bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the Immunogenicity and Allergenicity of Two Cow's Milk Hydrolysates – A Study in Brown Norway Rats
Authors: Bøgh K. L. , Barkholt V. , Madsen C. B. 
Published: January 2015

AbstractHypoallergenic infant formulas based on hydrolysed milk proteins are used in the diet for cow's milk allergic infants. For a preclinical evaluation of the immunogenicity and allergenicity of new protein ingredients for such hypoallergenic infant formulas as well as for the investigation of which characteristics of hydrolysates that contribute to allergenicity, in vivo models are valuable tools. In this study, we examine the immunogenicity and allergenicity of two hydrolysates in a Brown Norway (BN) rat model, using i.p. dosing, which allows for the use of small quantities. Intact BLG, hydrolysed BLG and a hydrolysed whey product suitable for use in extensively hydrolysed formulas were thoroughly characterized for protein chemical features and administered to BN rats by i.p. immunization with or without adjuvant. Sera were analysed for specific IgG and IgE for evaluation of sensitizing capacity, immunogenicity and antibody‐binding capacity. For evaluation of eliciting capacity a skin test was performed. The study showed that the hydrolysates had no residual allergenicity, lacking the capacity to sensitize and elicit reactions in the BN rats. Dosing with or without adjuvant induced a large difference in immunogenicity. Only antibodies from rats sensitized to intact BLG with adjuvant were able to bind the hydrolysates, and the whey‐based hydrolysate only showed immunogenicity when dosed with adjuvant. This study showed that hydrolysates can be evaluated by an i.p. animal model, but that the choice of in vitro tests used for evaluation of antibody responses may greatly influence the result as well as may the use of adjuvant.
Nitrous oxide emissions in a winter wheat – summer maize double cropping system under different tillage and fertilizer management
Authors: Huang M. , Liang T. , Wang L. 
Published: January 2015

AbstractAn accurate estimation of nitrous oxide (N2O) emission from 110 million ha of upland in China is essential for the adoption of effective mitigation strategies. In this study, the effects of different tillage practices combined with nitrogen (N) fertilizer applications on N2O emission in soils were considered for a winter wheat (Triticum aestivum L.) – summer maize (Zea mays L.) double cropping system. Treatments included conventional tillage plus urea in split application (CTF1), conventional tillage with urea in a single application (CTF2), no‐tillage with straw retained plus reduced urea in a split application (NTSF1) and no‐tillage with manure plus reduced urea in a split application (NTMF1). The amounts of N input in each treatment were 285 and 225 kg N/ha for wheat and maize, respectively. Both NTSF1 and NTMF1 were found to reduce chemical N fertilizer rates by 33.3% (wheat) and 20% (maize), respectively, compared to CTF1 and CTF2. N2O emissions varied between 3.2 (NTSF1) and 9.9 (CTF2) kg N2O‐N/ha during the wheat season and between 7.6 (NTFS1) and 14.0 (NTMF1) kg N2O‐N/ha during the maize season. The yield‐based emission factors ranged from 21.9 (NTSF1) to 60.9 (CTF2) g N2O‐N/kg N for wheat and 92.5 (NTSF1) to 157.4 (NTMF1) g N2O‐N/kg N for maize. No significant effect of the treatments on crop yield was found. In addition to reducing production costs involved in land preparation, NTSF1 was shown to decrease chemical fertilizer input and mitigate N2O emissions while sustaining crop yield.
A tale of two haplotype groups: evaluating the New WorldJunoniaring species hypothesis using the distribution of divergentCOIhaplotypes
Authors: GEMMELL AMBER P. , MARCUS JEFFREY M. 
Published: January 2015

