bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do pathogens reduce genetic diversity of their hosts? Variable effects of sylvatic plague in black‐tailed prairie dogs
Authors: Sackett Loren C. , Collinge Sharon K. , Martin Andrew P. 
Published: March 2013

AbstractIntroduced diseases can cause dramatic declines in—and even the loss of—natural populations. Extirpations may be followed by low recolonization rates, leading to inbreeding and a loss of genetic variation, with consequences on population viability. Conversely, extirpations may create vacant habitat patches that individuals from multiple source populations can colonize, potentially leading to an influx of variation. We tested these alternative hypotheses by sampling 15 colonies in a prairie dog metapopulation during 7 years that encompassed an outbreak of sylvatic plague, providing the opportunity to monitor genetic diversity before, during and after the outbreak. Analysis of nine microsatellite loci revealed that within the metapopulation, there was no change in diversity. However, within extirpated colonies, patterns varied: In half of the colonies, allelic richness after recovery was less than the preplague conditions, and in the other half, richness was greater than the preplague conditions. Finally, analysis of variation within individuals revealed that prairie dogs present in recolonized colonies had higher heterozygosity than those present before plague. We confirmed plague survivorship in six founders; these individuals had significantly higher heterozygosity than expected by chance. Collectively, our results suggest that high immigration rates can maintain genetic variation at a regional scale despite simultaneous extirpations in spatially proximate populations. Thus, virulent diseases may increase genetic diversity of host populations by creating vacant habitats that allow an influx of genetic diversity. Furthermore, even highly virulent diseases may not eliminate individuals randomly; rather, they may selectively remove the most inbred individuals.
Differential effects of CXCR4‐CXCL12‐ and CXCR7‐CXCL12‐mediated immune reactions on murine P0106–125‐induced experimental autoimmune neuritis
Authors: Brunn A. , Utermöhlen O. , Mihelcic M. , Sánchez‐Ruiz M. , Carstov M. , Blau T. , Ustinova I. , Penfold M. , Montesinos‐Rongen M. , Deckert M. 
Published: March 2013

AimThe role of chemokines and their receptors, which regulate trafficking and homing of leucocytes to inflamed organs in human or murine autoimmune neuritis, has not yet been elucidated in detail, Therefore, the role of the chemokine receptors CXCR4 and CXCR7 and their ligand CXCL12 was studied in autoimmune‐mediated inflammation of the peripheral nervous system.MethodsCXCL12/CXCR4 and/or CXCL12/CXCR7 interactions were specifically inhibited by the compounds AMD3100 or CCX771, respectively, in experimental autoimmune neuritis (EAN) of C57BL/6J mice immunized with P0106–125 peptide.ResultsDisease activity was significantly suppressed by blocking CXCR7 while antagonization of CXCR4 enhanced disease activity. Enhanced disease activity was accompanied by significantly increased transcription of IFN‐γ, IL‐12 and TNF‐α mRNA in regional lymph nodes and spleen as well as by increased serum levels of IFN‐γ. Furthermore, by blocking CXCR4, expression of the cell adhesion molecules ICAM‐1 and VCAM‐1 was upregulated on vascular endothelial cells of the sciatic nerve, which coincided with significantly increased infiltration of the sciatic nerve by CD4+ T cells and macrophages. Remarkably, combined antagonization of both CXCR4 and CXCR7 significantly suppressed disease activity. This was accompanied by increased frequencies of activated and highly IFN‐γ‐expressing, P0106–125‐specific T cells in regional lymph nodes and spleen; however, these cells were unable to infiltrate the sciatic nerve.ConclusionThese data suggest differential and hierarchically ordered roles for CXCR4/CXCL12‐ vs. CXCR7/CXCL12‐dependent effects during EAN: CXCR7/CXCL12 interaction is a gatekeeper for pathogenic cells, regardless of their CXCR4/CXCL12‐dependent state of activation.
Overexpression of autophagic proteins in the skeletal muscle of sporadic inclusion body myositis
Authors: Girolamo F. , Lia A. , Amati A. , Strippoli M. , Coppola C. , Virgintino D. , Roncali L. , Toscano A. , Serlenga L. , Trojano M. 
Published: March 2013

