bluuebunny/crossref_metadata_2025 huggingface dataset:
Surviving Native β-Cells Determine Outcome of Syngeneic Intraportal Islet Transplantation
Authors: Hughes Stephen J. , Powis Stephen H. , Press Martin
Published: September 2018

In moderately diabetic rats (plasma glucose 20 – 30 mmol/L), where there is some residual pancreatic islet function, normoglycemia can be restored by transplantation of pancreatic islets into the liver via the portal vein. To examine whether normoglycemia can also be achieved in more severely diabetic animals (which more closely resemble human type I diabetes), we have compared the effect of transplanting 1000 islets intraportally in Lewis rats made moderately diabetic (55 mg/kg streptozotocin injected IP while nonfasting) or severely diabetic (65 mg/kg streptozotocin injected IP while fasting). In the moderately diabetic rats in which residual pancreatic insulin was 128 ± 40 mU insulin (2.0% of control), plasma glucose stabilized (32 ± 2.8 mmol/L at 1 week, 34 ± 2 mmol/L at 3 weeks) as did body weight (falling from 290 ± 5 to 265 ± 5 g at 1 week and 253 ± 6 g at 3 weeks). In contrast, in severely diabetic rats in which residual pancreatic insulin was only 13.5 ± 4.2 mU insulin (0.21% of control), there was a progressive rise in plasma glucose (30 ± 1.3 mmol/L at 1 week, 49 ± 4 mmol/L at 2 weeks, and 67 ± 7 mmol/L at 3 weeks) and a progressive fall in body weight (from 304 ± 10 to 260 ± 5 g by week 1 and to 209 ± 6 g by week 3). Following islet transplantation, nonfasting plasma glucose normalized in moderately diabetic rats (10.5 ± 0.6 vs. 9.1 ± 0.6 mmol/L in nondiabetic controls, NS) after 23 ± 5 days. In contrast, in the severely diabetic rats plasma glucose stabilized at 32 ± 5mmol/L (p < 0.05 compared to moderately diabetic group) but did not normalize. This difference was not attributable to different plasma glucose levels at the time of transplantation (35.1 ± 1.8 in moderately diabetic vs. 32.5 ± 2.5 mmol/L in severely diabetic rats). These observations demonstrate that residual native β-cells (equivalent to only 60 – 80 islets) contribute to the survival or function of intraportally transplanted islets.
Enhanced Survival of Grafts Genetically Endowed with the Ability to Block CD2 and B7
Authors: Brady Jamie L. , Yamashita Kenji , Lew Andrew M.
Published: September 2018

In a model of transplantation rejection, we have tested whether a graft manipulated to secrete immunomodulators could protect itself from immune destruction. An insulinoma cell line having the NOD genotype but also expressing the neoantigen, SV40 T antigen, was transfected with CTLA4Ig or LFA3Ig to block signals in the co-stimulatory/adhesion pathways. This neoantigen is potent at inducing graft rejection. Secretion of CTLA4Ig and LFA3Ig by transfectants promoted survival of the insulinoma graft in young NOD mice. In immunodeficient mice, cell growth was similar for all transfectants. However, in immunocompetent NOD mice the survival/growth of test grafts was significantly better than that of the controls. Graft survival was enhanced additively, when the two test transfectants were cotransplanted. Endowing the graft the ability to secrete immunomodulators that block individual co-stimulatory/adhesion signals can contribute to transplantation success. Blockade of two signals (CD2 and CD28) in these pathways enhances this success.
Posttranscriptional Mechanisms of Glucocorticoid Antiproliferative Effects: Glucocorticoids Inhibit IL-6-Induced Proliferation of B9 Hybridoma Cells
Authors: Almawi Wassim Y. , Tamim Hala
Published: September 2018

