bluuebunny/crossref_metadata_2025 huggingface dataset:
Directed Differentiation of Oligodendrocyte Progenitor Cells from Mouse Induced Pluripotent Stem Cells
Authors: Terzic Dino , Maxon Jacob R. , Krevitt Leah , Dibartolomeo Christina , Goyal Tarini , Low Walter C. , Dutton James R. , Parr Ann M.
Published: February 2016

Several neurological disorders, such as multiple sclerosis, the leukodystrophies, and traumatic injury, result in loss of myelin in the central nervous system (CNS). These disorders may benefit from cell-based therapies that prevent further demyelination or are able to restore lost myelin. One potential therapeutic strategy for these disorders is the manufacture of oligodendrocyte progenitor cells (OPCs) by the directed differentiation of pluripotent stem cells, including induced pluripotent stem cells (iPSCs). It has been proposed that OPCs could be transplanted into demyelinated or dysmyelinated regions of the CNS, where they would migrate to the area of injury before terminally differentiating into myelinating oligodendrocytes. OPCs derived from mouse iPSCs are particularly useful for modeling this therapeutic approach and for studying the biology of oligodendrocyte progenitors because of the availability of mouse models of neurological disorders associated with myelin deficiency. Moreover, the utility of miPSC-derived OPCs would be significantly enhanced by the adoption of a consistent, reproducible differentiation protocol that allows OPCs derived from different cell lines to be robustly characterized and compared. Here we describe a standardized, defined protocol that reliably directs the differentiation of miPSCs to generate high yields of OPCs that are capable of maturing into oligodendrocytes.
Transplanted Peripheral Blood Stem Cells Mobilized by Granulocyte Colony-Stimulating Factor Promoted Hindlimb Functional Recovery after Spinal Cord Injury in Mice
Authors: Takahashi Hiroshi , Koda Masao , Hashimoto Masayuki , Furuya Takeo , Sakuma Tsuyoshi , Kato Kei , Okawa Akihiko , Inada Taigo , Kamiya Koshiro , Ota Mitsutoshi , Maki Satoshi , Takahashi Kazuhisa , Yamazaki Masashi , Mannoji Chikato
Published: February 2016

Granulocyte colony-stimulating factor (G-CSF) mobilizes peripheral blood stem cells (PBSCs) derived from bone marrow. We hypothesized that intraspinal transplantation of PBSCs mobilized by G-CSF could promote functional recovery after spinal cord injury. Spinal cords of adult nonobese diabetes/severe immunodeficiency mice were injured using an Infinite Horizon impactor (60 kdyn). One week after the injury, 3.0 μl of G-CSF-mobilized human mononuclear cells (MNCs; 0.5 × 105/μl), G-CSF-mobilized human CD34-positive PBSCs (CD34; 0.5 × 105/μl), or normal saline was injected to the lesion epicenter. We performed immunohistochemistry. Locomotor recovery was assessed by Basso Mouse Scale. The number of transplanted human cells decreased according to the time course. The CD31-positive area was significantly larger in the MNC and CD34 groups compared with the vehicle group. The number of serotonin-positive fibers was significantly larger in the MNC and CD34 groups than in the vehicle group. Immunohistochemistry revealed that the number of apoptotic oligodendrocytes was significantly smaller in cell-transplanted groups, and the areas of demyelination in the MNC- and CD34-transplanted mice were smaller than that in the vehicle group, indicating that cell transplantation suppressed oligodendrocyte apoptosis and demyelination. Both the MNC and CD34 groups showed significantly better hindlimb functional recovery compared with the vehicle group. There was no significant difference between the two types of transplanted cells. Intraspinal transplantation of G-CSF-mobilized MNCs or CD34-positive cells promoted angiogenesis, serotonergic fiber regeneration/sparing, and preservation of myelin, resulting in improved hindlimb function after spinal cord injury in comparison with vehicle-treated control mice. Transplantation of G-CSF-mobilized PBSCs has advantages for treatment of spinal cord injury in the ethical and immunological viewpoints, although further exploration is needed to move forward to clinical application.
Characterization of HLA-G and Related Immunosuppressive Effects in Human Umbilical Cord Stroma-Derived Stem Cells
Authors: Ding Dah-Ching , Chou Hsiang-Lan , Chang Yu-Hsun , Hung Wei-Ting , Liu Hwan-Wun , Chu Tang-Yuan
Published: February 2016

Mesenchymal stem cells (MSCs) and especially those derived from fetal tissues exert a potent immunosuppressive effect that can be enhanced under inflammatory conditions. This study aimed to explore the immunosuppressive properties of human umbilical cord mesenchymal stem cells (HUCMSCs). We found that HLA-G, the nonclassical HLA allele with strong immune-inhibitory properties, was much more expressed on the HUCMSCs than on MSCs of other origins. Flow cytometry revealed that 90.8% of the HUCMSCs expressed HLA-G. RT-PCR revealed expression of HLA-G1, HLA-G5, and HLA-G7 in all of four HUCMSC lines. In a mixed lymphocyte reaction assay, the HUCMSCs inhibited the proliferation of lymphocytes by 35 ± 3% and could be reversed by treatment with an HLA-G blocking antibody. Upon coculture with the HUCMSCs, peripheral blood mononuclear cells expressed lower levels of proinflammatory mediators such as IL-6, TNF-α, and VEGF-α. This immunosuppressive effect was enhanced when the HUCMSCs were pretreated with IFN-γ, such that the expression of HLA-G was highly activated and HLA-DR diminished. The same phenomenon was not observed in MSCs derived from bone marrow or the placenta. In a xenograft rejection assay, the HUCMSCs survived in immunocompetent mice, whereas primary fibroblasts did not survive. This study confirms the HLA-G-related immunosuppressive property of HUCMSCs, which is more potent than MSCs of other origin. A good tolerance of this mesenchymal stem cell in allogeneic transplantation can thus be anticipated.
Intra-arterial Administration of Placenta-Derived Decidual Stromal Cells to the Superior Mesenteric Artery in the Rabbit: Distribution of Cells, Feasibility, and Safety
Authors: Arnberg Fabian , Lundberg Johan , Olsson Annie , Samén Erik , Jaff Nasren , Jussing Emma , Dahlén Ulrika , Nava Silvia , Axelsson Rimma , Ringdén Olle , Kaipe Helen , Holmin Staffan
Published: February 2016

