bluuebunny/crossref_metadata_2025 huggingface dataset:
Saxagliptin and sitagliptin in adult patients with type 2 diabetes: a systematic review and meta‐analysis
Authors: Gerrald K. R. , Van Scoyoc E. , Wines R. C. , Runge T. , Jonas D. E.
Published: November 2011

The objective of this study is to compare the efficacy and safety of sitagliptin and saxagliptin with placebo and other hypoglycaemic medications in adults with type 2 diabetes. We searched MEDLINE®, Embase, the Cochrane Library and the International Pharmaceuticals from their inception through 3 February 2011. Studies were included of adults with type 2 diabetes that were 12 weeks or more in duration. Meta‐analyses were conducted when included studies were homogenous enough to justify combining their results. A total of 32 articles met inclusion criteria. Sitagliptin 100 mg monotherapy and saxagliptin 5 mg resulted in greater HbA1c reduction compared to placebo [weighted mean difference (WMD) −0.82%, 95% CI −0.95 to −0.70 and WMD −0.70, 95% CI −0.84 to −0.56, respectively]. Sitagliptin was similar to sulfonylureas for HbA1c reduction (WMD 0.08%, 95% CI 0–0.16, 3 trials) and to saxagliptin in one head‐to‐head trial. There was no statistically significant difference in hypoglycaemia between sitagliptin (pooled RR 1.55, 95% CI 0.55–4.36) or saxagliptin (pooled RR 1.04, 95% CI 0.28–3.81) and placebo. Sitagliptin and saxagliptin result in similar modest HbA1c reductions and do not increase the risk of hypoglycaemia unless combined with other therapies. Their role in the long‐term treatment of type 2 diabetes remains unclear given the lack of long‐term data on efficacy, harms and health outcomes.
Prevalence of melanocytic nevi in 8‐ to 10‐year‐old children in Southern Spain and analysis of associated factors
Authors: Buendía‐Eisman A. , Paláu‐Lázaro M.C. , Arias‐Santiago S. , Cabrera‐León A. , Serrano‐Ortega S.
Published: November 2011

Background  There is a known relationship between melanocytic nevi (MN) and cutaneous melanoma. MN are related to genetic and environmental factors, and the latter appear to be more important in childhood.

Objectives  To determine the prevalence of MN and its relationship with phenotypic traits and sun exposure habits in 8‐ to 10‐year‐old children.

Subjects and methods  We performed a cross‐sectional study of 8‐ to 10‐year‐old primary school children in the city of Granada (Spain), gathering data on phenotypic traits, sun protection measures, sunburn frequency and the number and density of MN.

Results  We detected a mean of 19.38 MN per child, predominantly <2 mm in diameter. MN count was associated with low phototype, and was higher in boys vs. girls with low phototype. MN were more numerous with higher age. The largest number of MN of all sizes was detected in 10‐year‐old boys. MN were most frequently located on the torso and other sites intermittently exposed to sunlight.

Conclusions  A higher MN count is associated with lower phototype (blonde hair and fair skin) and higher age. The mean number of MN, including those of smaller size (<2 mm), was elevated in our series, especially on intermittently exposed sites.
Illness burden and medical comorbidity in the Systematic Treatment Enhancement Program for Bipolar Disorder
Authors: Magalhães P. V. , Kapczinski F. , Nierenberg A. A. , Deckersbach T. , Weisinger D. , Dodd S. , Berk M.
Published: November 2011

Magalhães PV, Kapczinski F, Nierenberg AA, Deckersbach T, Weisinger D, Dodd S, Berk M. Illness burden and medical comorbidity in the Systematic Treatment Enhancement Program for Bipolar Disorder.

Objective:  Coexisting chronic medical conditions are common in bipolar disorder. Here, we report the prevalence and correlates of medical comorbidity in patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP‐BD). We were particularly interested in associations between variables reflecting illness chronicity and burden with comorbid medical conditions.

Method:  We used intake data from the open‐label component of the STEP‐BD. History of medical comorbidity was obtained from the affective disorders evaluation, and its presence was the outcome of interest. The sample size in analyses varied from 3399 to 3534. We used multiple Poisson regression to obtain prevalence ratios.

Results:  The prevalence of any medical comorbidity in the sample was 58.8%. In addition to demographic variable, several clinical characteristics were associated with the frequency of medical comorbidity. Having more than 10 previous mood episodes, childhood onset, smoking, lifetime comorbidity with anxiety, and substance use disorders were independently associated with having a medical comorbidity in the final multivariate model.

Conclusion:  The results presented here reveal strong associations between variables related to illness chronicity and medical burden in bipolar disorder. This lends further support to recent multidimensional models incorporating medical morbidity as a core feature of bipolar disorder.
The relationship between osteoporosis and periodontitis in women aged 45–70 years
Authors: Pepelassi E , Nicopoulou‐Karayianni K , Archontopoulou AD , Mitsea A , Kavadella A , Tsiklakis K , Vrotsos I , Devlin H , Horner K
Published: November 2011

Oral Diseases (2012) 18, 353–359

Objective:  To explore the possible relationship between the osteoporotic condition and the severity of periodontitis in women aged 45–70 years.

Materials and Methods:  Ninety women with generalized chronic periodontitis, aged 45–70 years, were studied. Areal bone mineral density (BMDa) was assessed using standardized dual energy X‐ray absorptiometry (normal: T‐score ≥ −1, osteopenic: −2.5 ≤ T‐score <−1, osteoporotic: T‐score < −2.5). Gingival index (GI), bleeding on probing, clinical attachment loss (CAL), probing pocket depth and gingival recession (GR) were recorded. Periodontitis severity was represented by CAL. Menopausal condition and smoking were documented.

