bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plastidic type I signal peptidase 1 is a redox‐dependent thylakoidal processing peptidase
Authors: Midorikawa Takafumi , Endow Joshua K. , Dufour Jeremy , Zhu Jieping , Inoue Kentaro 
Published: September 2014

SummaryThylakoids are the photosynthetic membranes in chloroplasts and cyanobacteria. The aqueous phase inside the thylakoid known as the thylakoid lumen plays an essential role in the photosynthetic electron transport. The presence and significance of thiol‐disulfide exchange in this compartment have been recognized but remain poorly understood. All proteins found free in the thylakoid lumen and some proteins associated to the thylakoid membrane require an N‐terminal targeting signal, which is removed in the lumen by a membrane‐bound serine protease called thylakoidal processing peptidase (TPP). TPP is homologous to Escherichia coli type I signal peptidase (SPI) called LepB. Genetic data indicate that plastidic SPI 1 (Plsp1) is the main TPP in Arabidopsis thaliana (Arabidopsis) although biochemical evidence had been lacking. Here we demonstrate catalytic activity of bacterially produced Arabidopsis Plsp1. Recombinant Plsp1 showed processing activity against various TPP substrates at a level comparable to that of LepB. Plsp1 and LepB were also similar in the pH optima, sensitivity to arylomycin variants and a preference for the residue at −3 to the cleavage site within a substrate. Plsp1 orthologs found in angiosperms contain two unique Cys residues located in the lumen. Results of processing assays suggested that these residues were redox active and formation of a disulfide bond between them was necessary for the activity of recombinant Arabidopsis Plsp1. Furthermore, Plsp1 in Arabidopsis and pea thylakoids migrated faster under non‐reducing conditions than under reducing conditions on SDS‐PAGE. These results underpin the notion that Plsp1 is a redox‐dependent signal peptidase in the thylakoid lumen.
Blood donors in England and North Wales: demography and patterns of donation
Authors: Lattimore Samuel , Wickenden Crispin , Brailsford Susan R. 
Published: September 2014

BackgroundAs populations in the developed world shift toward an older and more ethnically diverse population, the challenges of recruiting and retaining sufficient donors to secure an adequate, safe supply of blood in the future will increase.Study Design and MethodsThe study population included all first‐time (n = 348,740) and repeat (n = 1,805,255) blood donors and their donations (n = 3,854,460) received by NHS Blood and Transplant during 2010 and 2011. Rates of new and repeat donors per 1000 population were estimated using Office for National Statistics 2011 population estimates. Factors associated with new blood donors returning within 6 months were analyzed using multivariate logistic regression.ResultsThe majority (87.9%) of donors were white British; 5.5% were unknown; 3.4% white Irish or white other; and 3.2% composed of all other ethnic groups. The median ages of new and repeat donors in 2010 were 28.0 and 45.0 years, respectively, compared to 29.0 and 47.0 years in 2011. Rates of donation varied by ethnicity, ranging from 1.59 per 1000 among Asian Bangladeshi origin, compared to 22.1 per 1000 among white British origin. Approximately two in five (38.4%) new blood donors returned within 6 months and were more likely to be male and of white ethnicity.ConclusionsBlood supply is impacted by numerous factors, including an aging population and an increasing population of migrant communities with lower donation rates. It is therefore critical that changes within the blood donor and wider population are monitored to inform donor recruitment and retention strategies.
Evaluation of acid–base disorders in dogs and cats presenting to an emergency room. Part 2: Comparison of anion gap, strong ion gap, and semiquantitative analysis
Authors: Hopper Kate , Epstein Steven E. , Kass Philip H. , Mellema Matthew S. 
Published: September 2014