Selective administration of mesenchymal stromal cells to the mesenteric arteries is a potential technique to overcome pulmonary trapping and increase the density of transplanted cells in extensive mural inflammation of the intestine, such as in inflammatory bowel disease and graft-versus-host disease. We injected 5 × 106 111In-oxine-labeled human decidual stromal cells (DSCs) to the rabbit superior mesenteric artery (SMA) using clinical routine catheters guided by an angiographical system under sterile conditions. We used longitudinal single-photon emission tomography at 6 h and at 1, 2, and 5 days to assess trafficking and distribution of DSCs. We used digital subtraction angiography, computed tomography, and hematoxylin and eosin stainings to determine biodistribution of cells and to assess safety end points. We found that selective injection of human DSCs to the rabbit SMA does not result in acute embolic complications. Furthermore, we found that IV administration resulted in extensive retention of the radiolabeled DSCs in the lungs, corroborating previous studies on pulmonary trapping. In sharp contrast, selective injections to the SMA resulted in uptake distributed in the intestine supplied by the SMA and in the liver, indicating that this approach could significantly increase the fraction of injected DSCs reaching the target tissue.
Numb Expression Contributes to the Maintenance of an Undifferentiated State in Human Epidermis
Authors: Iannolo Gioacchin , Sciuto Maria Rita , Buccheri Simona , Colarossi Cristina , De Maria Ruggero , Memeo Lorenzo , Conaldi Pier Giulio
Published: February 2016

The epidermis is a stratified epithelium with a stem cell subpopulation in the basal layer that constantly replicates and periodically detaches from the base, undergoing a differentiation process that involves various developmental signals and regulatory pathways. During the last 10 years, a number of studies tried to elucidate the intricate scenario that maintains the epithelial shield during the entire life span. In our study, we investigated the role of Numb in the skin compartment and, in particular, its involvement in stem cell maintenance. Numb expression in the skin compartment was assessed by immunofluorescence and immunohistochemistry analysis. We evaluated Numb expression in primary epithelial cells at various differentiative stages. Moreover, we overexpressed Numb in the isolated population enriched for undifferentiated progenitors to establish its involvement in in vitro differentiation. We demonstrated that Numb in high-proliferating epithelial undifferentiated progenitors contributes to the maintenance of an undifferentiated state. This regulation involves the E3 ligases Itch binding. Moreover, the analysis of a cohort of cutaneous carcinomas showed that Numb is highly expressed in squamous cell carcinoma (SCC), where we observed a direct correlation between the expression of Numb and Ki-67. Our data indicate for the first time that Numb is involved in the maintenance of the undifferentiated proliferating stem cell pool in the epithelial basal layer and its expression could become a new marker in skin cancer.
Retinal Angiogenesis Effects of TGF-β1 and Paracrine Factors Secreted from Human Placental Stem Cells in Response to a Pathological Environment
Authors: Kim Kyung-Sul , Park Ji-Min , Kong Taeho , Kim Chul , Bae Sang-Hun , Kim Han Wool , Moon Jisook
Published: February 2016

Abnormal angiogenesis is a primary cause of many eye diseases, including diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity. Mesenchymal stem cells (MSCs) are currently being investigated as a treatment for several such retinal diseases based on their neuroprotective and angiogenic potentials. In this study, we evaluated the role of systemically injected human placental amniotic membrane-derived MSCs (AMSCs) on pathological neovascularization of proliferative retinopathy. We determined that AMSCs secrete higher levels of transforming growth factor-β (TGF-β1) than other MSCs, and the secreted TGF-β1 directly suppresses the proliferation of endothelial cells under pathological conditions in vitro. Moreover, in a mouse model of oxygen-induced retinopathy, intraperitoneally injected AMSCs migrated into the retina and suppressed excessive neovascularization of the vasculature via expression of TGF-β1, and the antineovascular effect of AMSCs was blocked by treatment with TGF-β1 siRNA. These findings are the first to demonstrate that TGF-β1 secreted from AMSCs is one of the key factors to suppress retinal neovascularization in proliferative retinopathy and further elucidate the therapeutic function of AMSCs for the treatment of retinal neovascular diseases.
Effects of Transplantation of CTLA4Ig-Overexpressing Adipose Tissue-Derived Mesenchymal Stem Cells in Mice with Sustained Severe Rheumatoid Arthritis
Authors: Choi Eun Wha , Shin Il Seob , Song Ji Woo , Lee Minjae , Yun Tae Won , Yang Jehoon , Choi Kyu-Sil , Kim Sung-Joo
Published: February 2016

