bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene diversity, agroecological structure and introgression patterns among village chicken populations across North, West and Central Africa
Authors: Leroy Grégoire , Kayang Boniface B , Youssao Issaka AK , Yapi-Gnaoré Chia V , Osei-Amponsah Richard , Loukou N’Goran E , Fotsa Jean-Claude , Benabdeljelil Khalid , Bed’hom Bertrand , Tixier-Boichard Michèle , Rognon Xavier 
Published: May 2012

Abstract

Background
Chickens represent an important animal genetic resource for improving farmers’ income in Africa. The present study provides a comparative analysis of the genetic diversity of village chickens across a subset of African countries. Four hundred seventy-two chickens were sampled in 23 administrative provinces across Cameroon, Benin, Ghana, Côte d’Ivoire, and Morocco. Geographical coordinates were recorded to analyze the relationships between geographic distribution and genetic diversity. Molecular characterization was performed with a set of 22 microsatellite markers. Five commercial lines, broilers and layers, were also genotyped to investigate potential gene flow. A genetic diversity analysis was conducted both within and between populations.

Results
High heterozygosity levels, ranging from 0.51 to 0.67, were reported for all local populations, corresponding to the values usually found in scavenging populations worldwide. Allelic richness varied from 2.04 for a commercial line to 4.84 for one population from Côte d’Ivoire. Evidence of gene flow between commercial and local populations was observed in Morocco and in Cameroon, which could be related to long-term improvement programs with the distribution of crossbred chicks. The impact of such introgressions seemed rather limited, probably because of poor adaptation of exotic birds to village conditions, and because of the consumers’ preference for local chickens. No such gene flow was observed in Benin, Ghana, and Côte d’Ivoire, where improvement programs are also less developed. The clustering approach revealed an interesting similarity between local populations found in regions sharing high levels of precipitation, from Cameroon to Côte d’Ivoire. Restricting the study to Benin, Ghana, and Côte d’Ivoire, did not result in a typical breed structure but a south-west to north-east gradient was observed. Three genetically differentiated areas (P < 0.01) were identified, matching with Major Farming Systems (namely Tree Crop, Cereal-Root Crop, and Root Crop) described by the FAO.

Conclusions
Local chickens form a highly variable gene pool constituting a valuable resource for human populations. Climatic conditions, farming systems, and cultural practices may influence the genetic diversity of village chickens in Africa. A higher density of markers would be needed to identify more precisely the relative importance of these factors.
Mcm2 phosphorylation and the response to replicative stress
Authors: Stead Brent E , Brandl Christopher J , Sandre Matthew K , Davey Megan J 
Published: May 2012

Abstract

Background
The replicative helicase in eukaryotic cells is comprised of minichromosome maintenance (Mcm) proteins 2 through 7 (Mcm2-7) and is a key target for regulation of cell proliferation. In addition, it is regulated in response to replicative stress. One of the protein kinases that targets Mcm2-7 is the Dbf4-dependent kinase Cdc7 (DDK). In a previous study, we showed that alanine mutations of the DDK phosphorylation sites at S164 and S170 in Saccharomyces cerevisiae Mcm2 result in sensitivity to caffeine and methyl methanesulfonate (MMS) leading us to suggest that DDK phosphorylation of Mcm2 is required in response to replicative stress.

Results
We show here that a strain with the mcm2 allele lacking DDK phosphorylation sites (mcm2
AA) is also sensitive to the ribonucleotide reductase inhibitor, hydroxyurea (HU) and to the base analogue 5-fluorouracil (5-FU) but not the radiomimetic drug, phleomycin. We screened the budding yeast non-essential deletion collection for synthetic lethal interactions with mcm2
AA and isolated deletions that include genes involved in the control of genome integrity and oxidative stress. In addition, the spontaneous mutation rate, as measured by mutations in CAN1, was increased in the mcm2
AA strain compared to wild type, whereas with a phosphomimetic allele (mcm2
EE) the mutation rate was decreased. These results led to the idea that the mcm2
AA strain is unable to respond properly to DNA damage. We examined this by screening the deletion collection for suppressors of the caffeine sensitivity of mcm2
AA. Deletions that decrease spontaneous DNA damage, increase homologous recombination or slow replication forks were isolated. Many of the suppressors of caffeine sensitivity suppressed other phenotypes of mcm2
AA including sensitivity to genotoxic drugs, the increased frequency of cells with RPA foci and the increased mutation rate.