Addition of rIL-6 to IL-6-dependent B9 cells starved for IL-6 for 16 – 20 h stimulated a vigorous proliferative response. Glucocorticoids (GCs), in a concentration-dependent manner, inhibited rIL-6-stimulated proliferation of B9 cells This inhibition was specific for the GCs, evident by the capacity of the GCs, dexamethasone, prednisolone, and hydrocortisone, but not non-GC steroids, to suppress rIL-6-dependent B9 cell proliferation. Furthermore, GC inhibition of IL-6-stimulated B9 cell proliferation was receptor mediated and was abrogated by the GC receptor antagonist, RU486. In addition to their reported effects on inhibition IL-6 expression, the results presented support the notion that GCs also acted distally by suppressing signal transduction through the IL-6 receptor.
Transplantation of Human Neural Progenitor Cells to the Vitreous Cavity of the Royal College of Surgeons Rat
Authors: Mizumoto Hiroyuki , Mizumoto Keiko , Whiteley Simon J. O. , Shatos Marie , Klassen Henry , Young Michael J.
Published: September 2018

Human neural progenitor cells, originally isolated from prenatal donor tissue at 17 weeks of development, were cultured as neurospheres and transplanted to the vitreous cavity of dystrophic Royal College of Surgeons rats with, or without, cyclosporin A immunosuppression. Donor cells were either unlabeled or prelabeled, the latter utilizing incubation with BrdU or adenoviral modification to express green fluorescent protein. Recipients of various ages were examined at 1, 2, and 4 weeks postgrafting. Transplanted human neural progenitor cells survived in the host vitreous for at least 4 weeks and maintained expression of green fluorescent protein for at least 2 weeks. After 2 weeks in vivo, grafted cells differentiated morphologically, coincident with expression of the neuronal marker MAP, indicating mature neuronal differentiation. The extensive intraretinal migration previously shown using rat progenitor cells in the Royal College of Surgeons rat model was not seen in this experiment, suggesting that high levels of neuronal migration may depend at least in part upon species-specific molecular cues. Human neural progenitor cells represent a renewable source of multipotent human cells capable of in vivo neuronal development and a potential means of delivering therapeutic factors intraocularly. Human neural progenitor cells therefore provide a useful tool for studies of neural development and differentiation in the dystrophic eye.
Expansion of Hepatic and Hematopoietic Stem Cells Utilizing Mouse Embryonic Liver Explants
Authors: Monga Satdarshan P. S. , Tang Yi , Candotti Fabio , Rashid Asif , Wildner Oliver , Mishra Bibhuti , Iqbal Shareen , Mishra Lopa
Published: September 2018

Ex vivo embryonic liver explant culture is a novel and attractive approach to obtain abundant hepatic and hematopoietic stem cells. Gene therapy of autologous hepatic and hematopoietic stem cells represents an alternative therapeutic approach to liver transplantation for genetic and metabolic disorders. In this study we characterize the growth and differentiation of hepatic stem cells utilizing embryonic liver cultures. Day 9.5 liver buds are microdissected and cultured under specific conditions. Modulation of growth conditions by addition of hepatocyte growth factor, Flt-3 ligand, and stem cell factor leads to enrichment of hepatic progenitor cells in embryonic liver explants. Under these conditions, we also demonstrate the role of a novel marker PRAJA-1 to identify hepatic stem cells and transitional hepatocytes. Utilization of dexamethasone enhanced pseudolobule formation with increased hepatocytic and biliary differentiation. Transforming growth factor-β leads to enrichment of biliary cells in the culture. Gut formation is enhanced in the presence of interleukin-3 and blood formation by increasing the mesodermal tissue in these cultures. We also show increased retroviral-mediated expression of the green fluorescent protein expression in the expanded hepatic and hematopoietic stem cells under different culture conditions. Thus, the embryonic liver explant culture is an attractive source for hepatic progenitors and is a possible step towards generating nontumorigenic immortalized hepatocytes with possible transplantation applications.
Prolonged Postlesion Transplantation Delay Adversely Influences Survival of Both Homotopic and Heterotopic Fetal Hippocampal Cell Grafts in Kainate-Lesioned CA3 Region of Adult Hippocampus
Authors: Zaman Vandana , Turner Dennis A. , Shetty Ashok K.
Published: September 2018