AbstractThe New WorldJunoniabutterflies are a possible ring species with a circum‐Caribbean distribution. Previous reports suggest a steady transition between North and South American forms in Mesoamerica, but in Cuba the forms were thought to co‐exist without interbreeding representing the overlapping ends of the ring. Three criteria establish the existence of a ring species: a ring‐shaped geographic distribution, gene flow among intervening forms and genetic isolation in the region of range overlap. We evaluated mitochondrialcytochrome oxidase Ihaplotypes inJunoniafrom nine species in the Western Hemisphere to test theJunoniaring species hypothesis.Junoniaspecies are generally not monophyletic with respect toCOIhaplotypes, which are shared across species. However, two majorCOIhaplotype groups exist. Group A predominates in South America, and Group B predominates in North and Central America. Therefore,COIhaplotypes can be used to assess the degree of genetic influence a population receives from each continent.Junoniashows a ring‐shaped distribution around the Caribbean, and evidence is consistent with gene flow among forms ofJunonia,including those from Mesoamerica. However, we detected no discontinuity in gene flow in Cuba or elsewhere in the Caribbean consistent with genetic isolation in the region of overlap. Although sampling is still very limited in the critical region, the only remaining possibility for a circum‐Caribbean discontinuity in gene flow is at the Isthmus of Panama, where there may be a transition from 98% Group B haplotypes in Costa Rica to 85–100% Group A haplotypes in South America.
HLAclassIIdiversity inHIV‐1 uninfected individuals from the placebo arm of theRV144Thai vaccine efficacy trial
Authors: Baldwin K. M. , Ehrenberg P. K. , Geretz A. , Prentice H. A. , Nitayaphan S. , Rerks‐Ngarm S. , Kaewkungwal J. , Pitisuttithum P. , O'Connell R. J. , Kim J. H. , Thomas R. 
Published: January 2015

AbstractTheRV144 HIVvaccine trial in Thailand elicited antibody responses to the envelope ofHIV‐1, which correlated significantly with the risk ofHIV‐1 acquisition. Human leukocyte antigen (HLA) classIImolecules are essential in antigen presentation toCD4T cells for activation of B cells to produce antibodies. We genotyped the classicalHLA‐DRB1,DQB1, andDPB1genes in 450 individuals from the placebo arm of theRV144study to determine the background allele and haplotype frequencies of these genes in this cohort. High‐resolution 4 and 6‐digit classII HLAtyping data was generated using sequencing‐based methods. The observed diversity for theHLAloci was 33HLA‐DRB1, 15HLA‐DQB1, and 26HLA‐DPB1alleles. Common alleles with frequencies greater than 10% wereDRB1*07:01,DRB1*09:01,DRB1*12:02,DRB1*15:02,DQB1*02:01/02,DQB1*03:01,DQB1*03:03,DQB1*05:01,DQB1*05:02,DPB1*04:01:01,DPB1*05:01:01, andDPB1*13:01:01. We identified 28 rare alleles with frequencies of less than 1% in the Thai individuals. Ambiguity forHLA‐DPB1*28:01in exon 2 was resolved toDPB1*296:01by next‐generation sequencing of all exons. Multi‐locus haplotypes includingHLAclass I andIIloci were reported in this study. This is the first comprehensive report of allele and haplotype frequencies of all threeHLAclassIIgenes from a Thai population. A high‐resolution genotyping method such as next‐generation sequencing avoids missing rare alleles and resolves ambiguous calls. TheHLAclassIIgenotyping data generated in this study will be beneficial not only for future disease association/vaccine efficacy studies related to theRV144study, but also for similar studies in other diseases in the Thai population, as well as population genetics and transplantation studies.
Sedimentary markers in the Provençal Basin (western Mediterranean): a window into deep geodynamic processes
Authors: Leroux Estelle , Aslanian Daniel , Rabineau Marina , Moulin Maryline , Granjeon Didier , Gorini Christian , Droz Laurence 
Published: January 2015

AbstractDeep Earth dynamics impact so strongly on surface geological processes that we can use sediment palaeo‐markers as a window into the deeper Earth. Derived from climatic and tectonic erosive actions on the continents, and related to eustasy, subsidence and isostasy, the sediment in a deep basin is the main recorder of these processes. Nevertheless, defining and quantifying the relative roles of parameters that interact to give the final sedimentary architecture is not a simple task. Using a 3D‐grid of seismic and wide‐angle data, boreholes and numerical stratigraphic modelling, we propose here a quantification of post‐rift vertical movements in the Provençal Basin (West Mediterranean) involving three domains of subsidence: seaward tilting on the platform and the slope and purely vertical subsidence in the deep basin. These domains fit the deeper crustal domains highlighted by previous geophysical data. Post‐break‐up sedimentary markers may therefore be used to identify the initial hinge lines of the rifting phase and the subsidence laws.
ENO2 activity is required for the development and reproductive success of plants, and is feedback‐repressed by AtMBP‐1
Authors: Eremina Marina , Rozhon Wilfried , Yang Saiqi , Poppenberger Brigitte 
Published: January 2015

