bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of unacceptable HLA antigen mismatches in kidney transplant recipients: recommendations of the German Society for Immunogenetics
Authors: Süsal C. , Seidl C. , Schönemann C. , Heinemann F. M. , Kauke T. , Gombos P. , Kelsch R. , Arns W. , Bauerfeind U. , Hallensleben M. , Hauser I. A. , Einecke G. , Blasczyk R. 
Published: October 2015

AbstractOne of the major tasks of histocompatibility and immunogenetics laboratories is the pretransplant determination of unacceptable antigen mismatches (UAM) in kidney transplant recipients. In this procedure, human leucocyte antigen (HLA) specificities are defined against which the patient has circulating alloantibodies that are expected to harm the transplanted organ. Using the information on UAM and the potential donor's complete HLA typing, prediction of the crossmatch result, the so called ‘virtual crossmatch’, is possible. Currently, the laboratories are using different algorithms for the determination of UAM, and depending on the algorithm, more or fewer organ offers are excluded for patients with a similar antibody profile. In order to bring homogeneity into the allocation of organs to immunized patients in Germany, the German Society for Immunogenetics established, on the basis of current knowledge, recommendations for the determination of UAM. The UAM recommendations, which are thought to serve as a common tool for responsible physicians at different transplant centers, contain technical issues that need to be considered and are individualized for sensitized patients with a high or intermediate risk of antibody‐mediated rejection. The present review contains these recommendations and puts them into perspective to current international practice.
Altitude and regional gradients in chronic kidney disease prevalence in Costa Rica: Data from the Costa Rican Longevity and Healthy Aging Study
Authors: Harhay Meera N. , Harhay Michael O. , Coto‐Yglesias Fernando , Rosero Bixby Luis 
Published: October 2015

AbstractObjectivesRecent studies in Central America indicate that mortality attributable to chronic kidney disease (CKD) is rising rapidly. We sought to determine the prevalence and regional variation of CKD and the relationship of biologic and socio‐economic factors to CKD risk in the older‐adult population of Costa Rica.MethodsWe used data from the Costa Rican Longevity and Health Aging Study (CRELES). The cohort was comprised of 2657 adults born before 1946 in Costa Rica, chosen through a sampling algorithm to represent the national population of Costa Ricans >60 years of age. Participants answered questionnaire data and completed laboratory testing. The primary outcome of this study was CKD, defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2.ResultsThe estimated prevalence of CKD for older Costa Ricans was 20% (95% CI 18.5–21.9%). In multivariable logistic regression, older age (adjusted odds ratio [aOR] 1.08 per year, 95% CI 1.07–1.10, P < 0.001) was independently associated with CKD. For every 200 m above sea level of residence, subjects' odds of CKD increased 26% (aOR 1.26 95% CI 1.15–1.38, P < 0.001). There was large regional variation in adjusted CKD prevalence, highest in Limon (40%, 95% CI 30–50%) and Guanacaste (36%, 95% CI 26–46%) provinces. Regional and altitude effects remained robust after adjustment for socio‐economic status.ConclusionsWe observed large regional and altitude‐related variations in CKD prevalence in Costa Rica, not explained by the distribution of traditional CKD risk factors. More studies are needed to explore the potential association of geographic and environmental exposures with the risk of CKD.
Can Nomenclature for the Body be Explained by Embodiment Theories?
Authors: Majid Asifa , van Staden Miriam 
Published: October 2015

AbstractAccording to widespread opinion, the meaning of body part terms is determined by salient discontinuities in the visual image; such that hands, feet, arms, and legs, are natural parts. If so, one would expect these parts to have distinct names which correspond in meaning across languages. To test this proposal, we compared three unrelated languages—Dutch, Japanese, and Indonesian—and found both naming systems and boundaries of even basic body part terms display variation across languages. Bottom‐up cues alone cannot explain natural language semantic systems; there simply is not a one‐to‐one mapping of the body semantic system to the body structural description. Although body parts are flexibly construed across languages, body parts semantics are, nevertheless, constrained by non‐linguistic representations in the body structural description, suggesting these are necessary, although not sufficient, in accounting for aspects of the body lexicon.
Chloroplastic thioredoxin m functions as a major regulator of Calvin cycle enzymes during photosynthesis in vivo
Authors: Okegawa Yuki , Motohashi Ken 
Published: October 2015