Fetal hippocampal CA3 cell grafts exhibit dramatically enhanced survival when transplanted at an early postlesion delay of 4 days into the lesioned CA3 region of adult hippocampus. However, survival of these homotopic grafts following placement at late postlesion time points when the host milieu is considerably less receptive to grafts is unknown. We hypothesize that an extended postlesion delay at the time of grafting will lead to significant diminution in cell survival of both homotopic and heterotopic fetal transplants grafted to lesioned adult CNS. We quantitatively investigated absolute cell survival of 5′-bromodeoxyuridine-labeled fetal hippocampal CA3 and CA1 cell grafts, following transplantation into the lesioned CA3 region of adult rat hippocampus, at a delay of 45 days after a unilateral intracerebroventricular administration of kainic acid (KA). Survival of these grafts was also analyzed in intact CA3 of the hippocampus contralateral to KA administration for comparison. In lesioned CA3 region, CA3 (homotopic) and CA1 (heterotopic) grafts exhibited comparable but only moderate survival, with a recovery of only 21 – 31% of injected cells. Cell survival in these grafts into lesioned hippocampus was similar to survival of grafts placed into the contralateral intact CA3 region. These results are in sharp contrast to increased graft survival measured following transplants performed at 4 days postlesion. In such grafts placed early, there was both a significantly higher cell survival than grafts placed into the intact CA3 region and also a characteristic differential survival based on graft cell specificity to the lesioned CA3 region (Zaman et al., Exp. Neurol., 161:535 – 561, 2000). Thus, the enhanced conduciveness of lesioned CA3 region for survival of homotopic CA3 cell grafts observed at 4 days postlesion wanes by 45 days postlesion to that of intact CA3 region, in spite of residual loss of CA3 neurons with the lesion. Strategies that considerably augment graft cell survival may therefore be critical for optimal integration of fetal grafts into the adult CNS at late postlesion time points.
Adult Bone Marrow Transplantation after Stroke in Adult Rats
Authors: Li Yi , Chen Jieli , Chopp Michael
Published: September 2018

We transplanted adult whole bone marrow prelabeled with bromodeoxyuridine (BrdU) into the ischemic boundary zone of the adult rat brain at 1 day after 2 h of middle cerebral artery occlusion (MCAo). Approximately 3.3% of 106 transplanted bone marrow cells were BrdU reactive at 14 days after MCAo. BrdU-reactive cells expressed neuronal and astrocytic proteins, neuronal nuclei protein (NeuN, 1%), and glial fibrillary acidic protein (GFAP, 5%) immunoreactivities, respectively. In addition, bone marrow transplantation promoted proliferation of ependymal and subependymal cells, identified by nestin (a neuroepithelial stem cell marker), within the ventricular zone and subventricular zone (VZ/SVZ). These data suggest that intracerebral transplantation of bone marrow could potentially be used to induce plasticity in ischemic brain.
Normalization of Blood Glucose after Islet Cografting with Placental Tissues in Diabetic Mice
Authors: Suzuki Kazuhisa , Ueda Hiroo , Yokono Koichi , Taniguchi Hiroshi
Published: September 2018

A fetus in the uterus is not rejected at any time during the entire gestational period, even without the administration of immunosuppressive agents, though fetus is a kind of allograft. This prevention of rejection is considered to be associated with the presence of placental tissues. This hypothesis was tested by the allografting of islets together with placental tissues (trophoblasts) in streptozotocin (STZ)-induced diabetic mice. Placentae were harvested from the mice at the 14th postgestation day by being peeled off carefully and with the maternal decidua left behind, and cut into small pieces. Five hundred freshly isolated islets together with placental tissues obtained from ICR mice were placed under the left kidney capsule of STZ-induced diabetic C57BL/6J mice. The nonfasting blood glucose level was reduced from 477 ± 41 mg/dl at the time of pretransplant to that of the intact normal mice (161 ± 18 mg/dl) soon after the cografting, and did not return to the pretransplant level before the 14th posttransplant day. The grafting of the same number of islets alone and/or liver tissues dropped the blood glucose level, but not to that of the intact normal mice. It returned to the pretransplant level within 1 week. This is the first successful prolongation of survival of allografted islets without immunosuppressive agents through cotransplantation of allogenic placental tissues. The underlying mechanism remains to be clarified.
Enhanced In Vitro Maturation of Fetal Mouse Liver Cells with Oncostatin M, Nicotinamide, and Dimethyl Sulfoxide
Authors: Sakai Y. , Jiang J. , Kojima N. , Kinoshita T. , Miyajima A.
Published: September 2018