Results:  Mean GI, bleeding on probing, CAL and GR were significantly greater for osteoporotic women than women with normal BMDa (P = 0.002, P = 0.01, P = 0.04, respectively). Osteopenic women and women with normal BMDa significantly differed in mean GI (P = 0.02). The associations found between osteoporotic women and women with normal BMDa and the associations found between osteopenic women and women with normal BMDa existed even after adjusting for smoking and menopausal status.

Conclusion:  Subjects with osteoporosis (OPR) presented with greater CAL than the subjects with normal BMDa, which suggests a greater severity of periodontitis. Subjects with OPR had greater GR than the subjects with normal BMDa. Subjects with osteopenia and subjects with normal BMDa did not differ in CAL, which might suggest that the early diagnosis of reduced BMDa, prior to the establishment of a significant negative impact on the periodontal tissues, might be important. Smoking and menopausal status did not alter these associations.
Loss of implant‐bone interface following distal radial locking‐plate endoprosthesis limb‐sparing surgery in a dog
Authors: Venzin C. , Grundmann S. , Montavon P. M.
Published: November 2011

An eight‐year‐old, neutered female Rottweiler was presented with lameness of seven days duration. Radiographs were consistent with a distal radial bone tumour. Limb‐sparing surgery was performed using a commercially available endoprosthesis with a locking bone plate. Histopathological examination of the resected bone revealed an intraosseous fibrosarcoma, and postoperative adjuvant chemotherapy was initiated three weeks after surgery. Despite initial satisfactory limb function, lameness worsened four months after surgery. Radiographs revealed large areas of bone lysis around the proximal and distal screws, leading to significant resorption of the radius and radial carpal bone with subsequent construct failure. Further treatment was declined by the owner and the dog was subsequently euthanased. This case illustrates that implant failure is not necessarily averted by the use of locking (compared with non‐locking) implants combined with an endoprosthesis to treat distal radial tumours in dogs.
Clinical signs and left atrial size in cats with cardiovascular disease in general practice
Authors: Smith S. , Dukes‐McEwan J.
Published: November 2011

Objectives: To evaluate population characteristics, clinical signs and simple echocardiographic measurements of a general practice population of cats, in identifying characteristics that reliably distinguish cats with heart disease from others, including those with respiratory disease, using widely available techniques.

Methods: Cats presented with heart disease (n=103), respiratory disease (n=19) and a normal group (n=29) were prospectively recruited. All cats were subject to full clinical examination, echocardiography and additional diagnostic procedures as appropriate to establish definitive diagnosis. Cats were classified as Group 1: no heart disease ± respiratory disease; Group 2: heart disease with no clinical signs; Group 3: heart disease with clinical signs. Murmur, gallop sound and arrhythmia prevalence and left atrial size were compared between the groups.

Results: Low heart rates prevailed in Group 3. Murmurs were prevalent in Group 2, but in Group 3 prevalence was significantly lower. Dyspnoea, gallop sounds, arrhythmias and left atrial diameter were significantly different between groups.

ClinicalSignificance: Heart rate is unreliable for diagnosing heart failure in cats. Absence of murmur is prevalent in cats with clinical signs of heart failure, but arrhythmia and gallop sounds are prevalent. Echocardiographic measurement of left atrial diameter >16.5 mm may distinguish heart failure from respiratory disease in general practice.
Treatment of extrahepatic congenital portosystemic shunts in dogs – what is the evidence base?
Authors: Tivers M. S. , Upjohn M. M. , House A. K. , Brockman D. J. , Lipscomb V. J.
Published: November 2011

A variety of surgical treatments and medical therapies are recommended for dogs with extrahepatic congenital portosystemic shunts (CPSS). The objective of this review was to assess the evidence base for the management of extrahepatic CPSS in dogs. An online bibliographic search was performed in November 2010 to identify articles relating to the question “Which of the treatment options for extrahepatic CPSS in dogs offers the best short‐ and long‐term outcomes?” Articles were assigned a level of evidence based on a modified grading system. Thirty‐eight articles were included in the review. Thirty‐six articles were classified as grade 4 and two as grade 5. The timings and methods of assessment of short‐ and long‐term outcomes varied widely between studies. One prospective study (grade 4a) showed that surgically treated dogs survived significantly longer than medically treated dogs. Four retrospective studies (grade 4b) compared the outcome of two surgical techniques but there were no statistically significant differences between treatment groups in terms of complications or outcome. The review found that the evidence base for the treatment of extrahepatic CPSS is weak. There is a lack of evidence of short‐ and long‐term outcomes to recommend one treatment over another.
Type Three Effector Gene Distribution and Sequence Analysis Provide New Insights into the Pathogenicity of Plant-Pathogenic Xanthomonas arboricola
Authors: Hajri Ahmed , Pothier Joël F. , Fischer-Le Saux Marion , Bonneau Sophie , Poussier Stéphane , Boureau Tristan , Duffy Brion , Manceau Charles
Published: November 2011