CTLA4Ig has therapeutic potential for rheumatoid arthritis patients unresponsive to methotrexate (MTX) or TNF-α blockers. However, recombinant CTLA4Ig proteins are short acting and expensive. Adipose tissue-derived mesenchymal stem cells (ASCs) present an ideal stem cell source for practical regenerative medicine due to their abundant availability and their beneficial properties including immunomodulation, homing activity, paracrine effects, and differentiation ability. Therefore, we aimed to determine whether CTLA4Ig and human ASCs show synergistic effects on immunomodulation and clinical improvement of sustained severe rheumatoid arthritis in a mouse model. hASCs overexpressing CTLA4Ig (CTLA4Ig–hASC) were serially transplanted into mice with collagen-induced arthritis. Arthritic mice were subjected to four treatments based on their arthritis score on day 62 postimmunization: control (C group), hASC (H group), CTLA4Ig–hASC (CT group), and MTX (MTX group). A group of healthy mice was used as a normal control (N). Mice in the N and C groups were infused with 150 μl saline, and 2 × 106hASCs or CTLA4Ig–hASCs in 150 μl of saline were intravenously administered to those in the H and CT groups, respectively, on days 63, 70, 77, and 84 after CII immunization. About 1 mg/kg of methotrexate was intraperitoneally administered to the MTX group three times a week for 4 weeks. Serial hASC and CTLA4Ig–hASC transplantation modulated various cytokines and chemokines related to the development of rheumatoid arthritis. Both treatments protected against destruction of cartilage, with CTLA4Ig–hASCs being most effective. Serum levels of CII autoantibodies and C-telopeptide of type II collagen were significantly low in the group transplanted with CTLA4Ig–hASCs. In vitro, ASC and CTLA4Ig–hASC treatment significantly decreased T-bet and GATA-3 expression in splenocytes from arthritic mice, and CTLA4Ig–hASC treatment significantly increased the ratio of Treg/Th17 (CD4+CD25+FoxP3+/CD4+CD25+RORγt) cells. Serial hASC and CTLA4Ig–hASC transplantation offers promising treatment for rheumatoid arthritis, and CTLA4Ig–hASCs showed stronger therapeutic effects than nontransduced hASCs.
Evidence of a Pivotal Role for the Distal Part of the Complement Cascade in the Diurnal Release of Hematopoietic Stem Cells into Peripheral Blood
Authors: Borkowska Sylwia , Suszynska Malwina , Ratajczak Janina , Ratajczak Mariusz Z.
Published: February 2016

We found that diurnal activation of the three evolutionarily ancient proteolytic cascades in peripheral blood (PB), namely, the complement, coagulation, and fibrinolytic cascades, late at night or in the early morning hours, precedes the diurnal release of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM) into PB in wild-type mice. Moreover, activation of the distal part of the complement cascade (ComC), involving cleavage of the fifth component (C5), seems to play a crucial role in pharmacological mobilization of HSPCs. In order to shed more light on the role of diurnal rhythms in the egress of HSPCs, we studied diurnal changes in the number of circulating HSPCs in C5-deficient mice and did not observe diurnal changes in the number of these cells circulating in PB in C5-/- animals. Based on this finding, we conclude that activation of the distal part of the ComC, C5 cleavage, and release of C5a and desArgC5a are required in executing the diurnal release of HSPCs from BM into PB. Moreover, the fact that C5-/- mice still displayed normal activation of the coagulation and fibrinolytic cascades indicates that, of all the proteolytic cascades, the ComC is the dominant player regulating diurnal egress of HSPCs.
Induced Pluripotent Stem Cell-Derived Conditioned Medium Attenuates Acute Kidney Injury by Downregulating the Oxidative Stress-Related Pathway in Ischemia–Reperfusion Rats
Authors: Tarng Der-Cherng , Tseng Wei-Cheng , Lee Pei-Ying , Chiou Shih-Hwa , Hsieh Shie-Liang
Published: February 2016

Teratoma-like formation addresses a critical safety concern for the potential utility of induced pluripotent stem cells (iPSCs). Therefore, therapy utilizing iPSC-derived conditioned medium (iPSC-CM) for acute kidney injury (AKI) has attracted substantial interest. A recent study showed that iPSC-CM effectively alleviated ventilator-induced lung injury in rats. It prompts us to assess the therapeutic effects of iPSC-CM on ischemic AKI. First, we assessed the changes in renal function and tubular cell apoptosis by intraperitoneal administration of iPSC-CM to ischemia–reperfusion (I/R) rats. Second, we explored the oxidative stress-related pathway in the apoptosis of renal tubular cells subjected to hypoxia–reoxygenation (H/R). Administration of iPSC-CM significantly improved renal function and protected tubular cells against apoptosis in rats with I/R-AKI, and the optimal effect was observed at the 50-fold concentrated iPSC-CM. iPSC-CM also mitigated the H/R-induced apoptosis of NRK-52E cells in vitro. Reactive oxygen species (ROS) production was augmented in kidneys following I/R and in NRK-52E cells subjected to H/R. Meanwhile, expressions of phosphorylated p38 MAPK, TNF-α, and cleaved caspase 3 and NF-κB activity were consistently increased in vivo and in vitro. Following administration of iPSC-CM, ROS production was abolished, and inflammatory cytokine expression was significantly suppressed. Annexin V–propidium iodide flow cytometry and in situ TUNEL assay further showed that iPSC-CM markedly attenuated H/R- or I/R-induced tubular cell apoptosis. Intriguingly, treatment with iPSC-CM significantly improved the survival of rats with I/R-induced AKI. iPSC-CM represents a favorable source of stem cell-based therapy and may serve as a potential therapeutic strategy for kidney repair in ischemic AKI.
Functional Repair of Rat Corticospinal Tract Lesions Does Not Require Permanent Survival of an Immunoincompatible Transplant
Authors: Li Ying , Li Daqing , Raisman Geoffrey
Published: February 2016

