published: April 2013

Abstract
Angiogenesis is a major clinical feature of esophageal squamous cell carcinoma (ESCC), an aggressive disease of increasing incidence in developed countries. In ESCCs, the proangiogenic factor VEGF-C is an independent prognostic factor for ESCC, where understanding the mechanisms of VEGF-C upregulation may cue possible therapeutic insights. Here, we report that expression of the transcription factor Nkx2-8 is downregulated in ESCCs where it inversely correlates with progression and VEGF-C upregulation. Patients with ESCCs with lower Nkx2-8 expression exhibited reduced overall survival. Modulating expression of Nkx2-8 up or down inhibited or enhanced, respectively, proangiogenic activity in vitro and in vivo. Mechanistic investigations showed that Nkx2-8 repressed NF-κB activity by restraining nuclear localization of NF-κB p65 via downregulation of AKIP1, a NF-κB p65 binding partner, and also by directly targeting the AKIP1 promoter. We confirmed evidence for the importance of the Nkx2-8/AKIP1/NF-κB axis identified in ESCC cell models through an immunohistochemical analysis of a large cohort of human ESCC specimens. Taken together, our results showed that Nkx2-8 functions as a tumor suppressor in ESCCs, the downregulation of which contributes to NF-κB activation and ESCC angiogenesis. Cancer Res; 73(12); 3638–48. ©2013 AACR.