AimsSporadic inclusion body myositis (s‐IBM) is characterized by rimmed vacuole formation and misfolded protein accumulation. Intracellular protein aggregates are cleared by autophagy. When autophagy is blocked aggregates accumulate, resulting in abnormal rimmed vacuole formation. This study investigated the autophagy–lysosome pathway contribution to rimmed vacuole accumulation.MethodsAutophagy was studied in muscle biopsy specimens obtained from eleven s‐IBM patients, one suspected hereditary IBM patient, nine patients with other inflammatory myopathies and nine non‐myopathic patients as controls. The analysis employed morphometric methods applied to immunohistochemistry using the endosome marker Clathrin, essential proteins of the autophagic cascade such as AuTophaGy‐related protein ATG5, splicing variants of microtubule‐associated protein light chain 3a (LC3a) and LC3b, compared with Beclin 1, the major autophagy regulator of both the initiation phase and late endosome/lysosome fusion of the autophagy–lysosome pathway.ResultsIn muscle biopsies of s‐IBM patients, an increased expression of Clathrin, ATG5, LC3a, LC3b and Beclin 1 was shown. Moreover, the inflammatory components of the disease, essentially lymphocytes, were preferentially distributed around the Beclin 1+ myofibres. These affected myofibres also showed a moderate sarcoplasmic accumulation of SMI‐31+ phospho‐tau paired helical filaments.ConclusionThe overexpression of autophagy markers linked to the decreased clearance of misfolded proteins, including SMI‐31, and rimmed vacuoles accumulation may exhaust cellular resources and lead to cell death.
Calculation of power and field of view of keratoprostheses
Authors: Langenbucher Achim , Szentmáry Nóra , Speck Alexis , Seitz Berthold , Eppig Timo 
Published: March 2013

AbstractPurposeTo demonstrate a mathematical algorithm for calculating the refractive power of keratoprostheses and to estimate vignetting effects.MethodsA paraxial calculation scheme based on vergence transformation is developed for determination of the front surface radius or front surface refractive power of a Boston type I or II keratoprosthesis based on the design data of the manufacturer. A concept for derivation of lateral magnification (ratio of image size to slope of the incident ray) is presented based on 2 × 2 matrix representation of the eye. For estimation of vignetting effects, numerical ray tracing was used and the maximum half field angle and half luminance half field angle was extracted.ResultsSimulation calculations were performed in MATLAB. The front surface radius or refractive power is given in explicit form as a function of axial length, target refraction, as well as the principal design data of the keratoprosthesis such as posterior refractive power, length, or refractive index. With variation of the back surface radius it was shown that lateral magnification can be modulated e.g. to match the magnification of the fellow eye. The Boston type I does not restrict the field angle substantially, whereas type II shows significant vignetting effects.ConclusionWe present a strategy on the calculation of keratoprostheses and variation of the design (e.g. back surface curvature) to help to avoid aniseikonia in case of binocular vision (e.g. one phakic eye and one with keratoprosthesis).
Reduction in vasovagal reaction rate in young first‐time blood donors by collecting 350 mL rather than 450 mL
Authors: Wong H.K. , Lee C.K. , Leung J.N. , Lee I.Y. , Lin C.K. 
Published: March 2013

BackgroundThere is a paucity of studies on the magnitude of reduction of vasovagal reaction by reduced collection volume. This study was thus conducted to determine the difference in reaction rates between two collection volumes among the young first‐time donors who are at particular risk of reaction.Study Design and MethodsThis retrospective study analyzed 38,436 whole blood donations made by young (aged 16 to 18 years) first‐time donors. The effect of collection volume on vasovagal reaction was compared among different weight subgroups for both sexes by chi‐square test.ResultsFor females in all weight subgroups and two of the male lower‐weight subgroups, the reduction percentages ranged from 35% to 58% (p < 0.05). It was also noted that, among the females, a higher weight was associated with a higher percent reduction in the reaction rate.ConclusionWith reduced collection volume, this study detected large and significant reduction in reaction rates among all females, as well as lower‐weight males.
Role of donor and recipient sex in platelet transfusion
Authors: Stern Martin , Infanti Laura , O'Meara Alix , Sigle Jörg , Buser Andreas 
Published: March 2013