Xanthomonas arboricola
is a complex bacterial species which mainly attacks fruit trees and is responsible for emerging diseases in Europe. It comprises seven pathovars (
X. arboricola
pv. pruni,
X. arboricola
pv. corylina,
X. arboricola
pv. juglandis,
X. arboricola
pv. populi,
X. arboricola
pv. poinsettiicola,
X. arboricola
pv. celebensis, and
X. arboricola
pv. fragariae), each exhibiting characteristic disease symptoms and distinct host specificities. To better understand the factors underlying this ecological trait, we first assessed the phylogenetic relationships among a worldwide collection of
X. arboricola
strains by sequencing the housekeeping gene
rpoD
. This analysis revealed that strains of
X. arboricola
pathovar populi are divergent from the main
X. arboricola
cluster formed by all other strains. Then, we investigated the distribution of 53 type III effector (T3E) genes in a collection of 57
X. arboricola
strains that are representative of the main
X. arboricola
cluster. Our results showed that T3E repertoires vary greatly between
X. arboricola
pathovars in terms of size. Indeed,
X. arboricola
pathovars pruni, corylina, and juglandis, which are responsible for economically important stone fruit and nut diseases in Europe, harbored the largest T3E repertoires, whereas pathovars poinsettiicola, celebensis, and fragariae harbored the smallest. We also identified several differences in T3E gene content between
X. arboricola
pathovars pruni, corylina, and juglandis which may account for their differing host specificities. Further, we examined the allelic diversity of eight T3E genes from
X. arboricola
pathovars. This analysis revealed very limited allelic variations at the different loci. Altogether, the data presented here provide new insights into the evolution of pathogenicity and host range of
X. arboricola
and are discussed in terms of emergence of new diseases within this bacterial species.
Casuarina Root Exudates Alter the Physiology, Surface Properties, and Plant Infectivity of Frankia sp. Strain CcI3
Authors: Beauchemin Nicholas J. , Furnholm Teal , Lavenus Julien , Svistoonoff Sergio , Doumas Patrick , Bogusz Didier , Laplaze Laurent , Tisa Louis S.
Published: November 2011

The actinomycete genus
Frankia
forms nitrogen-fixing symbioses with 8 different families of actinorhizal plants, representing more than 200 different species. Very little is known about the initial molecular interactions between
Frankia
and host plants in the rhizosphere. Root exudates are important in
Rhizobium
-legume symbiosis, especially for initiating Nod factor synthesis. We measured differences in
Frankia
physiology after exposure to host aqueous root exudates to assess their effects on actinorhizal symbioses.
Casuarina cunninghamiana
root exudates were collected from plants under nitrogen-sufficient and -deficient conditions and tested on
Frankia
sp. strain CcI3. Root exudates increased the growth yield of
Frankia
in the presence of a carbon source, but
Frankia
was unable to use the root exudates as a sole carbon or energy source. Exposure to root exudates caused hyphal “curling” in
Frankia
cells, suggesting a chemotrophic response or surface property change. Exposure to root exudates altered Congo red dye binding, which indicated changes in the bacterial surface properties at the fatty acid level. Fourier transform infrared spectroscopy (FTIR) confirmed fatty acid changes and revealed further carbohydrate changes.
Frankia
cells preexposed to
C. cunninghamiana
root exudates for 6 days formed nodules on the host plant significantly earlier than control cells. These data support the hypothesis of early chemical signaling between actinorhizal host plants and
Frankia
in the rhizosphere.
Identification and Characterization of a Xyloglucan-Specific Family 74 Glycosyl Hydrolase from Streptomyces coelicolor A3(2)
Authors: Enkhbaatar Bolormaa , Temuujin Uyangaa , Lim Ju-Hyeon , Chi Won-Jae , Chang Yong-Keun , Hong Soon-Kwang
Published: November 2011

The
sco6545
gene of
Streptomyces coelicolor
A3(2) was nominated as a putative cellulase with 863 mature-form amino acids (90.58 kDa). We overexpressed and purified Sco6545 and demonstrated that the protein is not a cellulase but a xyloglucan-specific glycosyl hydrolase which cleaves xyloglucan at unbranched glucose residues.
DECIPHER, a Search-Based Approach to Chimera Identification for 16S rRNA Sequences
Authors: Wright Erik S. , Yilmaz L. Safak , Noguera Daniel R.
Published: November 2011

DECIPHER is a new method for finding 16S rRNA chimeric sequences by the use of a search-based approach. The method is based upon detecting short fragments that are uncommon in the phylogenetic group where a query sequence is classified but frequently found in another phylogenetic group. The algorithm was calibrated for full sequences (fs_DECIPHER) and short sequences (ss_DECIPHER) and benchmarked against WigeoN (Pintail), ChimeraSlayer, and Uchime using artificially generated chimeras. Overall, ss_DECIPHER and Uchime provided the highest chimera detection for sequences 100 to 600 nucleotides long (79% and 81%, respectively), but Uchime's performance deteriorated for longer sequences, while ss_DECIPHER maintained a high detection rate (89%). Both methods had low false-positive rates (1.3% and 1.6%). The more conservative fs_DECIPHER, benchmarked only for sequences longer than 600 nucleotides, had an overall detection rate lower than that of ss_DECIPHER (75%) but higher than those of the other programs. In addition, fs_DECIPHER had the lowest false-positive rate among all the benchmarked programs (<0.20%). DECIPHER was outperformed only by ChimeraSlayer and Uchime when chimeras were formed from closely related parents (less than 10% divergence). Given the differences in the programs, it was possible to detect over 89% of all chimeras with just the combination of ss_DECIPHER and Uchime. Using fs_DECIPHER, we detected between 1% and 2% additional chimeras in the RDP, SILVA, and Greengenes databases from which chimeras had already been removed with Pintail or Bellerophon. DECIPHER was implemented in the R programming language and is directly accessible through a webpage or by downloading the program as an R package (
http://DECIPHER.cee.wisc.edu
).
Multiple Plastids Collected by the Dinoflagellate Dinophysis mitra through Kleptoplastidy
Authors: Nishitani Goh , Nagai Satoshi , Hayakawa Shiho , Kosaka Yuki , Sakurada Kiyonari , Kamiyama Takashi , Gojobori Takashi
Published: November 2011