Cell transplantation is one of the most promising strategies for repair of human spinal cord injuries. Animal studies from a number of laboratories have shown that transplantation of olfactory ensheathing cells cultured from biopsies of the olfactory bulb mediate axonal regeneration and remyelination and restore lost functions in spinal cord injuries. For translation from small laboratory experimental injuries to the large spinal cord injuries encountered in human patients the numbers of cells that can be obtained from a patient's own olfactory bulb becomes a serious limiting factor. Furthermore, removal of an olfactory bulb requires invasive surgery and risks unilateral anosmia. We here report that xenografted mouse bulbar olfactory ensheathing cells immunoprotected by daily cyclosporine restore directed forepaw reaching function in rats with chronic C1/2 unilateral corticospinal tract lesions. Once function had been established for 10 days, cyclosporine was withdrawn. Thirteen out of 13 rats continued to increase directed forepaw reaching. Immunohistochemistry shows that in all cases neurofilament-positive axons were present in the lesion, but that the grafted cells had been totally rejected. This implies that once grafted cells have acted as bridges for axon regeneration across the lesion site their continued presence is no longer necessary for maintaining the restored function. This raises the possibility that in the future a protocol of temporary immunoprotection might allow for the use of the larger available numbers of immunoincompatible allografted cells or cell lines, which would avoid the need for removing a patient's olfactory bulb.
Hematopoietic Cell and Renal Transplantation in Plasma Cell Dyscrasia Patients
Authors: Baraldi Olga , Grandinetti Valeria , Donati Gabriele , Comai Giorgia , Battaglino Giuseppe , Cuna Vania , Capelli Irene , Sala Elisa , La Manna Gaetano
Published: February 2016

Gammopathies, multiple myeloma, and amyloidosis are plasma dyscrasias characterized by clonal proliferation and immunoglobulin overproduction. Renal impairment is the most common and serious complication with an incidence of 20–30% patients at the diagnosis. Kidney transplant has not been considered feasible in the presence of plasma dyscrasias because the immunosuppressive therapy may increase the risk of neoplasia progression, and paraproteins may affect the graft. However, recent advances in clinical management of multiple myeloma and other gammopathies allow considering kidney transplant as a possible alternative to dialysis. Numerous evidence indicates the direct relationship between hematological remission and renal function restoring. The combination of kidney and hematopoietic cell transplant has been reported as a promising approach to reestablish end-organ function and effectively treat the underlying disease. This review describes current protocols used to perform kidney transplantation in patients with plasma dyscrasias.
Fetal Cartilage-Derived Cells Have Stem Cell Properties and Are a Highly Potent Cell Source for Cartilage Regeneration
Authors: Choi Woo Hee , Kim Hwal Ran , Lee Su Jeong , Jeong Nayoung , Park So Ra , Choi Byung Hyune , Min Byoung-Hyun
Published: February 2016

Current strategies for cartilage cell therapy are mostly based on the use of autologous chondrocytes or mesenchymal stem cells (MSCs). However, these cells have limitations of a small number of cells available and of low chondrogenic ability, respectively. Many studies now suggest that fetal stem cells are more plastic than adult stem cells and can therefore more efficiently differentiate into target tissues. However, the characteristics and the potential of progenitor cells from fetal tissue remain poorly defined. In this study, we examined cells from human fetal cartilage at 12 weeks after gestation in comparison with bone marrow-derived MSCs or cartilage chondrocytes from young donors (8–25 years old). The fetal cartilage-derived progenitor cells (FCPCs) showed higher yields by approximately 24 times than that of chondrocytes from young cartilage. The morphology of the FCPCs was polygonal at passage 0, being similar to that of the young chondrocytes, but it changed later at passage 5, assuming a fibroblastic shape more akin to that of MSCs. As the passages advanced, the FCPCs showed a much greater proliferation ability than the young chondrocytes and MSCs, with the doubling times ranging from 2~4 days until passage 15. The surface marker profile of the FCPCs at passage 2 was quite similar to that of the MSCs, showing high expressions of CD29, CD90, CD105, and Stro-1. When compared to the young chondrocytes, the FCPCs showed much less staining of SA-β-gal, a senescence indicator, at passage 10 and no decrease in SOX9 expression until passage 5. They also showed a much greater chondrogenic potential than the young chondrocytes and the MSCs in a three-dimensional pellet culture in vitro and in polyglycolic acid (PGA) scaffolds in vivo. In addition, they could differentiate into adipogenic and osteogenic lineages as efficiently as MSCs in vitro. These results suggest that FCPCs have stem cell properties to some extent and that they are more active in terms of proliferation and chondrogenic differentiation than young chondrocytes or MSCs.
Pediatric Audiology in North America: Current Clinical Practice and How It Relates to the American Academy of Audiology Pediatric Amplification Guideline
Authors: Moodie Sheila , Rall Eileen , Eiten Leisha , Lindley George , Gordey Dave , Davidson Lisa , Bagatto Marlene , Scollie Susan
Published: February 2016