AbstractObjectiveTo compare the diagnostic performance of the anion gap (AG) with 2 physicochemical approaches to identify unmeasured anions.DesignProspective cohort study.SettingUniversity teaching hospital.AnimalsEighty‐four dogs and 14 cats presenting to a university teaching hospital emergency room.InterventionsAll dogs and cats in which venous blood samples for acid–base, lactate, and serum biochemical analysis were all collected within 60 minutes of each other, over a 5‐month enrollment period. Unmeasured anions were quantified using each of three approaches: the anion gap (AG), strong ion gap (SIG), and a semiquantitative approach (XA).Measurements and Main ResultsAn increased AG metabolic acidosis was evident in 34/98 of cases. The Stewart approach identified an increased SIG acidosis in 49/98 of cases. There was a strong correlation between SIG and AG (r = 0.89; P < 0.001). The semiquantitative approach identified increased unmeasured anions in 68/98 of cases. There was a moderate correlation between AG and XA (r = 0.68; P < 0.001) and a slightly stronger correlation between SIG and XA (r = 0.75; P < 0.001). Plasma lactate concentrations and AG were poorly correlated (r = 0.22; P = 0.029) and there was no correlation between lactate concentrations and BE (r = 0.19; P = 0.069).ConclusionsUnmeasured anions occurred commonly in this sample of small animal emergency room patients and physiochemical approaches identified more animals with unmeasured anions than the traditional AG calculation. Further studies are needed to determine if the results of the physicochemical approach improves clinical management and warrants the associated increases in cost and complexity.
Descemet's membrane detachment in horses; case series and literature review
Authors: Matas Riera Màrian , Donaldson David , Priestnall Simon Lawrence 
Published: September 2014

AbstractThe aim of this article was to describe Descemet's membrane detachment (DMD) following phacoemulsification in five equine eyes and to review the human literature on this topic. In the last decade, there has been increased reporting ofDMDin the human literature, in particular following cataract surgery. The natural history ofDMDremains unknown and although various medical and surgical treatments have been advocated there is no recognized ‘gold standard’ treatment forDMD. This case series reports the diagnosis ofDMDin four horses (5 eyes) in association with phacoemulsification surgery. The diagnosis ofDMDin these patients was made intra‐operatively, postoperatively or on subsequent histopathological examination. The surgical reports, photographic or video recordings, and ultrasound data were evaluated and possible factors associated with the pathophysiology ofDMDare discussed. This is the first description ofDMDin the veterinary literature, and the authors believe thatDMDmight hitherto have been overlooked in veterinary ophthalmology due to a lack of awareness of the condition. The possible causes, clinical signs, and treatment ofDMDas described in the human literature are also reviewed.
Efficient generation of genetically distinct pigs in a single pregnancy using multiplexed single‐guide RNA and carbohydrate selection
Authors: Li Ping , Estrada Jose L. , Burlak Christopher , Montgomery Jessica , Butler James R. , Santos Rafael M. , Wang Zheng‐Yu , Paris Leela L. , Blankenship Ross L. , Downey Susan M. , Tector Matthew , Tector A. Joseph 
Published: September 2014

AbstractBackgroundManipulating the pig genome to increase compatibility with human biology may facilitate the clinical application of xenotransplantation. Genetic modifications to pig cells have been made by sequential recombination in fetal fibroblasts and liver‐derived cells followed by cross‐breeding or somatic cell nuclear transfer. The generation of pigs for research or organ donation by these methods is slow, expensive and requires technical expertise. A novel system incorporating the bacterial nuclease Cas9 and single‐guide RNA targeting a 20 nucleotide site within a gene can be expressed from a single plasmid leading to a double‐strand break and gene disruption. Coexpression of multiple unique single‐guide RNA can modify several genetic loci in a single step. We describe a process for increasing the efficiency of selecting cells with multiple genetic modifications.MethodsWe used the CRISPR/Cas system to target the GGTA1, CMAH and putative iGb3S genes in pigs that have been naturally deleted in humans. Cells lacking galactose α‐1,3 galactose (α‐Gal) were negatively selected by an IB4 lectin/magnetic bead. α‐Gal negative multiplexed single‐guide RNA‐treated cells were used for somatic cell nuclear transfer (SCNT) and transferred to fertile sows. We examined the levels of α‐Gal and Neu5Gc expression of 32 day fetuses and piglets and analyzed the targeted genes by DNA sequencing.ResultsLiver‐derived cells treated with multiple single‐guide RNA and selected for an α‐Gal null phenotype were significantly more likely to also carry mutations in simultaneously targeted genes. Multiplex single‐guide RNA‐treated cells used directly for SCNT without further genetic selection produced piglets with deletions in the targeted genes but also created double‐ and triple‐gene KO variations. CRISPR/Cas‐treated cells grew normally and yielded normal liters of healthy piglets via somatic cell nuclear transfer.ConclusionsThe CRISPR/Cas system allows targeting of multiple genes in a single reaction with the potential to create pigs of one genetic strain or multiple genetic modifications in a single pregnancy. The application of this phenotypic selection strategy with multiplexed sgRNA and the Cas9 nuclease has accelerated our ability to produce and evaluate pigs important to xenotransplantation.
The Sweet Tooth of Bacteria: Common Themes in Bacterial Glycoconjugates
Authors: Tytgat Hanne L. P. , Lebeer Sarah 
Published: September 2014