Kleptoplastidy is the retention of plastids obtained from ingested algal prey, which may remain temporarily functional and be used for photosynthesis by the predator. We showed that the marine dinoflagellate
Dinophysis mitra
has great kleptoplastid diversity. We obtained 308 plastid
rbc
L
sequences by gene cloning from 14
D. mitra
cells and 102 operational taxonomic units (OTUs). Most sequences were new in the genetic database and positioned within Haptophyceae (227 sequences [73.7%], 80 OTUs [78.4%]), particularly within the genus
Chrysochromulina
. Others were closely related to Prasinophyceae (16 sequences [5.2%], 5 OTUs [4.9%]), Dictyochophyceae (14 sequences [4.5%], 5 OTUs [4.9%]), Pelagophyceae (14 sequences [4.5%], 1 OTU [1.0%]), Bolidophyceae (3 sequences [1.0%], 1 OTU [1.0%]), and Bacillariophyceae (1 sequence [0.3%], 1 OTU [1.0%]); however, 33 sequences (10.8%) as 9 OTUs (8.8%) were not closely clustered with any particular group. Only six sequences were identical to those of
Chrysochromulina simplex
,
Chrysochromulina hirta
,
Chrysochromulina
sp. TKB8936,
Micromonas pusilla
NEPCC29,
Micromonas pusilla
CCMP491, and an unidentified diatom. Thus, we detected >100 different plastid sequences from 14
D. mitra
cells, strongly suggesting kleptoplastidy and the need for mixotrophic prey such as
Laboea
,
Tontonia
, and
Strombidium
-like ciliates, which retain numerous symbiotic plastids from different origins, for propagation and plastid sequestration.
Electron Donors Supporting Growth and Electroactivity of Geobacter sulfurreducens Anode Biofilms
Authors: Speers Allison M. , Reguera Gemma
Published: November 2011

Geobacter
bacteria efficiently oxidize acetate into electricity in bioelectrochemical systems, yet the range of fermentation products that support the growth of anode biofilms and electricity production has not been thoroughly investigated. Here, we show that
Geobacter sulfurreducens
oxidized formate and lactate with electrodes and Fe(III) as terminal electron acceptors, though with reduced efficiency compared to acetate. The structure of the formate and lactate biofilms increased in roughness, and the substratum coverage decreased, to alleviate the metabolic constraints derived from the assimilation of carbon from the substrates. Low levels of acetate promoted formate carbon assimilation and biofilm growth and increased the system's performance to levels comparable to those with acetate only. Lactate carbon assimilation also limited biofilm growth and led to the partial oxidization of lactate to acetate. However, lactate was fully oxidized in the presence of fumarate, which redirected carbon fluxes into the tricarboxylic acid (TCA) cycle, and by acetate-grown biofilms. These results expand the known ranges of electron donors for
Geobacter
-driven fuel cells and identify microbial constraints that can be targeted to develop better-performing strains and increase the performance of bioelectrochemical systems.
Cultured Representatives of Two Major Phylogroups of Human Colonic Faecalibacterium prausnitzii Can Utilize Pectin, Uronic Acids, and Host-Derived Substrates for Growth
Authors: Lopez-Siles Mireia , Khan Tanweer M. , Duncan Sylvia H. , Harmsen Hermie J. M. , Garcia-Gil L. Jesús , Flint Harry J.
Published: November 2011

Faecalibacterium prausnitzii
is one of the most abundant commensal bacteria in the healthy human large intestine, but information on genetic diversity and substrate utilization is limited. Here, we examine the phylogeny, phenotypic characteristics, and influence of gut environmental factors on growth of
F. prausnitzii
strains isolated from healthy subjects. Phylogenetic analysis based on the 16S rRNA sequences indicated that the cultured strains were representative of
F. prausnitzii
sequences detected by direct analysis of fecal DNA and separated the available isolates into two phylogroups. Most
F. prausnitzii
strains tested grew well under anaerobic conditions on apple pectin. Furthermore,
F. prausnitzii
strains competed successfully in coculture with two other abundant pectin-utilizing species,
Bacteroides thetaiotaomicron
and
Eubacterium eligens
, with apple pectin as substrate, suggesting that this species makes a contribution to pectin fermentation in the colon. Many
F. prausnitzii
isolates were able to utilize uronic acids for growth, an ability previously thought to be confined to
Bacteroides
spp. among human colonic anaerobes. Most strains grew on
N
-acetylglucosamine, demonstrating an ability to utilize host-derived substrates. All strains tested were bile sensitive, showing at least 80% growth inhibition in the presence of 0.5 μg/ml bile salts, while inhibition at mildly acidic pH was strain dependent. These attributes help to explain the abundance of
F. prausnitzii
in the colonic community but also suggest factors in the gut environment that may limit its distribution.
Responses of MethanogenmcrAGenes and Their Transcripts to an Alternate Dry/Wet Cycle of Paddy Field Soil
Authors: Ma Ke , Conrad Ralf , Lu Yahai
Published: November 2011