SummaryThioredoxins (Trxs) regulate the activity of various chloroplastic proteins in a light‐dependent manner. Five types of Trxs function in different physiological processes in the chloroplast of Arabidopsis thaliana. Previous in vitro experiments have suggested that the f‐type Trx (Trx f) is the main redox regulator of chloroplast enzymes, including Calvin cycle enzymes. To investigate the in vivo contribution of each Trx isoform to the redox regulatory system, we first quantified the protein concentration of each Trx isoform in the chloroplast stroma. The m‐type Trx (Trx m), which consists of four isoforms, was the most abundant type. Next, we analyzed several Arabidopsis Trx‐m‐deficient mutants to elucidate the physiological role of Trx m in vivo. Deficiency of Trx m impaired plant growth and decreased the CO2 assimilation rate. We also determined the redox state of Trx target enzymes to examine their photo‐reduction, which is essential for enzyme activation. In the Trx‐m‐deficient mutants, the reduction level of fructose‐1,6‐bisphosphatase and sedoheptulose‐1,7‐bisphosphatase was lower than that in the wild type. Inconsistently with the historical view, our in vivo study suggested that Trx m plays a more important role than Trx f in the activation of Calvin cycle enzymes.
Jasmonate signalling drives time‐of‐day differences in susceptibility of Arabidopsis to the fungal pathogen Botrytis cinerea
Authors: Ingle Robert A. , Stoker Claire , Stone Wendy , Adams Nicolette , Smith Rob , Grant Murray , Carré Isabelle , Roden Laura C. , Denby Katherine J. 
Published: October 2015

SummaryThe circadian clock, an internal time‐keeping mechanism, allows plants to anticipate regular changes in the environment, such as light and dark, and biotic challenges such as pathogens and herbivores. Here, we demonstrate that the plant circadian clock influences susceptibility to the necrotrophic fungal pathogen, Botrytis cinerea. Arabidopsis plants show differential susceptibility to B. cinerea depending on the time of day of inoculation. Decreased susceptibility after inoculation at dawn compared with night persists under constant light conditions and is disrupted in dysfunctional clock mutants, demonstrating the role of the plant clock in driving time‐of‐day susceptibility to B. cinerea. The decreased susceptibility to B. cinerea following inoculation at subjective dawn was associated with faster transcriptional reprogramming of the defence response with gating of infection‐responsive genes apparent. Direct target genes of core clock regulators were enriched among the transcription factors that responded more rapidly to infection at subjective dawn than subjective night, suggesting an influence of the clock on the defence‐signalling network. In addition, jasmonate signalling plays a crucial role in the rhythmic susceptibility of Arabidopsis to B. cinerea with the enhanced susceptibility to this pathogen at subjective night lost in a jaz6 mutant.
A novel bioreactor and culture method drives high yields of platelets from stem cells
Authors: Avanzi Mauro P. , Oluwadara Oluwasijibomi E. , Cushing Melissa M. , Mitchell Maxwell L. , Fischer Stephen , Mitchell W. Beau 
Published: October 2015

BACKGROUNDPlatelet (PLT) transfusion is the primary treatment for thrombocytopenia. PLTs are obtained exclusively from volunteer donors, and the PLT product has only a 5‐day shelf life, which can limit supply and result in PLT shortages. PLTs derived from stem cells could help to fill this clinical need. However, current culture methods yield far too few PLTs for clinical application. To address this need, a defined, serum‐free culture method was designed using a novel bioreactor to increase the yield of PLTs from stem cell‐derived megakaryocytes.STUDY DESIGN AND METHODSCD34 cells isolated from umbilical cord blood were expanded with a variety of reagents and on a nanofiber membrane using serum‐free medium. These cells were then differentiated into megakaryocytic lineage by culturing with thrombopoietin and stem cell factor in serum‐free conditions. Polyploidy was induced by addition of Rho kinase inhibitor or actin polymerization inhibitor to the CD41 cells. A novel bioreactor was developed that recapitulated aspects of the marrow vascular niche. Polyploid megakaryocytes that were subjected to flow in the bioreactor extended proPLTs and shed PLTs, as confirmed by light microscopy, fluorescence imaging, and flow cytometry.RESULTSCD34 cells were expanded 100‐fold. CD41 cells were expanded 100‐fold. Up to 100 PLTs per input megakaryocyte were produced from the bioreactor, for an overall yield of 106 PLTs per input CD34 cell. The PLTs externalized P‐selectin after activation.DISCUSSIONFunctional PLTs can be produced ex vivo on a clinically relevant scale using serum‐free culture conditions with a novel stepwise approach and an innovative bioreactor.
Pseudomonas aeruginosa Triggers Macrophage Autophagy To Escape Intracellular Killing by Activation of the NLRP3 Inflammasome
Authors: Deng Qiuchan , Wang Yi , Zhang Yuanqing , Li Meiyu , Li Dandan , Huang Xi , Wu Yongjian , Pu Jieying , Wu Minhao 
Published: October 2015