SUMMARY

Humans have been increasingly recognized as being superorganisms, living in close contact with a microbiota on all their mucosal surfaces. However, most studies on the human microbiota have focused on gaining comprehensive insights into the composition of the microbiota under different health conditions (e.g., enterotypes), while there is also a need for detailed knowledge of the different molecules that mediate interactions with the host. Glycoconjugates are an interesting class of molecules for detailed studies, as they form a strain-specific barcode on the surface of bacteria, mediating specific interactions with the host. Strikingly, most glycoconjugates are synthesized by similar biosynthesis mechanisms. Bacteria can produce their major glycoconjugates by using a sequential or an
en bloc
mechanism, with both mechanistic options coexisting in many species for different macromolecules. In this review, these common themes are conceptualized and illustrated for all major classes of known bacterial glycoconjugates, with a special focus on the rather recently emergent field of glycosylated proteins. We describe the biosynthesis and importance of glycoconjugates in both pathogenic and beneficial bacteria and in both Gram-positive and -negative organisms. The focus lies on microorganisms important for human physiology. In addition, the potential for a better knowledge of bacterial glycoconjugates in the emerging field of glycoengineering and other perspectives is discussed.
A transient peak of infections during onset of rheumatoid arthritis: a 10-year prospective cohort study
Authors: Arleevskaya Marina I , Gabdoulkhakova Aida G , Filina Yulia V , Miftakhova Regina R , Bredberg Anders , Tsybulkin Anatoly P 
Published: September 2014

ObjectivesThe role of infection in rheumatoid arthritis (RA) has not been determined. We aimed to document the infectious burden and some aspects of antibacterial immunity in a large and prospective cohort study of RA patients in the early and late stages of the disease and in their relatives predisposed to RA.SettingClinical and laboratory examination of all individuals enrolled in the study was performed in the Republican Clinical Hospital, Kazan, Russia.Participants376 patients with RA, 251 healthy first-degree relatives and 227 healthy controls without a family history of autoimmune disease (all females) were examined twice annually over more than 10 years.Primary and secondary outcome measuresThe following parameters were investigated: type, duration and frequency of infections, bacterial colonisation and serum levels of IgG to bacteria, serum levels of total Ig, plasma cytokine levels, granulocyte reactive oxygen species production, lysozyme activity and phagocytosis.ResultsThere were no significant differences in infection rate between healthy controls (median 14 days/year) and RA patients (13). However, infection rates were higher (p<0.001) in healthy relatives (53) and early stage patients (62), which groups also showed heavy bacterial skin colonisation. In contrast, late stage patients had fewer infection days (12; p<0.001) than healthy controls, although bacterial colonisation was still heavy. Phagocyte function and antibacterial antibody generation, together with compensatory cytokine production, were observed to be subnormal in the healthy relatives as well as in RA patients.ConclusionsWe observed a marked increase in overall infections at the time of RA onset, and signs of a defective antibacterial defence mechanism, contrasting with fewer infections in the late RA stage. It can be speculated that frequent early infections initiate a compensatory immune hyper-reactivity which reduces the infection load while stimulating the development of RA in predisposed individuals.
Prevalence and risk factors for allergic rhinitis in bakers in Douala, Cameroon
Authors: Mbatchou Ngahane Bertrand Hugo , Afane Ze Emmanuel , Nde Francis , Ngomo Eliane , Mapoure Njankouo Yacouba , Njock Louis Richard 
Published: September 2014