Intermittent drainage can substantially reduce methane emission from rice fields, but the microbial mechanisms remain poorly understood. In the present study, we determined the rates of methane production and emission, the dynamics of ferric iron and sulfate, and the abundance of methanogenmcrAgenes (encoding the alpha subunit of methyl coenzyme M reductase) and their transcripts in response to alternate dry/wet cycles in paddy field soil. We found that intermittent drainage did not affect the growth of rice plants but significantly reduced the rates of both methane production and emission. The dry/wet cycles also resulted in shifts of soil redox conditions, increasing the concentrations of ferric iron and sulfate in the soil. Quantitative PCR analysis revealed that bothmcrAgene copies andmcrAtranscripts significantly decreased after dry/wet alternation compared to continuous flooding. Correlation and regression analyses showed that the abundance ofmcrAgenes and transcripts positively correlated with methane production potential and soil water content and negatively correlated with the concentrations of ferric iron and sulfate in the soil. However, the transcription ofmcrAgenes was reduced to a greater extent than the abundance ofmcrAgenes, resulting in very lowmcrAtranscript/gene ratios after intermittent drainage. Furthermore, terminal restriction fragment length polymorphism analysis revealed that the composition of methanogenic community remained stable under dry/wet cycles, whereas that of metabolically active methanogens strongly changed. Collectively, our study demonstrated a stronger effect of intermittent drainage on the abundance ofmcrAtranscripts than ofmcrAgenes in rice field soil.
Development of a New Strategy for Production of Medium-Chain-Length Polyhydroxyalkanoates by Recombinant Escherichia coli via Inexpensive Non-Fatty Acid Feedstocks
Authors: Wang Qin , Tappel Ryan C. , Zhu Chengjun , Nomura Christopher T.
Published: November 2011

Pseudomonas putidaKT2440 is capable of producing medium-chain-length polyhydroxyalkanoates (MCL-PHAs) when grown on unrelated carbon sources during nutrient limitation. Transcription levels of genes putatively involved in PHA biosynthesis were assessed by quantitative real-time PCR (qRT-PCR) inP. putidagrown on glycerol as a sole carbon source. The results showed that two genes,phaGand the PP0763 gene, were highly upregulated among genes potentially involved in the biosynthesis of MCL-PHAs from unrelated carbon sources. Previous studies have describedphaGas a 3-hydroxyacyl-acyl carrier protein (ACP)-coenzyme A (CoA) transferase, and based on homology, the PP0763 gene was predicted to encode a medium-chain-fatty-acid CoA ligase. High expression levels of these genes during PHA production inP. putidaled to the hypothesis that these two genes are involved in PHA biosynthesis from non-fatty acid carbon sources, such as glucose and glycerol. ThephaGppand PP0763 genes fromP. putidawere cloned and coexpressed with the engineeredPseudomonassp. 61-3 PHA synthase genephaCl(STQK)psin recombinantEscherichia coli. Up to 400 mg liter−1MCL-PHAs was successfully produced from glucose. This study has produced the largest amount of MCL-PHAs reported from non-fatty acid carbon sources in recombinantE. colito date and opens up the possibility of using inexpensive feedstocks to produce MCL-PHA polymers.
Effectiveness of a Simplified Method for Isolation of Burkholderia pseudomallei from Soil
Authors: Limmathurotsakul Direk , Wuthiekanun Vanaporn , Amornchai Premjit , Wongsuwan Gumphol , Day Nicholas P. J. , Peacock Sharon J.
Published: November 2011

Detection of environmental
Burkholderia pseudomallei
indicates a risk for melioidosis and is important for the development of a global risk map. We describe a simple method for detecting
B. pseudomallei
using direct culture of soil in enrichment broth. This gives a rate of positivity comparable to that obtained with a standard method but is cheaper and labor saving.
Iron Storage Proteins Are Essential for the Survival and Pathogenesis of Mycobacterium tuberculosis in THP-1 Macrophages and the Guinea Pig Model of Infection
Authors: Reddy P. Vineel , Puri Rupangi Verma , Khera Aparna , Tyagi Anil K.
Published: November 2011

Iron is one of the crucial elements required for the growth ofMycobacterium tuberculosis. However, excess free iron becomes toxic for the cells because it catalyzes the production of reactive oxygen radicals, leading to oxidative damage. Hence, it is essential for the pathogen to have the ability to store intracellular iron in an iron-rich environment and utilize it under iron depletion.M. tuberculosishas two iron storage proteins, namely BfrA (Rv1876; a bacterioferritin) and BfrB (Rv3841; a ferritin-like protein). However, the demonstration of biological significance requires the disruption of relevant genes and the evaluation of the resulting mutant for its ability to survive in the host and cause disease. In this study, we have disruptedbfrAandbfrBofM. tuberculosisand demonstrated that these genes are crucial for the storage and supply of iron for the growth of bacteria and to withstand oxidative stressin vitro. In addition, thebfrA bfrBdouble mutant (H37Rv ΔbfrAΔbfrB) exhibited a marked reduction in its ability to survive inside human macrophages. Guinea pigs infected with H37Rv ΔbfrAΔbfrBexhibited a marked diminution in the dissemination of the bacilli to spleen compared to that of the parental strain. Moreover, guinea pigs infected with H37Rv ΔbfrAΔbfrBexhibited significantly reduced pathological damage in spleen and lungs compared to that of animals infected with the parental strain. Our study clearly demonstrates the importance of these iron storage proteins in the survival and pathogenesis ofM. tuberculosisin the host and establishes them as attractive targets for the development of new inhibitors against mycobacterial infections.
Decreased Transport Restores Growth of a Salmonella enterica
apbC
Mutant on Tricarballylate
Authors: Boyd Jeffrey M. , Teoh Wei Ping , Downs Diana M.
Published: November 2011