Although cells isolated from fetal liver are one of the major sources for liver tissue engineering, it is still very difficult to induce them to fully differentiate in vitro into mature hepatocytes. We therefore investigated the effects of nicotinamide (NA), dimethyl sulfoxide (DMSO), and oncostatin M (OSM) on differentiation in terms of the expression of various liver-specific functions, because these factors have been reported to induce the emergence of possible hepatocyte progenitor cells (small hepatocytes) in adult rat hepatocyte culture or maturation of fetal mouse liver cells in culture. Fetal liver cells isolated from mouse embryos were cultured for 5 weeks in collagen-precoated plates. NA (10 mM) and DMSO (1%) remarkably enhanced the emergence of small hepatocytes, and OSM also synergistically enhanced the selective growth of small hepatocytes and inhibited the growth of blood cell populations. In the presence of these three factors, such small hepatocytes became dominant in culture, so that they covered almost 60–70% of confluence after week 2. In addition, some of them piled up over the small hepatocyte monolayer and displayed distinctively differentiated morphology, such as the emergence of binucleated cells, formation of tight gap junctions, and possible bile duct structures. Although OSM alone had very weak effects on hepatocyte functions, albumin secretion and cytochrome P450IA1/2 capacity were greatly enhanced when combined with NA or DMSO. This functional observation closely agreed with the emergence of small hepatocytes. In contrast, ammonium removal was strongly dependent on DMSO alone. DNA amount basis functions of fetal cells with three factors at week 5 were 1/7 for albumin secretion, 3 times higher for ammonium removal, and 1/10 for P450 capacity, compared with those of cultured adult mouse hepatocytes. These results show that inclusion of NA, DMSO, and OSM in the culture medium significantly enhances in vitro maturation of fetal liver cells when compared with conventional culture conditions.
Microencapsulation of Cells Producing Therapeutic Proteins: Optimizing Cell Growth and Secretion
Authors: Rokstad Anne Mari , Holtan Synnøve , Strand Berit , Steinkjer Bjørg , Ryan Liv , Kulseng Bård , Skjåk-Bræk Gudmund , Espevik Terje
Published: September 2018

Microencapsulation of genetically engineered cells may have important applications as delivery systems for therapeutic proteins. However, optimization of the microcapsules with regard to mechanical stability, cell growth, and secretion of proteins is necessary in order to evaluate the future use of this delivery technology. We have explored the growth, survival, and secretion of therapeutic proteins from 293-EBNA cells producing endostatin (293 endo cells) and JJN3 myeloma cells producing hepatocyte growth factor (HGF) that have been embedded in various types of alginate capsules. Parameters that affect capsule integrity such as homogenous and inhomogenous gel cores and addition of an outer poly-l-lysine (PLL)–alginate coating were evaluated in relation to cell functions. When cells were encapsulated, the PLL layer was found to be absolutely required for the capsule integrity. The JJN3 and 293 endo cells displayed completely different growth and distribution patterns of live and dead cells within the microcapsules, as shown by 3D pictures reconstructed from images taken with confocal laser scanning microscopy (CLSM). Encapsulated JJN3 cells showed a bell-shaped growth and HGF secretion curve over a time period of 5 months. The 293 endo cells reached a plateau phase in growth after 23 days postencapsulation; however, after around 30 days a fraction of the microcapsules started to disintegrate. Microcapsule disintegration occurred with time irrespective of capsule and cell type, showing that alginate microcapsules possessing relatively high gel strength are not strong enough to keep proliferating cells within the microcapsules for prolonged time periods. Although this study shows that the stability of an alginate-based cell factory can be increased by a PLL–alginate coating, further improvement is necessary with regard to capsule integrity as well as controlling the cell growth before this technology can be used for therapy.
In Vivo Differentiation of Mouse Embryonic Stem Cells into Hepatocytes
Authors: Choi Dongho , Oh Hyun-Jeong , Chang Uck-Jin , Koo Soo Kyung , Jiang Jean X. , Hwang Sue-Yun , Lee Jung-Dal , Yeoh George C. , Shin Hee-Sup , Lee Jin-Sung , Oh Bermseok
Published: September 2018