Background:There is broad consensus that screening and diagnosis of permanent hearing loss in children must be embedded within a comprehensive, evidence-based, family-centered intervention program. Clinical practice guidelines (CPGs) for pediatric hearing assessment and hearing
aid verification aim to reduce variability in practice and increase the use of effective evidence-based diagnostic and treatment options so that optimal outcomes may be achieved. To be of value, guidelines must be translated and implemented into practice and ongoing monitoring of their use
in practice should occur.Purpose:This paper provides the results of two studies that aim to examine current pediatric audiology and amplification practice in North America.Research Design:A concurrent embedded mixed methods design was used.Study Sample:An electronic survey
was distributed to North American audiologists who delivered pediatric audiology services with 350 audiologists participating in study 1 and 63 audiologists participating in study 2.Data Collection and Analysis:A quantitative approach was the predominant method of data collection. Respondents
were prompted to provide additional qualitative text and detail regarding their quantitative response choice. This qualitative text was used during the analysis phase and combined with quantitative results to assist understanding of respondents’ knowledge, skills, and barriers/facilitators
to implement best practice in pediatric amplification.Results:Approximately 70% of audiologists reported using best-practice protocols for pediatric hearing aid fitting. Despite widespread knowledge and increased use of CPGs over the last 18 yrs, results of these studies show that variation
in practice patterns continue to exist. Several examples of implementation challenges are discussed with recommendations provided.Conclusions:In order for audiologists working with children who are deaf or hard of hearing and their families to achieve the principles of family-centered
early intervention, practice guidelines must continue to be developed, disseminated, and translated as they have a positive impact on the services provided. Researchers and clinical audiologists who deliver services must continue to collaborate to understand the “how” and “why”
of implementing guidelines into practice and to identify the barriers/facilitators encountered in trying to do so.
Hearing Aid Patient Education Materials: Is There Room for Improvement?
Authors: Joseph John , Svider Peter F. , Shaigany Kevin , Eloy Jean Anderson , McDonald Paulette G. , Folbe Adam J. , Hong Robert S.
Published: February 2016

Purpose:The purpose of this study was to analyze and compare the readability of patient education materials (PEMs) from leading manufacturers of behind-the-ear style hearing aids and popular hearing aid information Web sites to determine if they meet guidelines recommended by
public health agencies.Research Design:Analysis of hearing aid PEMs.Methods:Printed user guides from six of the leading manufacturers of BTE hearing aids and 15 of the most popular hearing aid‐information Web sites were accessed online and analyzed for readability using
the Gunning-Fog Index, New Fog Count, Raygor Estimate Graph, Simple Measure of Gobbledygook, and Flesch Reading Ease score.Results:Overall average grade‐level readability for all six printed manufacturer user manuals was calculated to be written at a 10th grade reading level.
Overall average grade-level readabilities for all 15 popular online hearing aid‐information Web sites representing professional organizations, suppliers, and health information services were calculated to be written at 10th, 10th, and 11th grade reading levels, respectively. Average
Flesch Reading Ease scores for all printed guides and online patient information Web sites were calculated to fall within the fairly difficult category for readability.Conclusions:PEMs provided by top hearing aid manufactures and popular hearing aid Web sites are written well above
the reading level recommended by the National Institutes of Health. Consideration should be given toward simplifying these materials in order to enhance user experience and increase compliance among behind-the-ear hearing aid users.
MEASUREMENT OF THE RADIATIVE DECAY RATE AND ENERGY OF THE METASTABLE
LEVEL IN Fe xvii
Authors: Beiersdorfer P. , López-Urrutia J. R. Crespo , Träbert E.
Published: February 2016

Measurements at the Livermore electron beam ion trap have been performed in order to infer the energy and the radiative lifetime of the

level in the Fe xvii spectrum. This is the longest-lived level in the neonlike iron ion, and its radiative decay produces the Fe xvii line at 1153 Å, feeding the population of the

upper level of one of the most prominent lines in the Fe xvii L-shell X-ray spectrum, commonly dubbed

. In the presence of a strong (

few kG) magnetic field, the

level has a finite probability to decay directly to the

neonlike ground level via the emission of an L-shell X-ray. Our measurements allow us to observe this X-ray line in the Fe xvii L-shell spectrum and from it to infer the radiative rate for the magnetic dipole decay of the

level to the

. Our result of

s−1 is in agreement with predictions. We have also measured the wavelength of the associated X-ray line to be 16.804 ± 0.002 Å, which means that the line is displaced 1.20 ± 0.05 eV from the neighboring

transition, commonly labeled

. From our measurement, we infer 5950570 ± 710 cm−1 for the energy of the

level.
THE SPECTRAL AMPLITUDE OF STELLAR CONVECTION AND ITS SCALING IN THE HIGH-RAYLEIGH-NUMBER REGIME
Authors: Featherstone Nicholas A. , Hindman Bradley W.
Published: February 2016