Mutants of
Salmonella enterica
lacking
apbC
have nutritional and biochemical properties indicative of defects in iron-sulfur ([Fe-S]) cluster metabolism. An
apbC
mutant is unable to grow on tricarballylate as a carbon source. Based on the ability of ApbC to transfer an [Fe-S] cluster to an apoprotein, this defect was attributed to poor loading of the [Fe-S] cluster-containing TcuB enzyme. Consistent with these observations, a previous study showed that overexpression of
iscU
, which encodes an [Fe-S] cluster molecular scaffold, suppressed the tricarballylate growth defect of an
apbC
mutant (J. M. Boyd, J. A. Lewis, J. C. Escalante-Semerena, and D. M. Downs, J. Bacteriol. 190:4596–4602, 2008). In this study,
tcuC
mutations that suppress the growth defect of an
apbC
mutant by decreasing the intracellular concentration of tricarballylate are described. Collectively, the suppressor analyses support a model in which reduced TcuB activity prevents growth on tricarballylate by (i) decreasing catabolism and (ii) allowing levels of tricarballylate that are toxic to the cell to accumulate. The
apbC tcuC
mutant strains described here reveal that the balance of the metabolic network can be altered by the accumulation of deleterious metabolites.
Substrate Recognition Mechanism and Substrate-Dependent Conformational Changes of an ROK Family Glucokinase from Streptomyces griseus
Authors: Miyazono Ken-ichi , Tabei Nobumitsu , Morita Sho , Ohnishi Yasuo , Horinouchi Sueharu , Tanokura Masaru
Published: November 2011

Carbon catabolite repression (CCR) is a widespread phenomenon in many bacteria that is defined as the repression of catabolic enzyme activities for an unfavorable carbon source by the presence of a preferable carbon source. In
Streptomyces
, secondary metabolite production often is negatively affected by the carbon source, indicating the involvement of CCR in secondary metabolism. Although the CCR mechanism in
Streptomyces
still is unclear, glucokinase is presumably a central player in CCR. SgGlkA, a glucokinase from
S. griseus
, belongs to the ROK family glucokinases, which have two consensus sequence motifs (1 and 2). Here, we report the crystal structures of apo-SgGlkA, SgGlkA in complex with glucose, and SgGlkA in complex with glucose and adenylyl imidodiphosphate (AMPPNP), which are the first structures of an ROK family glucokinase. SgGlkA is divided into a small α/β domain and a large α+β domain, and it forms a dimer-of-dimer tetrameric configuration. SgGlkA binds a β-anomer of glucose between the two domains, and His157 in consensus sequence 1 plays an important role in the glucose-binding mechanism and anomer specificity of SgGlkA. In the structures of SgGlkA, His157 forms an HC3-type zinc finger motif with three cysteine residues in consensus sequence 2 to bind a zinc ion, and it forms two hydrogen bonds with the C1 and C2 hydroxyls of glucose. When the three structures are compared, the structure of SgGlkA is found to be modified by the binding of substrates. The substrate-dependent conformational changes of SgGlkA may be related to the CCR mechanism in
Streptomyces
.
Photoconversion of CO2 using copper-modified titanium dioxide nanoparticles
Authors: Wei Jing , Tan Xin , Yu Tao , Zhao Lin
Published: November 2011

A series of copper-modified titanium dioxide (Cu/TiO2) nanoparticles were synthesized via one-step sol-gel method. The crystal structure and chemical properties were characterized using X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The Cu/TiO2nanoparticles were applied to CO2photoconversion and the yield of formaldehyde was used to evaluate the photocatalytic performance. The optimum amount of copper modifying was 0.6 wt.% and the yield of formaldehyde was 946 μmol/gcatunder UV illumination for 6 h. 20 wt.% Cu/TiO2also performed a high photocatalytic activity, which yielded 433 μmol/gcatformaldehyde under UV illumination for 6 h.
N6-substituted adenosines. Cytokinin and antitumor activities
Authors: Kolyachkina Svetlana V. , Tararov Vitali I. , Alexeev Cyril S. , Krivosheev Dmitry M. , Romanov Georgy A. , Stepanova Evgenia V. , Solomko Eliso S. , Inshakov Andrey N. , Mikhailov Sergey N.
Published: November 2011

A series ofN6-adenosine derivatives were synthesized by alkylation ofN6-acetyl-2′,3′,5′-tri-O-acetyladenosine (1) with alkyl halides and alcohols. It was shown that propargyl derivative2ais a good substrate for copper(I) catalyzed Huisgen [3+2] cycloaddition with azides. This click-reaction can be used for preparation of the libraries of 1,2,3-triazolyl modified adenosines. Biological activities ofN6-adenosines were studied in two plant and six human cancer cell assays. The remarkable parallel between cytokinin and cytotoxic activities was found. The most cytokinin active compounds3c–3eat the same time appeared to be the most potent cytotoxic agents.
Problems with a great idea: referral by prehospital emergency services to a community-based falls-prevention service
Authors: Comans Tracy A , Currin Michelle L , Quinn Jamie , Tippett Vivienne , Rogers Anthea , Haines Terry P
Published: November 2011

Background and aim

Falls are the leading cause of injury in older adults. Identifying people at risk before they experience a serious fall requiring hospitalisation allows an opportunity to intervene earlier and potentially reduce further falls and subsequent healthcare costs. The purpose of this project was to develop a referral pathway to a community falls-prevention team for older people who had experienced a fall attended by a paramedic service and who were not transported to hospital. It was also hypothesised that providing intervention to this group of clients would reduce future falls-related ambulance call-outs, emergency department presentations and hospital admissions.

Methods

An education package, referral pathway and follow-up procedures were developed. Both services had regular meetings, and work shadowing with the paramedics was also trialled to encourage more referrals. A range of demographic and other outcome measures were collected to compare people referred through the paramedic pathway and through traditional pathways.

Results

Internal data from the Queensland Ambulance Service indicated that there were approximately six falls per week by community-dwelling older persons in the eligible service catchment area (south west Brisbane metropolitan area) who were attended to by Queensland Ambulance Service paramedics, but not transported to hospital during the 2-year study period (2008–2009). Of the potential 638 eligible patients, only 17 (2.6%) were referred for a falls assessment.