BackgroundH‐Y proteins are ubiquitously expressed Y chromosome‐encoded minor histocompatibility antigens, which are relevant in the transplantation of hematopoietic stem cells (HSCT) and solid organs. No studies have so far analyzed whether H‐Y incompatibility influences the outcome of platelet (PLT) transfusion.Study Design and MethodsWe studied the effect of donor and recipient sex on outcome of 9038 single‐donor PLT transfusions.ResultsUsing standard corrected count increment or percent PLT recovery (PPR) calculations, male patients showed inferior recovery rates, irrespective of donor sex. Using an adjusted PPR, which takes into account differences in blood volume between males and females, neither donor nor recipient sex played any role in PLT recovery after transfusion. Similarly, the time to next PLT transfusion was unaffected by both donor and recipient sex. In a subgroup analysis of patients with graft‐versus‐host disease after allogeneic HSCT, male recipients of a female allograft—which may carry anti‐H‐Y T cells and antibodies—had significantly lower time to next PLT transfusion. However, this occurred after both male donor and female donor PLT transfusions, arguing against an involvement of alloreactivity against H‐Y antigens on PLTs.ConclusionThis large analysis found no evidence that donor‐recipient sex matching influences the outcome of PLT transfusion.
Use of human embryonic stem cells and umbilical cord blood stem cells for research and therapy: a prospective survey among health care professionals and patients in Switzerland
Authors: Wagner Anna Margaretha , Krenger Werner , Holzgreve Wolfgang , Bürkli Peter , Surbek Daniel V. 
Published: March 2013

BackgroundScientific progress in the biology of hematopoietic stem cells (HSCs) provides opportunities for advances in therapy for different diseases. While stem cell sources such as umbilical cord blood (UCB) are unproblematic, other sources such as human embryonic stem cells (hESCs) raise ethical concerns.Study Design and MethodsIn a prospective survey we established the ethical acceptability of collection, research, and therapy with UCB HSCs versus hESCs among health care professionals, pregnant women, patients undergoing in vitro fertilization therapy, parents, and HSC donors and recipients in Switzerland.ResultsThere was overall agreement about an ethical justification for the collection of UCB for research and therapy in the majority of participants (82%). In contrast, research and therapy with hESCs was acceptable only by a minority (38% of all responders). The collection of hESCs solely created for HSC collection purposes met overall with the lowest approval rates. Hematologists displayed among the participants the highest acceptance rates for the use of hESCs with 55% for collection, 63% for research, and 73% for therapy.ConclusionsThis is the first study assessing the perception of hESCs for research and therapy in comparison with UCB HSCs in different target groups that are exposed directly, indirectly, or not at all to stem cell–based medicine. Our study shows that the debate over the legitimacy of embryo‐destructive transplantation medicine is far from over as particularly hESC research continues to present an ethical problem to an overwhelming majority among laypersons and even among health care professionals.
Prolonged ceftriaxone‐induced immune thrombocytopenia due to impaired drug clearance: a case report
Authors: Jacquot Cyril , Moayeri Morvarid , Kim Benjamin , Shugarts Sarah , Lynch Kara L. , Leavitt Andrew D. 
Published: March 2013

BackgroundAntibody‐mediated drug‐induced thrombocytopenia (DIT) typically requires the presence of the sensitizing drug in the plasma. Therefore, platelet (PLT) counts often start to recover 1 to 2 days after discontinuation of the offending medication. We present a case of ceftriaxone‐induced DIT that resulted in severe, prolonged thrombocytopenia.Case ReportA 65‐year‐old woman with liver and renal insufficiency was transferred to our hospital for liver transplant evaluation. Two days after a 5‐day course of ceftriaxone, her PLT count declined from a stable baseline of approximately 70 × 109/L to a value of 3 × 109/L, with coincident onset of mucocutaneous purpura. Her PLT count remained in the 1 × 109 to 6 × 109/L range until her death 13 days later, despite intravenous immune globulin, steroids, and PLT transfusions. The persistently low PLT count impeded central catheter placement for hemodialysis and possible therapeutic plasmapheresis. A strong ceftriaxone‐dependent, PLT‐reactive antibody was identified in a sample drawn 7 days after ceftriaxone was last administered, and ceftriaxone remained detectable in her serum for at least 8 days after the last dose.ConclusionA ceftriaxone‐dependent, PLT‐reactive antibody was responsible for the persistent thrombocytopenia in this patient. Although DIT is generally expected to improve within a few days of drug discontinuation, impaired drug clearance can significantly alter the outcome. This case highlights the importance of altered drug metabolism and clearance in critically ill patients, especially those with combined hepatic and renal dysfunction. DIT should be strongly suspected in patients with acute thrombocytopenia, and all treatment options to reduce serum drug levels should be seriously considered.
Antagonist Antibodies to PD-1 and B7-H1 (PD-L1) in the Treatment of Advanced Human Cancer
Authors: Sznol Mario , Chen Lieping 
Published: March 2013