SummaryEnolases are key glycolytic enzymes that are highly conserved in prokaryotic and eukaryotic organisms, and are among the most abundant cytosolic proteins. In this study we provide evidence that activity of the enolase ENO2 is essential for the growth and development of plants. We show that Arabidopsis plants with compromised ENO2 function, which were generated by mutating the LOS2/ENO2 locus, have severe cellular defects, including reduced cell size and defective cell differentiation with restricted lignification. At the tissue and organ level LOS2/ENO2‐deficient plants are characterized by the reduced growth of shoots and roots, altered vascular development and defective secondary growth of stems, impaired floral organogenesis and defective male gametophyte function, resulting in embryo lethality as well as delayed senescence. These phenotypes correlate with reduced lignin and increased salicylic acid contents as well as altered fatty acid and soluble sugar composition. In addition to an enolase the LOS2/ENO2 locus encodes the transcription factor AtMBP‐1, and here we reveal that this bifunctionality serves to maintain the homeostasis of ENO2 activity. In summary, we show that in plants enolase function is required for the formation of chorismate‐dependent secondary metabolites, and that this activity is feedback‐inhibited by AtMBP‐1 to enable the normal development and reproductive success of plants.
Origins of Transcriptional Transition: Balance between Upstream and Downstream Regulatory Gene Sequences
Authors: Sala Adrien , Shoaib Muhammad , Anufrieva Olga , Mutharasu Gnanavel , Yli-Harja Olli , Kandhavelu Meenakshisundaram 
Published: January 2015

ABSTRACT

By measuring individual mRNA production at the single-cell level, we investigated the
lac
promoter’s transcriptional transition during cell growth phases. In exponential phase, variation in transition rates generates two mixed phenotypes, low and high numbers of mRNAs, by modulating their burst frequency and sizes. Independent activation of the regulatory-gene sequence does not produce bimodal populations at the mRNA level, but bimodal populations are produced when the regulatory gene is activated coordinately with the upstream and downstream region promoter sequence (URS and DRS, respectively). Time-lapse microscopy of mRNAs for
lac
and a variant
lac
promoter confirm this observation. Activation of the URS/DRS elements of the promoter reveals a counterplay behavior during cell phases. The promoter transition rate coupled with cell phases determines the mRNA and transcriptional noise. We further show that bias in partitioning of RNA does not lead to phenotypic switching. Our results demonstrate that the balance between the URS and the DRS in transcriptional regulation determines population diversity.

IMPORTANCE
By measuring individual mRNA production at the single-cell level, we investigated the
lac
promoter transcriptional transition during cell growth phases. In exponential phase, variation in transition rate generates two mixed phenotypes producing low and high numbers of mRNAs by modulating the burst frequency and size. Independent activation of the regulatory gene sequence does not produce bimodal populations at the mRNA level, while it does when activated together through the coordination of upstream/downstream promoter sequences (URS/DRS). Time-lapse microscopy of mRNAs for
lac
and a
lac
variant promoter confirm this observation. Activation of the URS/DRS elements of the promoter reveals a counterplay behavior during cell phases. The promoter transition rate coupled with cell phases determines the mRNA and transcriptional noise. We further show that bias in partitioning of RNA does not lead to phenotypic switching. Our results demonstrate that the balance between URS and DRS in transcription regulation is determining the population diversity.
The Lipid-Modifying Multiple Peptide Resistance Factor Is an Oligomer Consisting of Distinct Interacting Synthase and Flippase Subunits
Authors: Ernst Christoph M. , Kuhn Sebastian , Slavetinsky Christoph J. , Krismer Bernhard , Heilbronner Simon , Gekeler Cordula , Kraus Dirk , Wagner Samuel , Peschel Andreas 
Published: January 2015

ABSTRACT

Phospholipids are synthesized at the inner leaflet of the bacterial cytoplasmic membrane but have to be translocated to the outer leaflet to maintain membrane lipid bilayer composition and structure. Even though phospholipid flippases have been proposed to exist in bacteria, only one such protein, MprF, has been described. MprF is a large integral membrane protein found in several prokaryotic phyla, whose C terminus modifies phosphatidylglycerol (PG), the most common bacterial phospholipid, with lysine or alanine to modulate the membrane surface charge and, as a consequence, confer resistance to cationic antimicrobial agents such as daptomycin. In addition, MprF is a flippase for the resulting lipids, Lys-PG or Ala-PG. Here we demonstrate that the flippase activity resides in the N-terminal 6 to 8 transmembrane segments of the
Staphylococcus aureus
MprF and that several conserved, charged amino acids and a proline residue are crucial for flippase function. MprF protects S. aureus against the membrane-active antibiotic daptomycin only when both domains are present, but the two parts do not need to be covalently linked and can function in
trans
. The Lys-PG synthase and flippase domains were each found to homo-oligomerize and also to interact with each other, which illustrates how the two functional domains may act together. Moreover, full-length MprF proteins formed oligomers, indicating that MprF functions as a dimer or larger oligomer. Together our data reveal how bacterial phospholipid flippases may function in the context of lipid biosynthetic processes.