Conclusion

Although this pilot programme had support from all levels of management as well as from the service providers, it did not translate into actual referrals. Several explanations are provided for these preliminary findings.
The New Zealand serious non-fatal self-harm indicators: how valid are they for monitoring trends?
Authors: Gulliver Pauline , Cryer Colin , Davie Gabrielle
Published: November 2011

Background

To monitor accurately injury incidence trends, indicators should measure incidence independently of extraneous factors. Frequencies and rates of New Zealand's serious non-fatal self-harm indicators may be prone to fluctuations in reporting owing, for example, to changing social norms. Hence, they have been considered provisional.

Aim

To validate empirically the serious non-fatal self-harm indicators.

Methods

All serious non-fatal first admissions to hospital were identified and classified according to whether principal diagnosis (PDx) was injury or mental disorder, and conversely whether contributing diagnoses were mental disorder or injury. The proportion assigned self-harm external cause of injury code (E-code) was calculated for each year from 2001 to 2007. Subsequently, all cases with a self-harm E-code were identified, and the proportion with a PDx of injury and contributing diagnosis of mental disorder, or PDx of mental disorder and contributing diagnosis of injury over time, were determined.

Results

No linear changes over time were detected in the proportion of cases assigned an injury PDx, or the proportion assigned a mental disorder PDx, or the proportion with a self-harm E-code. The estimated maximum observed increase in the frequency of serious non-fatal self-harm hospitalisation explained by changes in reporting was 19– 40%.

Conclusion

Identification of serious non-fatal self-harm events using an operational definition of PDx of injury, a self-harm first listed E-code, and an appropriate severity cut-off point, is a valid method of monitoring incidence and rates in New Zealand.
Making the message meaningful: a qualitative assessment of media promoting all-terrain vehicle safety
Authors: Brann Maria , Mullins Samantha Hope , Miller Beverly K , Eoff Shane , Graham James , Aitken Mary E
Published: November 2011

Background

Millions of all-terrain vehicles (ATV) are used around the world for recreation by both adults and youth. This increase in use has led to a substantial increase in the number of injuries and fatalities each year. Effective strategies for reducing this incidence are clearly needed; however, minimal research exists regarding effective educational interventions.

Objective

This study was designed to assess rural ATV riders' preferences for and assessment of safety messages.

Methods

13 focus group discussions with youth and adult ATV riders were conducted. 88 formative research participants provided feedback on existing ATV safety materials, which was used to develop more useful ATV safety messages. 60 evaluative focus group participants critiqued the materials developed for this project.

Results

Existing ATV safety materials have limited effectiveness, in part because they may not address the content or design needs of the target population. ATV riders want educational and action-oriented safety messages that inform youth and adult riders about their responsibilities to learn, educate and implement safety behaviours (eg, appropriate-sized ATV, safety gear, solo riding, speed limits, riding locations). In addition, messages should be clear, realistic, visually appealing and easily accessible. Newly designed ATV safety materials using the acronym TRIPSS (training, ride off-road, impairment, plan ahead, safety gear, single rider) meet ATV riders' safety messaging needs.

Conclusions

To reach a target population, it is crucial to include them in the development and assessment of safety messages. Germane to this particular study, ATV riders provided essential information for creating useful ATV safety materials.
Acute phase proteins as a tool for differential diagnosis of wasting diseases in growing pigs
Authors: Quereda J. J. , Gómez S. , Seva J. , Ramis G. , Cerón J. J. , Muñoz A. , Pallarés F. J.
Published: November 2011

The concentrations of haptoglobin (Hp), C–reactive protein (CRP) and serum amyloid A (SAA) were measured in wasted pigs, first to evaluate their usefulness in the diagnosis of infectious, wasting diseases in pigs, and second, to evaluate whether their concentrations can distinguish the lymphoid depletion score in the lymph tissues of wasted affected pigs. Fifty–three wasted pigs and seven specific pathogen free (SPF) pigs were postmortem examined. Gross lesions were evaluated and samples for histopathological, immunohistochemical, molecular biology and microbiological analysis were taken. Thirty–one pigs were diagnosed as postweaning multisystemic wasting syndrome (PMWS) and 22 as porcine respiratory disease complex (PRDC). Lymphoid depletion degree in lymph tissues of PMWS and PRDC affected pigs was determined. Serum Hp was significantly higher in pigs with PRDC in comparison with the PMWS affected pigs. Serum CRP concentration was significantly lower in pigs with PRDC than in PMWS affected pigs (P<0.001). CRP and SAA levels increased with the lymphoid depletion score, presenting statistical differences between pigs with no depletion and pigs with low, moderate or severe lymphoid depletion (P<0.05, P<0.05 and P<0.001 for CRP and P<0.01, P<0.01 and P<0.01 for SAA, respectively). Hp was higher in pigs with no or low depletion compared with the pigs suffering severe lymphoid depletion (P<0.001 and P<0.05, respectively).
DEGRADABLE POLYETHYLENIMINE DERIVATIVES AS GENE CARRIERS
Authors: KIM YOU-KYOUNG , LUU QUYNH-PHUONG , ISLAM MOHAMMAD ARIFUL , CHOI YUN-JAIE , CHO CHONG-SU , JIANG HU-LIN , CHO MYUNG-HAING
Published: November 2011