AbstractThe immune suppressive molecule programmed death-1 (PD-1) is upregulated in activated T lymphocytes and inhibits T-cell function upon binding to its ligands B7-H1 (PD-L1, CD274) and B7-DC (PD-L2, CD273). Substantial experimental data from in vitro cell culture systems and animal models, and more recently from clinical trials, indicate that PD-1/PD-1-ligand interactions are a major mechanism of immune suppression within the tumor microenvironment. Initial clinical studies of antibodies directed against PD-1 and B7-H1 showed both an encouraging safety profile and remarkable antitumor activity in subsets of patients with metastatic disease, including malignancies—such as lung cancer—which were previously thought to be unresponsive to immunotherapy. Preliminary data have suggested a correlation between tumor membrane B7-H1 expression and clinical response to anti-PD-1 antibodies. Several key challenges remain to optimize development of PD-1/B7-H1 pathway blockade, including defining the biologic significance of all potential ligand–receptor interactions in the tumor microenvironment, developing more accurate predictive biomarkers of response, determining the breadth of activity in human malignancies, and developing rational combinations of therapy that address key mechanisms involved in positive and negative regulation of antitumor immune responses. Clin Cancer Res; 19(5); 1021–34. ©2013 AACR.
Agonistic CD40 Antibodies and Cancer Therapy
Authors: Vonderheide Robert H. , Glennie Martin J. 
Published: March 2013

Abstract
Recent success in cancer immunotherapy has reinvigorated the hypothesis that the immune system can control many if not most cancers, in some cases producing durable responses in a way not seen with many small-molecule drugs. Agonistic CD40 monoclonal antibodies (mAb) offer a new therapeutic option which has the potential to generate anticancer immunity by various mechanisms. CD40 is a TNF receptor superfamily member expressed broadly on antigen-presenting cells (APC) such as dendritic cells, B cells, and monocytes as well as many nonimmune cells and a range of tumors. Agonistic CD40 mAb have been shown to activate APC and promote antitumor T-cell responses and to foster cytotoxic myeloid cells with the potential to control cancer in the absence of T-cell immunity. Thus, agonistic CD40 mAb are fundamentally different from mAb which block negative immune checkpoint such as anti-CTLA-4 or anti-PD-1. Initial clinical trials of agonistic CD40 mAb have shown highly promising results in the absence of disabling toxicity, both in single-agent studies and in combination with chemotherapy; however, numerous questions remain about dose, schedule, route of administration, and formulation. Recent findings about the role played by the IgG isotype and the Fc gamma receptor (FcγR) in mAb cross-linking, together with insights into mechanisms of action, particularly with regard to the role of myeloid cells, are predicted to help design next-generation CD40 agonistic reagents with greater efficacy. Here, we will review the preclinical and clinical data and discuss the major issues facing the field. Clin Cancer Res; 19(5); 1035–43. ©2013 AACR.
Use of Oligonucleotide Aptamer Ligands to Modulate the Function of Immune Receptors
Authors: Gilboa Eli , McNamara James , Pastor Fernando 
Published: March 2013

Abstract
The paucity of costimulation at the tumor site compromises the ability of tumor-specific T cells to eliminate the tumor. The recent U.S. Food and Drug Administration approval of ipilumimab, an antibody that blocks the inhibitory action of CTLA-4, and clinical trials targeting 4-1BB and PD-1 or PD-L1, have underscored the therapeutic potential of using immunomodulatory antibodies to stimulate protective immunity in human patients. Nonetheless, systemic administration of immunomodulatory antibodies has been associated with dose-limiting autoimmune pathologies, conceivably reflecting also the activation of resident autoreactive T cells. Arguably, targeting immunomodulatory ligands to the disseminated tumor lesions of the patient would reduce such drug-associated toxicities. We have recently developed a new class of inhibitory (CTLA-4) and agonistic (4-1BB and OX-40) ligands composed of short oligonucleotide (ODN) aptamers that exhibited bioactivities comparable or superior to that of antibodies. To reduce toxicity, the immunomodulatory aptamers were targeted to the tumor by conjugation to a second aptamer that bound to a product expressed on the surface of the tumor cell, the targeting aptamer, generating a bispecific aptamer conjugate analogous to bispecific antibodies. In a proof-of-concept study in mice, we have shown that an agonistic 4-1BB–binding aptamer conjugated to a prostate-specific membrane antigen (PSMA)–binding aptamer led to the inhibition of PSMA-expressing tumors, was more effective than, and synergized with, vaccination, and exhibited a superior therapeutic index compared with nontargeted costimulation with 4-1BB antibodies or 4-1BB aptamers. The cell-free chemically synthesized ODN aptamers offer significant advantages over antibodies in terms of synthesis, cost, as well as conjugation chemistry needed to generate bispecific ligand fusions. Clin Cancer Res; 19(5); 1054–62. ©2012 AACR.
Morphological and molecular characterisation of Californian species of Metaporcelaimus Lordello, 1965 (Dorylaimida, Aporcelaimidae), with a new concept of the genus
Authors: Álvarez-Ortega Sergio , Subbotin Sergei A. , Peña-Santiago Reyes 
Published: March 2013