Convection plays a central role in the dynamics of any stellar interior, and yet its operation remains largely hidden from direct observation. As a result, much of our understanding concerning stellar convection necessarily derives from theoretical and computational models. The Sun is, however, exceptional in that regard. The wealth of observational data afforded by its proximity provides a unique test bed for comparing convection models against observations. When such comparisons are carried out, surprising inconsistencies between those models and observations become apparent. Both photospheric and helioseismic measurements suggest that convection simulations may overestimate convective flow speeds on large spatial scales. Moreover, many solar convection simulations have difficulty reproducing the observed solar differential rotation owing to this apparent overestimation. We present a series of three-dimensional stellar convection simulations designed to examine how the amplitude and spectral distribution of convective flows are established within a star’s interior. While these simulations are nonmagnetic and nonrotating in nature, they demonstrate two robust phenomena. When run with sufficiently high Rayleigh number, the integrated kinetic energy of the convection becomes effectively independent of thermal diffusion, but the spectral distribution of that kinetic energy remains sensitive to both of these quantities. A simulation that has converged to a diffusion-independent value of kinetic energy will divide that energy between spatial scales such that low-wavenumber power is overestimated and high-wavenumber power is underestimated relative to a comparable system possessing higher Rayleigh number. We discuss the implications of these results in light of the current inconsistencies between models and observations.
ADAPTIVE OPTICS IMAGING OF VHS 1256–1257: A LOW MASS COMPANION TO A BROWN DWARF BINARY SYSTEM
Authors: Stone Jordan M. , Skemer Andrew J. , Kratter Kaitlin M. , Dupuy Trent J. , Close Laird M. , Eisner Josh A. , Fortney Jonathan J. , Hinz Philip M. , Males Jared R. , Morley Caroline V. , Morzinski Katie M. , Ward-Duong Kimberly
Published: February 2016

Recently, Gauza et al. reported the discovery of a companion to the late M-dwarf, VHS J125601.92–125723.9 (VHS 1256–1257). The companion’s absolute photometry suggests its mass and atmosphere are similar to the HR 8799 planets. However, as a wide companion to a late-type star, it is more accessible to spectroscopic characterization. We discovered that the primary of this system is an equal-magnitude binary. For an age ∼300 Myr the A and B components each have a mass of

, and the b component has a mass of

, making VHS 1256–1257 only the third brown dwarf triple system. There exists some tension between the spectrophotometric distance of 17.2 ± 2.6 pc and the parallax distance of 12.7 ± 1.0 pc. At 12.7 pc VHS 1256–1257 A and B would be the faintest known M7.5 objects, and are even faint outliers among M8 types. If the larger spectrophotmetric distance is more accurate than the parallax, then the mass of each component increases. In particular, the mass of the b component increases well above the deuterium burning limit to

and the mass of each binary component increases to

. At 17.1 pc, the UVW kinematics of the system are consistent with membership in the AB Dor moving group. The architecture of the system resembles a hierarchical stellar multiple suggesting it formed via an extension of the star formation process to low masses. Continued astrometric monitoring will resolve this distance uncertainty and will provide dynamical masses for a new benchmark system.
Snake richness in urban forest fragments from Niterói and surroundings, state of Rio de Janeiro, southeastern Brazil
Authors: Citeli Nathalie , Hamdan Breno , Guedes Thais
Published: February 2016

The Atlantic Forest is a hotspot for biodiversity, an area which houses high species richness and endemism, but with high level of threat. With reference to the herpetofauna, until recently there has been no detailed information regarding diversity of snakes recorded in the Atlantic Forest, the number of endemic species and their distribution ranges. While these basic data were missing, large areas of original forest have continued to be lost to increased urbanization and human population, representing a severe threat to the biodiversity.

We recorded 28 snake species in our study area. Dipsadidae was the richest family with 14 species, followed by Colubridae (eight species), Boidae (two species), Viperidae (two species), and Anomalepididae, Elapidae and Typhlopidae (one species each). Most species were forest inhabitants (61%), of which 13 are endemic to the Atlantic Forest. There were no clearly defined species clusters regarding species composition. None of the species recorded in Niterói are listed as threatened in the Brazilian Redlist. However, most of them are strongly associated with forested areas and, perhaps, are not adapted to live in small fragments. Thus, more initiatives should be implemented to evaluate the true conservation status of these species in order to better protect them.
A new preparative method for simultaneous purification of ochratoxin A and ochratoxin B from wheat culture inoculated withAspergillus ochraceus
Authors: Zhao Z.Y. , Liu N. , Yang L.C. , Wu A.B. , Zhou Z.L. , Deng Y.F. , Song S.Q. , Wang J.H. , Hou J.F.
Published: February 2016

Ochratoxins are a mycotoxin family frequently found in agricultural commodities worldwide and pose a potential health risk to humans and animals. To obtain large amounts of high-purity ochratoxins for food safety monitoring and toxicological research, a novel and effective method was established for simultaneous purification of ochratoxin A (OTA) and ochratoxin B (OTB) from a wheat culture inoculated with an ochratoxin-producingAspergillus strain. The inoculated wheat culture was first extracted with methanol:water (80:20, v/v), followed by one or two cleanup procedures involving acid-assisted liquid-liquid extraction and gel permeation chromatography. Subsequently, target analytes were separated and collected using preparative high performance liquid chromatography. Finally, a combined approach of ultra-high performance liquid chromatography, ultraviolet spectrophotometry and mass spectrometry was applied for purity analysis and structural identification of the obtained toxins. As a result, 100 g of an inoculated wheat culture yielded 69 mg of OTA and 6 mg of OTB with purities greater than 98%. This proposed method might serve as a valuable reference to obtain expensive ochratoxin standards. To the best of our knowledge, this is the first report on simultaneous preparation of OTA and OTB from artificially inoculated wheat culture.
La demolición a gran escala como técnica de intervención urbana. La apertura de la Avenida de la Constitución de Sevilla (1906-1927)
Authors: Tejido Jiménez J.
Published: February 2016