Conclusions
Together these observations point to a role for DDK-mediated phosphorylation of Mcm2 in the response to replicative stress, including some forms of DNA damage. We suggest that phosphorylation of Mcm2 modulates Mcm2-7 activity resulting in the stabilization of replication forks in response to replicative stress.
Low level β-lactamase production in methicillin-resistant staphylococcus aureus strains with β-lactam antibiotics-induced vancomycin resistance
Authors: Hirao Yuriko , Ikeda-Dantsuji Yurika , Matsui Hidehito , Yoshida Masaki , Hori Seiji , Sunakawa Keisuke , Nakae Taiji , Hanaki Hideaki 
Published: May 2012

Abstract

Background
A class of methicillin-resistant Staphylococcus aureus (MRSA) shows resistance to vancomycin only in the presence of β-lactam antibiotics (BIVR). This type of vancomycin resistance is mainly attributable to the rapid depletion of free vancomycin in the presence of β-lactam antibiotics. This means that β-lactam antibiotics remain active or intact in BIVR culture, although most MRSA cells are assumed to produce β-lactamase. We hypothesised that the BIVR cells either did not harbour the β-lactamase gene, blaZ, or the gene was quiescent. We tested this hypothesis by determining β-lactamase activity and conducting PCR amplification of blaZ.

Results
Five randomly selected laboratory stock BIVR strains showed an undetectable level of β-lactamase activity and were blaZ-negative. Five non-BIVR stock strains showed an average β-lactamase activity of 2.59 ± 0.35 U. To test freshly isolated MRSA, 353 clinical isolates were collected from 11 regionally distant hospitals. Among 25 BIVR strains, only 16% and 8% were blaZ positive and β-lactamase-positive, respectively. In contrast, 95% and 61% of 328 non-BIVR strains had the blaZ gene and produced active β-lactamase, respectively. To know the mechanism of low β-lactamase activity in the BIVR cells, they were transformed with the plasmid carrying the blaZ gene. The transformants still showed a low level of β-lactamase activity that was several orders of magnitude lower than that of blaZ-positive non-BIVR cells. Presence of the β-lactamase gene in the transformants was tested by PCR amplification of blaZ using 11 pairs of primers covering the entire blaZ sequence. Yield of the PCR products was consistently low compared with that using blaZ-positive non-BIVR cells. Nucleotide sequencing of blaZ in one of the BIVR transformants revealed 10 amino acid substitutions. Thus, it is likely that the β-lactamase gene was modified in the BIVR cells to downregulate active β-lactamase production.

Conclusions
We concluded that BIVR cells gain vancomycin resistance by the elimination or inactivation of β-lactamase production, thereby preserving β-lactam antibiotics in milieu, stimulating peptidoglycan metabolism, and depleting free vancomycin to a level below the minimum inhibitory concentration of vancomycin.
Chromosome arm-specific BAC end sequences permit comparative analysis of homoeologous chromosomes and genomes of polyploid wheat
Authors: Sehgal Sunish K , Li Wanlong , Rabinowicz Pablo D , Chan Agnes , Šimková Hana , Doležel Jaroslav , Gill Bikram S 
Published: May 2012