Two new and one known species of Metaporcelaimus from Californian natural habitats were studied using morphological and molecular approaches. Metaporcelaimus marinensis sp. n. is characterised by its body 1.99-2.48 mm long, lip region offset by deep constriction and 14-15 μm broad, odontostyle 13-15 μm long, neck 456-529 μm long, pharyngeal expansion occupying 47-50% of total neck length, pharyngo-intestinal junction bearing a dorsal lobe, uterus tripartite and 201-262 μm long, pars refringens vaginae well developed, V = 55-58, tail conical (43-55 μm, c = 43-52, c′ = 1.3-1.6) with its inner core somewhat notched and nearly reaching the tip, spicules 54-63 μm long and 6-7 spaced ventromedian supplements located outside the range of the spicules. Metaporcelaimus ovogranulosus sp. n. is distinguished in having body 1.54-1.96 mm long, lip region offset by deep constriction and 17-19 μm broad, odontostyle 17-19 μm long, neck 415-539 μm long, pharyngeal occupying 49-53% of total neck length, uterus simple and 27-41 μm long, uterine eggs granulate, pars refringens vaginae well developed, V = 48-51, tail conical (35-44 μm, c = 39-52, c′ = 1.4-1.6) with its inner core notched and nearly reaching the tip, and male unknown. Measurements and LM illustrations are also provided for M. capitatus. Metaporcelaimus was morphologically compared with Aporcelaimellus. The analysis revealed that these genera are barely distinguishable from each other. Aporcelaimellus species can be separated into two groups, one of them being morphologically similar to Metaporcelaimus. Molecular data and the derived evolutionary tree show that Metaporcelaimus and Aporcelaimellus do not share a recent common ancestor. Consequently, a new concept is proposed for Metaporcelaimus, M. ahmadi sp. n. is proposed for A. coomansi apud Ahmad nec Baqri & Khera, and 16 species of Aporcelaimellus are transferred to Metaporcelaimus. An updated list of Metaporcelaimus species with their synonyms, a key to their identification and a tabular compendium with important taxonomic morphometric characters are given.
Description of Aphelenchoides xui sp. n. (Nematoda: Aphelenchoididae) in packaging wood from South Africa
Authors: Wang Xuan , Wang Pei , Gu Jianfeng , Wang Jiangling , Li Hongmei 
Published: March 2013

Aphelenchoides xui sp. n. is described and illustrated from imported packaging wood from South Africa intercepted at Ningbo Port, China. The new species has a body length of 564-820 μm (males) and 549-882 μm (females). The cuticle is weakly annulated with four lines in the lateral field. The stylet is 11-13 μm long and has small basal swellings. The excretory pore is located ca one body diam. posterior to the median bulb, or 75-100 μm from the head. Spicules are relatively large (18-23 μm) with apex and rostrum rounded and well developed and the end of the dorsal limb clearly curved ventrad like a hook. The male tail bears six (2 + 2 + 2) caudal papillae. The spermatheca is axial and oblong and contains disc-like sperm. The female tail is conical, terminating in a complicated step-like projection, usually with many tiny nodular protuberances. The new species is morphologically similar to A. arcticus, A. haguei and A. parasaprophilus in Group 2 sensu Shahina, but is distinguished by spicule shape and form of the female tail terminus. Phylogenetic analysis based on SSU and partial LSU sequences revealed that A. xui sp. n. was closest to A. varicaudatus, although some species of Laimaphelenchus and Schistonchus were also included in the same branch.