La apertura de la Avenida de la Constitución de Sevilla es una intervención urbana del primer tercio del siglo XX, heredera de los planteamientos de Haussmann en París, y con semejanzas a la creación de la Gran Vía madrileña. Se realizó en un momento en el que aún no estaba formada la conciencia del valor patrimonial de los tejidos históricos, por lo que se basó en el borrado a gran escala de las tramas preexistentes. Su ejecución precisó, entre otras demoliciones, del derribo de dos edificios notables del siglo XVI, el antiguo Colegio de Santa María de Jesús –primera sede de la Universidad de Sevilla– y el antiguo Colegio dominico de Santo Tomás. Se confiaba en que la sección de la apertura y el porte de las nuevas arquitecturas que surgirían a continuación construirían la deseada Avenida, de la que todavía vive el acceso sur al centro monumental de Sevilla.
Sistemas de protección individual anticaídas sometidos a impacto. Simulaciones numéricas
Authors: Carrión E. A. , Irles R. , Segovia E. G. , Pomares J. C.
Published: February 2016

Los sistemas anticaída se establecen en UNE-EN-363 para evitar o retener caídas de personas sin que las fuerzas de retención causen daños relevantes. Constituyen el último recurso para prevención de caídas tras considerar otras medidas. Este artículo analiza las variables que afectan al comportamiento del sistema: altura de caída, longitud de cuerda de retención, rigidez y amortiguamiento del material de retención, y peso del operario. A tal fin, el fenómeno ha sido simulado con modelos dinámicos de elementos finitos mediante una cuerda elástica y un lastre rígido. Ello permite obtener valores verosímiles de las máximas fuerzas sobre el accidentado y el sistema durante el impacto. Los resultados demuestran el papel fundamental de la proporción entre altura de caída y longitud de cuerda (factor de caída), más determinante que la propia altura de caída. Las elevadas fuerzas máximas obtenidas indican la necesidad de incluir en el modelo absorbedores de energía elastoplásticos, en futuras investigaciones, con el fin de disminuir el impacto a valores razonables.
Composite cement mortars based on marine sediments and oyster shell powder
Authors: Ez-zaki H. , Diouri A. , Kamali-Bernard S. , Sassi O.
Published: February 2016

Additions of dredged marine sediments and oyster shell powder (OS) as cement substitute materials in mortars are examined by several techniques. The sediments have high water and chloride contents and calcite, quartz, illite and kaolinite as principal minerals. The OS powders are entirely composed of calcium carbonate and traces of other impurities. Four mixtures of treated sediments and OS powders at 650 °C and 850 °C are added to Portland cement at 8%, 16% and 33% by weight. The hydration of composite pastes is followed by calorimetric tests, the porosity accessible to water, the bulk density, the permeability to gas, the compressive strength and the accelerated carbonation resistance are measured. In general, the increase of addition amounts reduced the performance of mortars. However, a reduction of gas permeability was observed when the addition was up to 33%. Around 16% of addition, the compressive strength and carbonation resistance were improved.
Shrinkage behaviour and related corrosion performance of low-pH cementitious materials based on OPC or CAC
Authors: García-Calvo J. L. , Sánchez M. , Fernández-Luco L. , Alonso M. C.
Published: February 2016

Prior to using low-pH cementitious materials in underground repositories for high level waste, the characteristics determining their long-term durability must be analysed in depth. In this sense, different shrinkage tests have been made on mortar and concrete specimens using low-pH cement formulations based on ordinary portland cement (OPC) or calcium aluminate cement (CAC), with high mineral admixtures contents. They showed similar autogenous shrinkage than samples without mineral admixtures but higher drying shrinkage when materials based on OPC with high silica fume contents were considered. Besides, as the use of reinforced concrete could be required in underground repositories, the susceptibility of reinforcement to corrosion when using low-pH cementitious materials based on OPC was analyzed, considering carbon steel and galvanized steel. In the formers corrosion was detected due to the low pore solution pH but any problem was detected when galvanized reinforcement were used.
Retinoic Acid Receptor γ Regulates B and T Lymphopoiesis via Nestin-Expressing Cells in the Bone Marrow and Thymic Microenvironments
Authors: Joseph Chacko , Nota Celeste , Fletcher Jessica L. , Maluenda Ana C. , Green Alanna C. , Purton Louise E.
Published: February 2016