Embryonic stem (ES) cells have been regarded as a powerful resource for cell replacement therapy. In recent reports mouse ES cells have been successfully applied in the treatment of spinal cord injury, hereditary myelin disorder of the central nervous system, and diabetes mellitus. Another type of disease that could benefit from the availability of stem cell therapy is liver disease. However, for this potential to be realized, it is necessary to demonstrate the differentiation of ES cells into hepatocytes. To demonstrate the in vivo differentiation potential of mouse ES cells, we injected ES cells into the spleen of immunosuppressed nude mice. Histological analysis of teratomas derived from injected ES cells revealed that some areas contained typical hepatocytes arranged in a sinusoidal structure. The hepatic nature of these cells was further confirmed by showing that transcripts of liver-specific genes were present in the differentiated teratoma using reverse transcriptase-polymerase chain reaction and immunohistochemistry using several liver-specific antibodies including HEP-PAR, phenylalanine hydroxylase, and mouse N-system aminotransferase to identify the respective proteins in the differentiated hepatocytes. This is the first demonstration that mouse ES cells can differentiate in vivo into a mixed population of hepatocytes of varying maturity. This finding extends the potential use of ES cells in the cell replacement therapy by including its possible application for treating liver diseases.
Effects of Caspase Inhibitors on Hematopoietic Engraftment after Short-Term Culture
Authors: Wiesmann Anne , Searles A. Elena , Pierce L. Jeanne , Spangrude Gerald J.
Published: September 2018

The induction of apoptosis during cytokine-induced proliferation of hematopoietic stem and progenitor cells (HSPC) may result in the loss of hematopoietic function. We tested the ability of several caspase inhibitors to maintain transplantation potential of mouse HSPC during in vitro culture. HSPC were isolated from mouse bone marrow by cell sorting and cultured in the presence of steel factor (STL) with or without various caspase inhibitors. After incubation, cells were harvested and tested for in vitro colony-forming cell (CFC) potential and transplantation activity in both short- and long-term in vivo assays. HSPC required STL to retain CFC activity during a 24-h culture at 37°C, and none of three caspase inhibitors could substitute for STL in this respect. In transplant assays, a twofold higher frequency of animals showed donor-derived blood cells 12 weeks after competitive transplantation of 50 HSPC cultured for 4 h in the presence of STL plus n-acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone (ac-YVAD) compared with 50 cells cultured in STL alone. To evaluate the effect of ac-YVAD on short-term engraftment, 500 cultured HSPC were transplanted into lethally irradiated mice. Animals transplanted with cells cultured in the presence of ac-YVAD showed a higher survival rate and a faster recovery of platelets and hematocrit compared with animals transplanted with cells cultured in STL alone. We conclude that both the short-term and the long-term engraftment potentials of HSPC cultured in the presence of STL + ac-YVAD were superior to that obtained from cells cultured in STL alone.
High Metabolic Function of Primary Human and Porcine Hepatocytes in a Polyurethane Foam/Spheroid Culture System in Plasma from Patients with Fulminant Hepatic Failure
Authors: Yamashita Yo-Ichi , Shimada Mitsuo , Tsujita Eiji , Shirabe Ken , Ijima Hiroyuki , Nakazawa Kohji , Sakiyama Ryoichi , Fukuda Junji , Funatsu Kazumori , Sugimachi Keizo
Published: September 2018