Gene therapy is a treatment for inborn and acquired diseases, although the development of safe and effective gene delivery system is a great challenge to make a gene therapy a success. Viral vectors have been used in a majority of clinics because of their high transfection efficiency in vitro and in vivo. However, their use has been limited because of several drawbacks, such as induction of immune response, recombination of wild-type viruses, limitation in the size of inserted gene, and difficulty in large-scale production. Nonviral vectors have been widely proposed safe alternatives to viral vectors because they have low immunogenicity, flexibility in the size of gene to be delivered, cell targetibility, and easy scalability of production, although they have low transfection efficiency compared to viral vectors. Among nonviral vectors, polyethylenimine (PEI) has been widely used as a standard gene carriers due to its high pH-buffering capacity for endosomal escape although high-molecular-weight PEI is too toxic owing to non-degradability. Recently, many types of degradable PEI have been studied due to high transfection efficiency with lower cytotoxicity. This review explains recent progress on the development of degradable PEIs as nonviral vectors. The present paper summarizes the transfection efficiency of DNA or silencing efficiency of small interfering RNA (siRNA) based on the kinds of degradable linkage between low PEI and crosslinkers. Degradable linkages, such as ester, disulfide, imines, carbamate, amide and ketal in the degradable PEIs are covered.
FABRICATION OF FUNCTIONALLY GRADED HYDROXYAPATITE/TITANIUM OXIDE COATING VIA DROP-ON-DEMAND TECHNIQUE
Authors: CHANG L. , THIAN E. S. , SUN J. , FUH J. Y. H. , HONG G. S. , WONG Y. S. , WANG W.
Published: November 2011

Hydroxyapatite (HA) and titanium oxide (TiO2) suspensions were utilized to fabricate the functionally graded coating via the Drop-on-Demand (DOD) micro-dispensing technique. A three-layered structure was formed, with a bottom 100% TiO2 layer, an intermediate layer consisting of 50% TiO2 and 50% HA, and a top 100% HA layer. The coating was then subjected to various characterizations, including scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDS), fourier transform infrared spectroscopy (FTIR), contact angle measurement, and adhesion test. The SEM, XRD, and FTIR techniques revealed that the DOD technique did not change the morphology, phase, and chemical composition of the coating materials. In addition, EDS results demonstrated the graded elemental distribution within the layer which confirmed the versatility of the DOD technique. A coating thickness of 20 μm was achieved, with a critical load to failure at 59 mN.
Catecholamine-induced cardiac mitochondrial dysfunction and mPTP opening: protective effect of curcumin
Authors: Izem-Meziane Malika , Djerdjouri Bahia , Rimbaud Stephanie , Caffin Fanny , Fortin Dominique , Garnier Anne , Veksler Vladimir , Joubert Frederic , Ventura-Clapier Renee
Published: November 2011

The present study was designed to characterize the mitochondrial dysfunction induced by catecholamines and to investigate whether curcumin, a natural antioxidant, induces cardioprotective effects against catecholamine-induced cardiotoxicity by preserving mitochondrial function. Because mitochondria play a central role in ischemia and oxidative stress, we hypothesized that mitochondrial dysfunction is involved in catecholamine toxicity and in the potential protective effects of curcumin. Male Wistar rats received subcutaneous injection of 150 mg·kg−1·day−1 isoprenaline (ISO) for two consecutive days with or without pretreatment with 60 mg·kg−1·day−1 curcumin. Twenty four hours after, cardiac tissues were examined for apoptosis and oxidative stress. Expression of proteins involved in mitochondrial biogenesis and function were measured by real-time RT-PCR. Isolated mitochondria and permeabilized cardiac fibers were used for swelling and mitochondrial function experiments, respectively. Mitochondrial morphology and permeability transition pore (mPTP) opening were assessed by fluorescence in isolated cardiomyocytes. ISO treatment induced cell damage, oxidative stress, and apoptosis that were prevented by curcumin. Moreover, mitochondria seem to play an important role in these effects as respiration and mitochondrial swelling were increased following ISO treatment, these effects being again prevented by curcumin. Importantly, curcumin completely prevented the ISO-induced increase in mPTP calcium susceptibility in isolated cardiomyocytes without affecting mitochondrial biogenesis and mitochondrial network dynamic. The results unravel the importance of mitochondrial dysfunction in isoprenaline-induced cardiotoxicity as well as a new cardioprotective effect of curcumin through prevention of mitochondrial damage and mPTP opening.
Central neural control of sympathetic nerve activity in heart failure following exercise training
Authors: Patel Kaushik P. , Zheng Hong
Published: November 2011

Typical characteristics of chronic congestive heart failure (HF) are increased sympathetic drive, altered autonomic reflexes, and altered body fluid regulation. These abnormalities lead to an increased risk of mortality, particularly in the late stage of chronic HF. Recent evidence suggests that central nervous system (CNS) mechanisms may be important in these abnormalities during HF. Exercise training (ExT) has emerged as a nonpharmacological therapeutic strategy substitute with significant benefit to patients with HF. Regular ExT improves functional capacity as well as quality of life and perhaps prognosis in chronic HF patients. The mechanism(s) by which ExT improves the clinical status of HF patients is not fully known. Recent studies have provided convincing evidence that ExT significantly alleviates the increased sympathetic drive, altered autonomic reflexes, and altered body fluid regulation in HF. This review describes and highlights the studies that examine various central pathways involved in autonomic outflow that are altered in HF and are improved following ExT. The increased sympathoexcitation is due to an imbalance between inhibitory and excitatory mechanisms within specific areas in the CNS such as the paraventricular nucleus (PVN) of the hypothalamus. Studies summarized here have revealed that ExT improves the altered inhibitory pathway utilizing nitric oxide and GABA mechanisms within the PVN in HF. ExT alleviates elevated sympathetic outflow in HF through normalization of excitatory glutamatergic and angiotensinergic mechanisms within the PVN. ExT also improves volume reflex function and thus fluid balance in HF. Preliminary observations also suggest that ExT induces structural neuroplasticity in the brain of rats with HF. We conclude that improvement of the enhanced CNS-mediated increase in sympathetic outflow, specifically to the kidneys related to fluid balance, contributes to the beneficial effects of ExT in HF.