ObjectiveTo determine the prevalence and risk factors of allergic rhinitis among bakers in Douala.DesignA cross-sectional study; the logistic regression model was use to find the risk factors of allergic rhinitis.SettingThe study was conducted in 42 bakeries randomly selected among a total of 151 bakeries in the city of Douala.ParticipantsAll bakers who consented to participate in the study between 1 May and 31 July 2013.Outcome measuresAllergic rhinitis was the outcome of interest. It was defined as the presence of the following symptoms: itchy nose, rhinorrhea, nasal obstruction and sneezing.ResultsDuring the study period, a total of 273 bakers were invited and 229 finally agreed to participate in this study. Males were the most represented gender with 222 (96.9%) participants. The mean age of the participants was 36.29±8.9 years. Smoking was found in 55 participants (24.5%). The symptoms of allergic rhinitis were observed in 24.5% of participants. Work related nasal symptoms were present in 15% of participants. Sensitisation to wheat flour and α-amylase was found in 16.6% and 8.3% of participants, respectively. The Prick test was positive for mites in 12.2% of participants. After multivariate analysis, sensitisation to flour (OR 3.95, 95% CI 1.85 to 8.47) and storage mites (OR 3.44, 95% CI 1.45 to 8.18) were the factors independently associated with symptoms of allergic rhinitis.ConclusionsAllergic rhinitis is frequent among bakers in Cameroon. Implementation of preventive measures against inhalation of airborne allergens in bakeries and clinical monitoring of bakers sensitised to wheat flour and mites could help to reduce the prevalence of allergic rhinitis among bakers.
TheHutongeffect: informal social control and community psychology in Beijing
Authors: Emery Clifton R , Wu Shali , Raghavan Ramesh 
Published: September 2014

BackgroundNearly 2.4 million Beijing residents experience intimate partner violence (IPV) annually. Of these 2.4 million, over 800 000 are injured by IPV; more than 300 000 are injured badly enough to require medical attention. Informal social control exerted by neighbours in communities with high levels of family–community integration (like those made up of residents of traditional courtyard house-and-alley Beijing neighbourhoods called ‘Hutongs’) may protect against IPV injury compared with apartment dwellers.MethodsWe tested the protective effects of informal social control and Hutong residence in a randomly selected, three-stage cluster sample of Beijing families reporting IPV. Informal social control of IPV (ISC_IPV) was measured using two 7-question Likert scales developed by the first author. Interviewers were given detailed instructions on how to classify neighbourhoods as Hutong-style or not. We used a Sobel test to examine whether the Hutong effect was mediated by informal social control. The initial sample was of 506 families. Analyses were carried out on 113 families who reported any IPV in the last year.ResultsRandom effects regression models showed that both acts of informal social control and Hutong residence were associated with less IPV injury. However, the protective finding for Hutong residence was not explained by informal social control, collective efficacy, characteristics of the IPV or demographic characteristics of respondents and households.ConclusionsThe unique protective association with Hutong residence suggests that the benefits of community life remain insufficiently theorised and understood.
Predictive significance of absolute lymphocyte count and morphology in adults with a new onset peripheral blood lymphocytosis
Authors: Sun Ping , Kowalski Emilia M , Cheng Calvino K , Shawwa Allam , Liwski Robert S , Juskevicius Ridas 
Published: September 2014

AimsLymphocytosis is commonly encountered in the haematology laboratory. Evaluation of blood films is an important screening tool for differentiating between reactive and malignant processes. The optimal lymphocyte number to trigger morphological evaluation of the smear has not been well defined in the literature. Likewise, the significance of lymphocyte morphology has not been well studied and there are no consensus guidelines or follow-up recommendations available. We attempt to evaluate the significance of lymphocyte morphology and to define the best possible cut-off value of absolute lymphocyte count for morphology review.Methods71 adult patients with newly detected lymphocytosis of 5.0×109/L or more were categorised to either a reactive process or a lymphoproliferative disorder. We performed statistical analysis and morphology review to compare the difference in age, gender, lymphocyte count and morphological features between the two groups. Receiver operating characteristic analysis was performed to determine an optimal lymphocyte number to trigger morphology review.ResultsLymphoproliferative disorders are associated with advanced age and higher lymphocyte count. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of lymphocyte morphology as a screening test were 0.9, 0.59, 0.60, 0.58 and 0.71, respectively. The optimal cut-off of lymphocyte number for morphology review was found to be close to 7×109/L.ConclusionsWe found a moderate interobserver agreement for the morphological assessment. ‘Reactive’ morphology was very predictive of a reactive process, but ‘malignant’ morphology was a poor predictor of a lymphoproliferative disorder.
Modeling Contact Guidance and Invasion by Cancer Cells
Authors: Sander Leonard M. 
Published: September 2014