ABSTRACT

Assembly of the inflammasome has recently been identified to be a critical event in the initiation of inflammation. However, its role in bacterial killing remains unclear. Our study demonstrates that
Pseudomonas aeruginosa
infection induces the assembly of the NLRP3 inflammasome and the sequential secretion of caspase1 and interleukin-1β (IL-1β) in human macrophages. More importantly, activation of the NLRP3 inflammasome reduces the killing of
P. aeruginosa
in human macrophages, without affecting the generation of antimicrobial peptides, reactive oxygen species, and nitric oxide. In addition, our results demonstrate that
P. aeruginosa
infection increases the amount of the LC3-II protein and triggers the formation of autophagosomes in human macrophages. The
P. aeruginosa
-induced autophagy was enhanced by overexpression of NLRP3, ASC, or caspase1 but was reduced by knockdown of these core molecules of the NLRP3 inflammasome. Treatment with IL-1β enhanced autophagy in human macrophages. More importantly, IL-1β decreased the macrophage-mediated killing of
P. aeruginosa
, whereas knockdown of ATG7 or Beclin1 restored the IL-1β-mediated suppression of bacterial killing. Collectively, our study explores a novel mechanism employed by
P. aeruginosa
to escape from phagocyte killing and may provide a better understanding of the interaction between
P. aeruginosa
and host immune cells, including macrophages.
Comparative Evaluation of AmpliVue HSV 1+2 Assay with ELVIS Culture for Detecting Herpes Simplex Virus 1 (HSV-1) and HSV-2 in Clinical Specimens
Authors: Granato Paul A. , Alkins Brenda R. , Yen-Lieberman Belinda , Greene Wallace H. , Connolly Jessica , Buchan Blake W. , Ledeboer Nathan A. 
Published: October 2015

ABSTRACT

The AmpliVue HSV 1+2 assay was compared to the ELVIS HSV ID and D
3
Typing Culture System for the qualitative detection and differentiation of herpes simplex virus 1 (HSV-1) and HSV-2 DNA in 1,351 cutaneous and mucocutaneous specimens. Compared to ELVIS, AmpliVue had sensitivities of 95.7 and 97.6% for detecting HSV-1 and HSV-2, respectively. Following arbitration of discordant results by an independent molecular method, the AmpliVue assay had a resolved sensitivity and specificity of 99.2 and 99.7%, respectively, for both HSV-1 and HSV-2, whereas ELVIS had a resolved sensitivity of 87.1% for HSV-1 and 84.5% for HSV-2.
Impact of HIV Infection Status on Interpretation of Quantitative PCR for Detection of Pneumocystis jirovecii
Authors: Louis M. , Guitard J. , Jodar M. , Ancelle T. , Magne D. , Lascols O. , Hennequin C. 
Published: October 2015

ABSTRACT

Quantitative PCR (qPCR) is now a key diagnostic tool for
Pneumocystis
pneumonia. However, cutoffs to distinguish between infected and colonized patients according to their HIV status have not yet been determined. According to clinical, radiological, and biological data, we retrospectively classified bronchoalveolar lavage (BAL) samples subjected to qPCR over a 3-year period into four categories, i.e., definite PCP, probable PCP,
Pneumocystis
colonization, and no infection. Fungal burden was then analyzed according to the HIV status of the patients. Among 1,212 episodes of pneumonia screened in immunocompromised patients, 52 and 27 HIV-positive patients were diagnosed with a definite and probable PCP, whereas 4 and 22 HIV-negative patients had definite and probable PCP, respectively. Among patients with definite or a probable PCP, HIV-negative patients had a significantly lower burden than HIV-positive patients (
P
< 10
−4
). In both groups, the median fungal burden was significantly higher in patients with definite PCP than in colonized patients. A single cutoff at 1.5 × 10
4
copies/ml allowed to differentiate colonized and infected HIV-positive patients with 100% sensitivity and specificity. In HIV-negative patients, cutoff values of 2.87 × 10
4
and 3.39 × 10
3
copies/ml resulted in 100% specificity and sensitivity, respectively. Using cutoffs determined for the whole population would have led us to set aside the diagnosis of PCP in 9 HIV-negative patients with definite or probable PCP. qPCR appeared to be the most sensitive test to detect
Pneumocystis
in BAL samples. However, because of lower inocula in HIV-negative patients, different cutoffs must be used according to the HIV status to differentiate between colonized and infected patients.
Commentary: Continuing Challenges for the Clinical Laboratory for Detection of Carbapenem-Resistant Enterobacteriaceae
Authors: Humphries Romney M. , McKinnell James A. 
Published: October 2015