AbstractBackgroundBread wheat, one of the world’s staple food crops, has the largest, highly repetitive and polyploid genome among the cereal crops. The wheat genome holds the key to crop genetic improvement against challenges such as climate change, environmental degradation, and water scarcity. To unravel the complex wheat genome, the International Wheat Genome Sequencing Consortium (IWGSC) is pursuing a chromosome- and chromosome arm-based approach to physical mapping and sequencing. Here we report on the use of a BAC library made from flow-sorted telosomic chromosome 3A short arm (t3AS) for marker development and analysis of sequence composition and comparative evolution of homoeologous genomes of hexaploid wheat.ResultsThe end-sequencing of 9,984 random BACs from a chromosome arm 3AS-specific library (TaaCsp3AShA) generated 11,014,359 bp of high quality sequence from 17,591 BAC-ends with an average length of 626 bp. The sequence represents 3.2% of t3AS with an average DNA sequence read every 19 kb. Overall, 79% of the sequence consisted of repetitive elements, 1.38% as coding regions (estimated 2,850 genes) and another 19% of unknown origin. Comparative sequence analysis suggested that 70-77% of the genes present in both 3A and 3B were syntenic with model species. Among the transposable elements, gypsy/sabrina (12.4%) was the most abundant repeat and was significantly more frequent in 3A compared to homoeologous chromosome 3B. Twenty novel repetitive sequences were also identified usingde novorepeat identification. BESs were screened to identify simple sequence repeats (SSR) and transposable element junctions. A total of 1,057 SSRs were identified with a density of one per 10.4 kb, and 7,928 junctions between transposable elements (TE) and other sequences were identified with a density of one per 1.39 kb. With the objective of enhancing the marker density of chromosome 3AS, oligonucleotide primers were successfully designed from 758 SSRs and 695 Insertion Site Based Polymorphisms (ISBPs). Of the 96 ISBP primer pairs tested, 28 (29%) were 3A-specific and compared to 17 (18%) for 96 SSRs.ConclusionThis work reports on the use of wheat chromosome arm 3AS-specific BAC library for the targeted generation of sequence data from a particular region of the huge genome of wheat. A large quantity of sequences were generated from the A genome of hexaploid wheat for comparative genome analysis with homoeologous B and D genomes and other model grass genomes. Hundreds of molecular markers were developed from the 3AS arm-specific sequences; these and other sequences will be useful in gene discovery and physical mapping.
Renal neutrophil gelatinase associated lipocalin expression in lipopolysaccharide-induced acute kidney injury in the rat
Authors: Han Mei , Li Ying , Liu Maodong , Li Yingmin , Cong Bin 
Published: May 2012

Abstract

Background
Neutrophil gelatinase associated lipocalin (NGAL) is a highly predictive biomarker of acute kidney injury. To understand the role of NGAL in renal injury during sepsis, we investigated the temporal changes and biological sources of NGAL in a rat model of acute kidney injury, and explored the relationship between renal inflammation, humoral NGAL and NGAL expression during endotoxemia.

Methods
To induce acute renal injury, rats were treated with lipopolysaccharide (LPS, 3.5 mg/kg, ip), and the location of NGAL mRNA was evaluated by in situ hybridization. Quantitative RT-PCR was also used to determine the dynamic changes in NGAL, tumor necrosis factor α (TNFα) and interleukin (IL)-6 mRNA expression 1, 3, 6, 12, and 24 hours following LPS treatment. The correlation among NGAL, TNFα and IL-6 was analyzed. Urinary and plasma NGAL (u/pNGAL) levels were measured, and the relationship between humoral NGAL and NGAL expression in the kidney was investigated.

Results
Renal function was affected 3–12 hours after LPS. NGAL mRNA was significantly upregulated in tubular epithelia at the same time (P < 0.001). The course of NGAL mRNA upregulation occurred in parallel with renal damage. There was a transient increase in TNFα and IL-6 mRNA levels within 3 hours following LPS administration, and a strong correlation between TNFα and NGAL mRNA (r = 0.995, P <0.001) but not with IL-6 mRNA. Both pNGAL and uNGAL levels were markedly increased compared with those in the control group (P < 0.001); however, only uNGAL levels were correlated with NGAL mRNA (r = 0.850, P <0.001).

Conclusions
NGAL upregulation is sensitive to LPS-induced renal TNFα increase and injury, which are observed in the tubular epithelia. Urinary NGAL levels accurately reflect changes in NGAL in the kidney.
Dermatology undergraduate skin cancer training: a disconnect between recommendations, clinical exposure and competence
Authors: Aldridge R Benjamin , Maxwell Susanne S , Rees Jonathan L 
Published: May 2012

Abstract

Background
Skin cancers are the most common malignancies in Caucasian populations. Non-specialists are responsible for the initial assessment of skin lesions and are required to act as the gatekeepers to dermatological cancer services in many healthcare systems. The majority of such physicians receive very limited formal undergraduate or postgraduate dermatology training. The British Association of Dermatologists (BAD) has produced guidelines that list the lesions that students should be able to diagnose on graduation and the majority of UK medical schools’ operate curricula in keeping with these. There is, however, virtually no evidence as to whether these competencies are being achieved. We set out to determine students’ competence at skin lesion diagnosis and to quantify their clinical exposure to examples of such lesions during their dermatology attachment.