Abstract
The first step in the spread of cancer is invasion by malignant cells of the normal tissue surrounding a tumor. There is considerable evidence both in vitro and in vivo that mechanical interactions with the tissue, in particular with the biopolymer network that makes up the extracellular matrix (ECM), are important factors in invasion. The interactions take two forms: (i) contractile cells on the surface of the tumor act on the nearby ECM and remodel it; in some cases, they align the fibers of the biopolymers; (ii) the aligned fibers can enhance invasion via contact guidance, the tendency of motile cells to follow alignment. Here, we give evidence, mainly for in vitro systems, that both effects are important. We discuss how alignment occurs in biopolymers such as collagen-I (a major component of the ECM). We propose a modeling framework for computing alignment and propose phenomenologic models for contact guidance.
See all articles in this Cancer Research section, “Physics in Cancer Research.”
Cancer Res; 74(17); 4588–96. ©2014 AACR.
Therapies with Diverse Mechanisms of Action Kill Cells by a Similar Exponential Process in Advanced Cancers
Authors: Blagoev Krastan B. , Wilkerson Julia , Stein Wilfred D. , Yang James , Bates Susan E. , Fojo Tito 
Published: September 2014

Abstract
Successful cancer treatments are generally defined as those that decrease tumor quantity. In many cases, this decrease occurs exponentially, with deviations from a strict exponential being attributed to a growing fraction of drug-resistant cells. Deviations from an exponential decrease in tumor quantity can also be expected if drugs have a nonuniform spatial distribution inside the tumor, for example, because of interstitial pressure inside the tumor. Here, we examine theoretically different models of cell killing and analyze data from clinical trials based on these models. We show that the best description of clinical outcomes is by first-order kinetics with exponential decrease of tumor quantity. We analyzed the total tumor quantity in a diverse group of clinical trials with various cancers during the administration of different classes of anticancer agents and in all cases observed that the models that best fit the data describe the decrease of the sensitive tumor fraction exponentially. The exponential decrease suggests that all drug-sensitive cancer cells have a single rate-limiting step on the path to cell death. If there are intermediate steps in the path to cell death, they are not rate limiting in the observational time scale utilized in clinical trials—tumor restaging at 6- to 8-week intervals. On shorter time scales, there might be intermediate steps, but the rate-limiting step is the same. Our analysis, thus, points to a common pathway to cell death for cancer cells in patients.
See all articles in this Cancer Research section, “Physics in Cancer Research.”
Cancer Res; 74(17); 4653–62. ©2014 AACR.
New Strategies in Personalized Medicine for Solid Tumors: Molecular Markers and Clinical Trial Designs
Authors: Jürgensmeier Juliane M. , Eder Joseph P. , Herbst Roy S. 
Published: September 2014

Abstract
The delineation of signaling pathways to understand tumor biology combined with the rapid development of technologies that allow broad molecular profiling and data analysis has led to a new era of personalized medicine in oncology. Many academic institutions now routinely profile patients and discuss their cases in meetings of personalized medicine tumor boards before making treatment recommendations. Clinical trials initiated by pharmaceutical companies often require specific markers for enrollment or at least explore multiple options for future markers. In addition to the still small number of targeted agents that are approved for the therapy of patients with histological and molecularly defined tumors, a broad range of novel targeted agents in development are undergoing clinical studies with companion profiling to determine the best-responding patient population. Although the present focus of profiling lies in genetic analyses, additional tests of RNA, protein, and immune parameters are being developed and incorporated in clinical research, and these methods are likely to contribute significantly to future patient selection and treatment approaches. As the advances in tumor biology and human genetics have identified promising tumor targets, the ongoing clinical evaluation of novel agents will now need to show if the promise can be translated into benefit for patients. Clin Cancer Res; 20(17); 4425–35. ©2014 AACR.