ABSTRACT

Detecting carbapenem-resistant
Enterobacteriaceae
(CRE) can be difficult. In particular, the absence of FDA-cleared automated antimicrobial susceptibility test (AST) devices that use revised Clinical and Laboratory Standards Institute (CLSI) carbapenem breakpoints for
Enterobacteriaceae
and the lack of active surveillance tests hamper the clinical laboratory. In this issue of the
Journal of Clinical Microbiology
, Lau and colleagues (A. F. Lau, G. A. Fahle, M. A. Kemp, A. N. Jassem, J. P. Dekker, and K. M. Frank, J Clin Microbiol 53:3729–3737, 2015,
http://dx.doi.org/10.1128/JCM.01921-15
) evaluate the performance of a research-use-only PCR for the detection of CRE in rectal surveillance specimens.
Duck Interferon-Inducible Transmembrane Protein 3 Mediates Restriction of Influenza Viruses
Authors: Blyth Graham A. D. , Chan Wing Fuk , Webster Robert G. , Magor Katharine E. 
Published: October 2015

ABSTRACT

Interferon-inducible transmembrane proteins (IFITMs) can restrict the entry of a wide range of viruses. IFITM3 localizes to endosomes and can potently restrict the replication of influenza A viruses (IAV) and several other viruses that also enter host cells through the endocytic pathway. Here, we investigate whether IFITMs are involved in protection in ducks, the natural host of influenza virus. We identify and sequence duck
IFITM1
,
IFITM2
,
IFITM3
, and
IFITM5
. Using quantitative PCR (qPCR), we demonstrate the upregulation of these genes in lung tissue in response to highly pathogenic IAV infection by 400-fold, 30-fold, 30-fold, and 5-fold, respectively. We express each IFITM in chicken DF-1 cells and show duck IFITM1 localizes to the cell surface, while IFITM3 localizes to LAMP1-containing compartments. DF-1 cells stably expressing duck IFITM3 (but not IFITM1 or IFITM2) show increased restriction of replication of H1N1, H6N2, and H11N9 IAV strains but not vesicular stomatitis virus. Although duck and human IFITM3 share only 38% identity, critical residues for viral restriction are conserved. We generate chimeric and mutant IFITM3 proteins and show duck IFITM3 does not require its N-terminal domain for endosomal localization or antiviral function; however, this N-terminal end confers endosomal localization and antiviral function on IFITM1. In contrast to mammalian IFITM3, the conserved YXXθ endocytosis signal sequence in the N-terminal domain of duck IFITM3 is not essential for correct endosomal localization. Despite significant structural and amino acid divergence, presumably due to host-virus coevolution, duck IFITM3 is functional against IAV.

IMPORTANCE
Immune IFITM genes are poorly conserved across species, suggesting that selective pressure from host-specific viruses has driven this divergence. We wondered whether coevolution between viruses and their natural host would result in the evasion of IFITM restriction. Ducks are the natural host of avian influenza A viruses and display few or no disease symptoms upon infection with most strains, including highly pathogenic avian influenza. We have characterized the duck IFITM locus and identified IFITM3 as an important restrictor of several influenza A viruses, including avian strains. With only 38% amino acid identity to human IFITM3, duck IFITM3 possesses antiviral function against influenza virus. Thus, despite long coevolution of virus and host effectors in the natural host, influenza virus evasion of IFITM3 restriction in ducks is not apparent.
Hepatitis C Virus NS4B Can Suppress STING Accumulation To Evade Innate Immune Responses
Authors: Yi Guanghui , Wen Yahong , Shu Chang , Han Qingxia , Konan Kouacou V. , Li Pingwei , Kao C. Cheng 
Published: October 2015