IMPORTANCE
Bacterial cytoplasmic membranes are crucial for maintaining and protecting cellular integrity. For instance, they have to cope with membrane-damaging agents such as cationic antimicrobial peptides (CAMPs) produced by competing bacteria (bacteriocins), secreted by eukaryotic host cells (defensins), or used as antimicrobial therapy (daptomycin). The MprF protein is found in many Gram-positive, Gram-negative, and even archaeal commensals or pathogens and confers resistance to CAMPs by modifying anionic phospholipids with amino acids, thereby compromising the membrane interaction of CAMPs. Here we describe how MprF does not only modify phospholipids but uses an additional, distinct domain for translocating the resulting lysinylated phospholipids to the outer leaflet of the membrane. We reveal critical details for the structure and function of MprF, the first dedicated prokaryotic phospholipid flippase, which may pave the way for targeting MprF with new antimicrobials that would not kill bacteria but sensitize them to antibiotics and innate host defense molecules.
Clinically led performance management in secondary healthcare: evaluating the attitudes of medical and non-clinical managers
Authors: Trebble Timothy M , Paul Maureen , Hockey Peter M , Heyworth Nicola , Humphrey Rachael , Powell Timothy , Clarke Nicholas 
Published: January 2015

IntroductionImproving the quality and activity of clinicians’ practice improves patient care. Performance-related human resource management (HRM) is an established approach to improving individual practice but with limited use among clinicians. A framework for performance-related HRM was developed from successful practice in non-healthcare organisations centred on distributive leadership and locally provided, validated and interpreted performance measurement. This study evaluated the response of medical and non-clinical managers to its implementation into a large secondary healthcare organisation.MethodsA semistructured qualitative questionnaire was developed from themes identified during framework implementation and included attitudes to previous approaches to measuring doctors’ performance, and the structure and response to implementation of the performance-related HRM framework. Responses were analysed through a process of data summarising and categorising.ResultsA total of 29, from an invited cohort of 31, medical and non-clinical managers from departmental to executive level were interviewed. Three themes were identified: (1) previous systems of managing clinical performance were considered to be ineffective due to insufficient empowerment of medical managers and poor quality of available performance data; (2) the implemented framework was considered to address these needs and was positively received by medical and non-clinical managers; (3) introduction of performance-related HRM required the involvement of the whole organisation to executive level and inclusion within organisational strategy, structure and training.ConclusionsThis study suggests that a performance-related HRM framework may facilitate the management of clinical performance in secondary healthcare, but is dependent on the design and methods of application used. Such approaches contrast with those currently proposed for clinicians in secondary healthcare in the UK and suggest that alternative strategies should be considered.
Identifying clusters of falls-related hospital admissions to inform population targets for prioritising falls prevention programmes
Authors: Finch Caroline F , Stephan Karen , Shee Anna Wong , Hill Keith , Haines Terry P , Clemson Lindy , Day Lesley 
Published: January 2015

BackgroundThere has been limited research investigating the relationship between injurious falls and hospital resource use. The aims of this study were to identify clusters of community-dwelling older people in the general population who are at increased risk of being admitted to hospital following a fall and how those clusters differed in their use of hospital resources.MethodsAnalysis of routinely collected hospital admissions data relating to 45 374 fall-related admissions in Victorian community-dwelling older adults aged ≥65 years that occurred during 2008/2009 to 2010/2011. Fall-related admission episodes were identified based on being admitted from a private residence to hospital with a principal diagnosis of injury (International Classification of Diseases (ICD)-10-AM codes S00 to T75) and having a first external cause of a fall (ICD-10-AM codes W00 to W19). A cluster analysis was performed to identify homogeneous groups using demographic details of patients and information on the presence of comorbidities. Hospital length of stay (LOS) was compared across clusters using competing risks regression.ResultsClusters based on area of residence, demographic factors (age, gender, marital status, country of birth) and the presence of comorbidities were identified. Clusters representing hospitalised fallers with comorbidities were associated with longer LOS compared with other cluster groups. Clusters delineated by demographic factors were also associated with increased LOS.ConclusionsAll patients with comorbidity, and older women without comorbidities, stay in hospital longer following a fall and hence consume a disproportionate share of hospital resources. These findings have important implications for the targeting of falls prevention interventions for community-dwelling older people.
Force and aspiration analysis of the ADAPT technique in acute ischemic stroke treatment
Authors: Hu Yin C , Stiefel Michael F 
Published: January 2015