It has been demonstrated that plasma from patients with fulminant hepatic failure (FHF) interferes extensively with cellular function. We placed primary human and primary porcine hepatocytes in a polyurethane foam (PUF)/spheroid culture system and compared the metabolic functions in the plasma of patients with FHF in a 24-h stationary culture to those in a monolayer culture. The PUF/spheroid culture system using primary human and primary porcine hepatocytes significantly decreased ammonia content during 28-day culture. Fisher's ratio significantly increased at culture days 3 and 7. Tauroursodeoxycholic acid significantly increased and glycochenodeoxycholic acid and taurochenodeoxycholic acid decreased in the FHF patients' plasma at culture day 3. During at least a 24-h culture in the FHF patients' plasma, metabolic functions of primary human and primary porcine hepatocytes were almost identical. The present results indicate that the PUF/spheroid culture system using primary human or primary porcine hepatocytes demonstrated more advantageous metabolic functions in the plasma from patients with FHF than the monolayer culture.
Beneficial Effects of Hyperbaric Oxygen Therapy on Islet Transplantation
Authors: Juang Jyuhn-Huarng , Hsu Brend Ray-Sea , Kuo Chien-Hung , Ueng Steve Wen-Neng
Published: September 2018

We envisage that hyperbaric oxygen (HBO) would ameliorate islet anoxia, preventing early graft failure. Thus, treatment of HBO to diabetic recipients should improve the outcome of islet transplantation. We tested this hypothesis by syngeneically transplanting insufficient number of islets (150 islets) into streptozotocin-diabetic C57BL/6 mice, each followed by HBO (2.4 ATA, 100% O2) therapy for 1.5 h from day 0 to 28, once daily (group A) or twice daily (group B), or from day 5 to 28, once daily (group C) or twice daily (group D), 6 days/week. Recipients without HBO treatment served as controls. At day 28 after transplantation, groups B, C, and D gained weight and had lower blood glucose compared with their baseline values. In addition, groups B and D had higher insulin content of the graft than the controls. To determine the optimal timing of HBO therapy, groups B and D were compared with recipients treated with HBO twice daily, 6 days/week, from day –14 to 0 (group E) and from day –14 to 28 (group F). At day 28 after transplantation, groups B, D, E, and F had significantly lower blood glucose than their individual baseline values and higher insulin content of the graft than controls. But only group F had more β-cell mass of the graft than controls. These findings lend credence to the expectation that peritransplant application of adequate frequency of HBO to diabetic recipients would enhance the performance and growth of the islet graft, resulting in an improvement of the outcome of the transplantation.
Human Umbilical Cord Blood Cells Express Neural Antigens after Transplantation into the Developing Rat Brain
Authors: Zigova Tanja , Song Shijie , Willing Alison E. , Hudson Jennifer E. , Newman Mary B. , Saporta Samuel , Sanchez-Ramos Juan , Sanberg Paul R.
Published: September 2018

Recently, our laboratory began to characterize the mononuclear cells from human umbilical cord blood (HUCB) both in vitro and in vivo. These cryopreserved human cells are available in unlimited quantities and it is believed that they may represent a source of cells with possible therapeutic and practical value. Our previous molecular and immunocytochemical studies on cultured HUCB cells revealed their ability to respond to nerve growth factor (NGF) by increased expression of neural markers typical for nervous system-derived stem cells. In addition, the DNA microarray detected downregulation of several genes associated with development of blood cell lines. To further explore the survival and phenotypic properties of HUCB cells we transplanted them into the developing rat brain, which is known to provide a conducive environment for development of neural phenotypes. Prior to transplantation, HUCB cells were either cultured with DMEM and fetal bovine serum or were exposed to retinoic acid (RA) and nerve growth factor (NGF). Neonatal pups (1 day old) received unilateral injection of cell suspension into the anterior part of subventricular zone. One month after transplantation animals were perfused, their brains cryosectioned, and immunocytochemistry was performed for identification of neural phenotypes. Our results clearly demonstrated that approximately 20% of transplanted HUCB survived (without immunosuppression) within the neonatal brain. Additionally, double-labeling with cell-type-specific markers revealed that some HUCB-derived cells (recognized by anti-human nuclei labeling) were immunopositive for glial fibrillary acidic protein (GFAP) and few donor cells expressed the neuronal marker TuJ1 (class III β-tubulin). These findings suggest that at least some of the transplanted HUCB cells differentiated into cells with distinct glial or neuronal phenotypes after being exposed to instructive signals from the developing brain.
TrkC Overexpression Enhances Survival and Migration of Neural Stem Cell Transplants in the Rat Spinal Cord
Authors: Castellanos Daniel A. , Tsoulfas Pantelis , Frydel Beata R. , Gajavelli Shyam , Bes Jean-Claude , Sagen Jacqueline
Published: September 2018