ABSTRACT
The cyclic dinucleotide 2′,3′-cGAMP can bind the adaptor protein STING (stimulator of interferon [IFN] genes) to activate the production of type I IFNs and proinflammatory cytokines. We found that cGAMP added to the culture medium could suppress the replication of the hepatitis C virus (HCV) genotype 1b strain Con1 subgenomic replicon in human hepatoma cells. Knockdown of STING expression diminished the inhibitory effect on replicon replication, while overexpression of STING enhanced the inhibitory effects of cGAMP. The addition of cGAMP into 1b/Con1 replicon cells significantly increased the expression of type I IFNs and antiviral interferon-stimulated genes. Unexpectedly, replication of the genotype 2a JFH1 replicon and infectious JFH1 virus was less sensitive to the inhibitory effect of cGAMP than was that of 1b/Con1 replicon. Using chimeric replicons, 2a NS4B was identified to confer resistance to cGAMP. Transient expression of 2a NS4B resulted in a pronounced inhibitory effect on STING-mediated beta IFN (IFN-β) reporter activation compared to that of 1b NS4B. 2a NS4B was found to suppress STING accumulation in a dose-dependent manner. The predicted transmembrane domain of 2a NS4B was required to inhibit STING accumulation. These results demonstrate a novel genotype-specific inhibition of the STING-mediated host antiviral immune response.

IMPORTANCE
The cyclic dinucleotide cGAMP was found to potently inhibit the replication of HCV genotype 1b Con1 replicon but was less effective for the 2a/JFH1 replicon and infectious JFH1 virus. The predicted transmembrane domain in 2a NS4B was shown to be responsible for the decreased sensitivity to cGAMP. The N terminus of NS4B has been reported to suppress STING-mediated signaling by disrupting the interaction of STING and TBK1 and/or MAVS. We show that 2a/JFH1 NS4B has an additional mechanism to evade STING signaling through suppressing STING accumulation.
Comparative Efficacy of Monoclonal Antibodies That Bind to Different Epitopes of the 2009 Pandemic H1N1 Influenza Virus Neuraminidase
Authors: Jiang Lianlian , Fantoni Giovanna , Couzens Laura , Gao Jin , Plant Ewan , Ye Zhiping , Eichelberger Maryna C. , Wan Hongquan 
Published: October 2015

ABSTRACT

Antibodies against the neuraminidase (NA) of influenza virus correlate with resistance against disease, but the effectiveness of antibodies against different NA epitopes has not been compared. In the present study, we evaluated the
in vitro
and
in vivo
efficacies of four monoclonal antibodies (MAbs): HF5 and CD6, which are specific to two different epitopes in the NA of 2009 pandemic H1N1 (pH1N1) virus, and 4E9 and 1H5, which are specific to a conserved epitope in the NA of both H1N1 and H5N1 viruses. In the
in vitro
assays, HF5 and CD6 inhibited virus spread and growth more effectively than 4E9 and 1H5, with HF5 being the most effective inhibitor. When administered prophylactically at 5 mg/kg of body weight, HF5 and CD6 protected ∼90 to 100% of DBA/2 mice against lethal wild-type pH1N1 virus challenge; however, at a lower dose (1 mg/kg), HF5 protected ∼90% of mice, whereas CD6 protected only 25% of mice. 4E9 and 1H5 were less effective than HF5 and CD6, as indicated by the partial protection achieved even at doses as high as 15 mg/kg. When administered therapeutically, HF5 protected a greater proportion of mice against lethal pH1N1 challenge than CD6. However, HF5 quickly selected pH1N1 virus escape mutants in both prophylactic and therapeutic treatments, while CD6 did not. Our findings confirm the important role of NA-specific antibodies in immunity to influenza virus and provide insight into the properties of NA antibodies that may serve as good candidates for therapeutics against influenza.

IMPORTANCE
Neuraminidase (NA) is one of the major surface proteins of influenza virus, serving as an important target for antivirals and therapeutic antibodies. The impact of NA-specific antibodies on NA activity and virus replication is likely to depend on where the antibody binds. Using
in vitro
assays and the mouse model, we compared the inhibitory/protective efficacy of four mouse monoclonal antibodies (MAbs) that bind to different sites within the 2009 pandemic H1N1 (pH1N1) virus NA. The ability of each MAb to protect mice against lethal pH1N1 infection corresponded to its ability to inhibit NA activity
in vitro
; however, the MAb that was the most effective inhibitor of NA activity selected pH1N1 escape variants
in vivo
. One of the tested MAbs, which binds to a conserved region in the NA of pH1N1 virus, inhibited NA activity but did not result in escape variants, highlighting its suitability for development as a therapeutic agent.