Vitamin A has essential but largely unexplained roles in regulating lymphopoiesis. We have previously shown that retinoic acid receptor (RAR) γ–deficient mice have hematopoietic defects, some phenotypes of which were microenvironment induced. Bone marrow (BM) microenvironment cells identified by either their expression of nestin (Nes) or osterix (Osx) have previously been shown to have roles in regulating lymphopoiesis. We therefore conditionally deleted Rarγ in Nes- or Osx-expressing microenvironment cells. Osx cell–specific deletion of Rarγ had no impact on hematopoiesis. In contrast, deletion of Rarγ in Nes-expressing cells resulted in reductions in peripheral blood B cells and CD4+ T cells, accompanied by reductions of immature PreB cells in BM. The mice lacking Rarγ in Nes-expressing cells also had smaller thymi, with reductions in double-negative 4 T cell precursors, accompanied by reduced numbers of both TCRβlow immature single-positive CD8+ cells and double-positive T cells. In the thymus, Nes expression was restricted to thymic stromal cells that expressed cerebellar degeneration-related Ag 1 and lacked expression of epithelial cell adhesion molecule. These cells expressed platelet-derived growth factor α and high transcript levels of Rars, Cxcl12, and stem cell factor (Scf). Short-term treatment of mice with all-trans retinoic acid resulted in increased PreB lymphopoiesis in BM and an increase in thymic double-negative 4 T cells, inverse to that observed upon Nes cell-specific deletion of Rarγ. Collectively, these studies show that RARγ is a regulator of B and T lymphopoiesis via Nes-expressing cells in the BM and thymic microenvironments, respectively.
GAPDH Binding to TNF-α mRNA Contributes to Posttranscriptional Repression in Monocytes: A Novel Mechanism of Communication between Inflammation and Metabolism
Authors: Millet Patrick , Vachharajani Vidula , McPhail Linda , Yoza Barbara , McCall Charles E.
Published: February 2016

Expression of the inflammatory cytokine TNF is tightly controlled. During endotoxin tolerance, transcription of TNF mRNA is repressed, although not entirely eliminated. Production of TNF cytokine, however, is further controlled by posttranscriptional regulation. In this study, we detail a mechanism of posttranscriptional repression of TNF mRNA by GAPDH binding to the TNF 3′ untranslated region. Using RNA immunoprecipitation, we demonstrate that GAPDH–TNF mRNA binding increases when THP-1 monocytes are in a low glycolysis state, and that this binding can be reversed by knocking down GAPDH expression or by increasing glycolysis. We show that reducing glycolysis decreases TNF mRNA association with polysomes. We demonstrate that GAPDH–TNF mRNA binding results in posttranscriptional repression of TNF and that the TNF mRNA 3′ untranslated region is sufficient for repression. Finally, after exploring this model in THP-1 cells, we demonstrate this mechanism affects TNF expression in primary human monocytes and macrophages. We conclude that GAPDH–TNF mRNA binding regulates expression of TNF based on cellular metabolic state. We think this mechanism has potentially significant implications for treatment of various immunometabolic conditions, including immune paralysis during septic shock.
Yin Yang 1 Promotes Thymocyte Survival by Downregulating p53
Authors: Chen Liang , Foreman Daniel P. , Sant’Angelo Derek B. , Krangel Michael S.
Published: February 2016

Yin Yang 1 (YY1) is a zinc finger protein that functions as a transcriptional activator or repressor and participates in multiple biological processes, including development and tumorigenesis. To investigate the role of YY1 in developing T cells, we used mouse models that depleted YY1 at two distinct stages of thymocyte development. When YY1 was depleted in CD4−CD8− double-negative thymocytes, development to the CD4+CD8+ double-positive stage was impaired, due to increased apoptosis that prevented expansion of post–β-selection thymocytes. When YY1 was depleted in double-positive thymocytes, they underwent increased cell-autonomous apoptosis in vitro and displayed a shorter lifespan in vivo, as judged by their ability to undergo secondary Vα-to-Jα recombination. Mechanistically, we found that the increased apoptosis in YY1-deficient thymocytes was attributed to overexpression of p53, because concurrent loss of p53 completely rescued the developmental defects of YY1-deficient thymocytes. These results indicated that YY1 functions as a critical regulator of thymocyte survival and that it does so by suppressing the expression of p53.
Resolvin D1 Dampens Pulmonary Inflammation and Promotes Clearance of Nontypeable Haemophilus influenzae
Authors: Croasdell Amanda , Lacy Shannon H. , Thatcher Thomas H. , Sime Patricia J. , Phipps Richard P.
Published: February 2016

Nontypeable Haemophilus influenzae (NTHi) is a Gram-negative, opportunistic pathogen that frequently causes ear infections, bronchitis, pneumonia, and exacerbations in patients with underlying inflammatory diseases, such as chronic obstructive pulmonary disease. In mice, NTHi is rapidly cleared, but a strong inflammatory response persists, underscoring the concept that NTHi induces dysregulation of normal inflammatory responses and causes a failure to resolve. Lipid-derived specialized proresolving mediators (SPMs) play a critical role in the active resolution of inflammation by both suppressing proinflammatory actions and promoting resolution pathways. Importantly, SPMs lack the immunosuppressive properties of classical anti-inflammatory therapies. On the basis of these characteristics, we hypothesized that aspirin-triggered resolvin D1 (AT-RvD1) would dampen NTHi-induced inflammation while still enhancing bacterial clearance. C57BL/6 mice were treated with AT-RvD1 and infected with live NTHi. AT-RvD1–treated mice had lower total cell counts and neutrophils in bronchoalveolar lavage fluid, and had earlier influx of macrophages. In addition, AT-RvD1–treated mice showed changes in temporal regulation of inflammatory cytokines and enzymes, with decreased KC at 6 h and decreased IL-6, TNF-α, and cyclooxygenase-2 expression at 24 h post infection. Despite reduced inflammation, AT-RvD1–treated mice had reduced NTHi bacterial load, mediated by enhanced clearance by macrophages and a skewing toward an M2 phenotype. Finally, AT-RvD1 protected NTHi-infected mice from weight loss, hypothermia, hypoxemia, and respiratory compromise. This research highlights the beneficial role of SPMs in pulmonary bacterial infections and provides the groundwork for further investigation into SPMs as alternatives to immunosuppressive therapies like steroids.