Methods
Three linked studies were undertaken. In the first, students’ competence was tested by randomized slideshows of images containing the 16 lesions recommended in the UK guidelines. Students’ accuracy was tested at the beginning (Day 1) and end (Day 10) of their clinical placement, with a random sample of students retested 12 months later. Secondly, students’ exposure to these lesions was recorded during their attachments. Finally a survey of the additional dermatological resources used by the students was undertaken.

Results
Study 1: Students’ diagnostic accuracy increased from 11% on Day 1 to 33% on Day 10 (effect size +2.72). After 12 months half of this effect had disappeared and the students accuracy had dropped to 24%. Study 2: Students’ exposure to the recommended lesions was poor with 82% not even witnessing a single example of each of the 3 major skin cancers. Despite these measurements, only a minority of students reported that they were not confident at diagnosing skin tumours. Study 3: The majority of students use additional resources to supplement their learning.

Conclusions
In the light of what we know about learning in dermatology, our data would suggest, that the current (traditional) undergraduate attachment is inadequate to meet the UK recommendations for graduate competence. As well as critically examining the basis for these recommendations, we need more empirical data on student performance and exposure, in order to improve teaching and learning.
Metabolic flux profiling of recombinant protein secreting Pichia pastoris growing on glucose:methanol mixtures
Authors: Jordà Joel , Jouhten Paula , Cámara Elena , Maaheimo Hannu , Albiol Joan , Ferrer Pau 
Published: May 2012

Abstract

Background
The methylotrophic yeast Pichia pastoris has emerged as one of the most promising yeast hosts for the production of heterologous proteins. Mixed feeds of methanol and a multicarbon source instead of methanol as sole carbon source have been shown to improve product productivities and alleviate metabolic burden derived from protein production. Nevertheless, systematic quantitative studies on the relationships between the central metabolism and recombinant protein production in P. pastoris are still rather limited, particularly when growing this yeast on mixed carbon sources, thus hampering future metabolic network engineering strategies for improved protein production.

Results
The metabolic flux distribution in the central metabolism of P. pastoris growing on a mixed feed of glucose and methanol was analyzed by Metabolic Flux Analysis (MFA) using 13C-NMR-derived constraints. For this purpose, we defined new flux ratios for methanol assimilation pathways in P. pastoris cells growing on glucose:methanol mixtures. By using this experimental approach, the metabolic burden caused by the overexpression and secretion of a Rhizopus oryzae lipase (Rol) in P. pastoris was further analyzed. This protein has been previously shown to trigger the unfolded protein response in P. pastoris. A series of 13C-tracer experiments were performed on aerobic chemostat cultivations with a control and two different Rol producing strains growing at a dilution rate of 0.09 h−1 using a glucose:methanol 80:20 (w/w) mix as carbon source.
The MFA performed in this study reveals a significant redistristribution of carbon fluxes in the central carbon metabolism when comparing the two recombinant strains vs the control strain, reflected in increased glycolytic, TCA cycle and NADH regeneration fluxes, as well as higher methanol dissimilation rates.