IntroductionThe development of new revascularization devices has significantly improved recanalization rates and time to reperfusion. A direct aspiration first-pass (ADAPT) technique for stroke thrombectomy was recently shown to be an effective and rapid way to achieve revascularization. The technique focuses on engaging and removing a clot without the use of a separator or retriever by relying on the force and aspiration generated by the catheter. We sought to compare the physical and fluid dynamic properties (force and aspiration) of commercially available catheters to determine the most effective catheter for the ADAPT technique.MethodsBenchtop models were employed to compare aspiration for each catheter by submersing the catheter into a graduated cylinder and aspirating water. The volume of fluid aspirated and flow rates were calculated. Force of aspiration at the tip of each catheter was measured using a vacuum pressure gauge while the catheter was attached to a standard aspiration pump. Force was then calculated.ResultsThe Penumbra 5MAX ACE catheter had the greatest aspiration rate of all the catheters at 245 mL/min. The Penumbra 5 MAX catheter aspirated 212 mL/min, followed by the Navien 058 and DAC 057 with 198 mL/min and 197 mL/min, respectively. The Penumbra 5MAX ACE generated the greatest tip force (18.25 g) and the 5MAX had the least amount of force (14.77 g).ConclusionsThe physical and fluid dynamic properties of currently available catheters suggest that the 5MAX ACE is the optimal catheter to use in direct aspiration for stroke therapy.
Short-term mortality of adult inpatients with community-acquired pneumonia: external validation of a modified CURB-65 score
Authors: Pflug Marc Andre , Tiutan Timothy , Wesemann Thomas , Nüllmann Harald , Heppner Hans Jürgen , Pientka Ludger , Thiem Ulrich 
Published: January 2015

ABSTRACT

Objective
The management of community-acquired pneumonia (CAP) continues to be a challenge, especially in older people. To enable better risk stratification, a variation of the severity scores CRB-65 and CURB-65, called CURB-age, has been suggested. We compared the association between risk groups as defined by the scores and 30-day mortality for a cohort of mainly older inpatients with CAP.

Methods
We retrospectively analysed data from the CAP database from the years 2005 to 2009 of a single centre in Herne, Germany. Patient characteristics, criteria values within the severity scores CURB-65, CRB-65 and CURB-age, and 30-day mortality were assessed. We compared the association between score points and score-defined risk groups and mortality. Sensitivity and specificity with corresponding 95% CIs were calculated, and receiver operating characteristic (ROC) curve analysis was performed.

Results
Data from 559 patients were analysed (mean age 74.1 years, 55.3% male). Mortality at day 30 was 10.9%. CURB-age included more patients in the low-risk category than CRB-65 (195 vs 89), and the patient group had a lower mortality (2.6% vs 3.4%). When compared with CURB-65, CURB-age included slightly fewer patients (195 vs 214) with lower mortality (2.6% vs 4.2%). CURB-age sorted the most patients who died within 30 days into the high-risk CAP group (CURB-age, 32; CURB-65, 28; CRB-65, 9), which had the highest mortality (CURB-age, 26.4%; CURB-65, 19.4%; CRB-65, 21.4%). Advantages of CURB-age categories were depicted through ROC curve analysis (area under the curve 0.73 (95% CI 0.67 to 0.79) for CURB-age categories, 0.67 (95% CI 0.60 to 0.74) for CURB-65 categories, and 0.59 (95% CI 0.52 to 0.66) for CRB-65 categories).

Conclusions
In comparison with CRB-65 and CURB-65, risk stratification as defined by CURB-age showed the closest association with 30-day mortality in our sample. Further prospective studies are needed to assess the potential of CURB-age for better risk prediction, especially in older patients with CAP.