Conclusions
Overall, a further 13C-based MFA development to characterise the central metabolism of methylotrophic yeasts when growing on mixed methanol:multicarbon sources has been implemented, thus providing a new tool for the investigation of the relationships between central metabolism and protein production. Specifically, the study points at a limited but significant impact of the conformational stress associated to secretion of recombinant proteins on the central metabolism, occurring even at modest production levels.
Automated red blood cell exchange as an adjunctive treatment for severe Plasmodium falciparum malaria at the Vienna General Hospital in Austria: a retrospective cohort study
Authors: Auer-Hackenberg Lorenz , Staudinger Thomas , Bojic Andja , Locker Gottfried , Leitner Gerda C , Graninger Wolfgang , Winkler Stefan , Ramharter Michael , Worel Nina 
Published: May 2012

Abstract

Background
Severe falciparum malaria is associated with considerable rates of mortality, despite the administration of appropriate anti-malarial treatment. Since overall survival is associated with total parasite biomass, blood exchange transfusion has been proposed as a potential method to rapidly reduce peripheral parasitaemia. However, current evidence suggests that this treatment modality may not improve outcome. Automated red blood cell exchange (also referred to as “erythrocytapheresis”) has been advocated as an alternative method to rapidly remove parasites from circulating blood without affecting patients’ volume and electrolyte status. However, only limited evidence from case reports and case series is available for this adjunctive treatment. This retrospective cohort study describes the use of automated red blood cell exchange for the treatment of severe malaria at the Medical University of Vienna.

Methods
Epidemiologic data for imported malaria cases in Austria are reported and data of patients treated for malaria at the General Hospital/Medical University of Vienna were extracted from electronic hospital records.

Results
Between 2000 and 2010, 146 patients were hospitalized at the Medical University of Vienna due to malaria and 16 of those were classified as severe malaria cases. Eleven patients of this cohort were potentially eligible for an adjunctive treatment with automated red blood cell exchange. Five patients eventually underwent this procedure within a period of seven hours (range: 3–19 hours) after hospital admission. Six patients did not undergo this adjunctive treatment following the decision of the treating physician. The procedure was well tolerated in all cases and rapid reduction in parasite counts was achieved without occurrence of haemodynamic complications. One patient died within seven days, whereas four patients survived without any sequelae.

Discussion and conclusion
Automated red blood cell exchange was a safe and efficient procedure to rapidly clear peripheral parasitaemia. Whether the fast reduction in parasite biomass may ultimately improve patient survival remains however unclear. Randomized controlled trials are needed to conclusively appreciate the value of this adjunctive treatment.
CT-guided percutaneous microwave ablation of pulmonary malignancies: Results in 69 cases
Authors: Lu Qiang , Cao Wei , Huang Lijun , Wan Yi , Liu Tonggang , Cheng Qingshu , Han Yong , Li Xiaofei 
Published: May 2012

Abstract

Background
Microwave ablation (MWA) has attracted a worldwide attention gradually in treating inoperable pulmonary malignancies. However, in the lung tissues treated with MWA recurrence of tumor may still occur and few data in large patient groups till now were reported about the safety or effectiveness of microwave ablation in treating primary lung cancer and metastatic pulmonary malignancies. The purpose of this study is to evaluate the clinical curative effect (local control, survival data) MWA and its safety as well.

Methods
From 1 January 2005 to 1 January 2008, retrospective analyses, 69 patients underwent computed tomography (CT)-guided percutaneous MWA of pulmonary malignancies. All patients were deemed medically inoperable. The correlation of tumor sizes and local progression after ablation was analyzed and the survival rates within 3 years post surgery were compared between non-small-cell lung cancer and pulmonary metastases groups also.

Results
Pneumothorax was the most frequent complication and occurred in 24.64% patients after ablation. Neither needle track implantation was found nor did patient death occur in these patients within 30 days. The 1-, 2-, and 3-year overall survival rates were 66.7%, 44.9% and 24.6%, respectively. The overall survival rates for NSCLC patients in 1 year, 2 years, and 3 years were 75.0%, 54.2%, and 29.2%, respectively. The overall survival rates for pulmonary metastatic tumor patients in 1 year, 2 years, and 3 years were 47.6%, 23.8%, and 14.3%, respectively. The recurrence-free survival rates for NSCLC patients in 1 year, 2 years, and 3 years were 72.9%, 50.0%, and 27.1%, respectively. The mortality rates for pulmonary metastatic tumor patients in 1 year, 2 years, and 3 years were 47.6%, 19.0%, and 14.3%, respectively.

Conclusions
Percutaneous microwave coagulation therapy was one safe and effective method and could be beneficial for the improvement of inoperable pulmonary malignancies treatment effect.