Although CNS axons have the capacity to regenerate after spinal cord injury when provided with a permissive substrate, the lack of appropriate synaptic target sites for regenerating fibers may limit restoration of spinal circuitry. Studies in our laboratory are focused on utilizing neural stem cells to provide new synaptic target sites for regenerating spinal axons following injury. As an initial step, rat neural precursor cells genetically engineered to overexpress the tyrosine kinase C (trkC) neurotrophin receptor were transplanted into the intact rat spinal cord to evaluate their survival and differentiation. Cells were either pretreated in vitro prior to transplantation with trkC ligand neurotrophin-3 (NT-3) to initiate differentiation or exposed to NT-3 in vivo following transplantation via gelfoam or Oxycel©. Both treatments enhanced survival of trkC-overexpressing stem cells to nearly 100%, in comparison with approximately 30–50% when either NT-3 or trkC was omitted. In addition, increased migration of trkC-overexpressing cells throughout the spinal gray matter was noted, particularly following in vivo NT-3 exposure. The combined trkC expression and NT-3 treatment appeared to reduce astrocytic differentiation of transplanted neural precursors. Decreased cavitation and increased β-tubulin fibers were noted in the vicinity of transplanted cells, although the majority of transplanted cells appeared to remain in an undifferentiated state. These findings suggest that genetically engineered neural stem cells in combination with neurotrophin treatment may be a useful addition to strategies for repair of spinal neurocircuitry following injury.
Upregulation of EphA Receptor Expression in the Injured Adult Rat Spinal Cord
Authors: Willson Christopher A. , Irizarry-Ramírez Margarita , Gaskins Hope E. , Cruz-Orengo Lillian , Figueroa Johnny D. , Whittemore Scott R. , Miranda Jorge D.
Published: September 2018

After spinal cord injury (SCI), the inability of supraspinal neurons to regenerate or reform functional connections is likely due to proteins in the surrounding microenvironment restricting regeneration. EphAs are a family of receptor tyrosine kinases that are involved in axonal guidance during development. These receptors and their ligands, the Ephrins, act via repulsive mechanisms to guide growing axons towards their appropriate targets and allow for the correct developmental connections to be made. In the present study, we investigated whether EphA receptor expression changed after a thoracic contusion SCI. Our results indicate that several EphA molecules are upregulated after SCI. Using semiquantitative RT-PCR to investigate mRNA expression after SCI, we found that EphA3, A4, and A7 mRNAs were upregulated. EphA3, A4, A6, and A8 receptor immunoreactivity increased in the ventrolateral white matter (VWM) at the injury epicenter. EphA7 had the highest level of immunoreactivity in both control and injured rat spinal cord. EphA receptor expression in the white matter originated from glial cells as coexpression in both astrocytes and oligodendrocytes was observed. In contrast, gray matter expression was localized to neurons of the ventral gray matter (motor neurons) and dorsal horn. After SCI, specific EphA receptor subtypes are upregulated and these increases may create an environment that is unfavorable for neurite outgrowth and functional regeneration.
ZnO-nanostructure-based electrochemical sensor: Effect of nanostructure morphology on the sensing of heavy metal ions
Authors: Krasovska Marina , Gerbreders Vjaceslavs , Mihailova Irena , Ogurcovs Andrejs , Sledevskis Eriks , Gerbreders Andrejs , Sarajevs Pavels
Published: September 2018

ZnO nanostructures are promising candidates for use in sensors, especially in electrochemical sensors and biosensors, due to their unique physical and chemical properties, as well as sensitivity and selectivity to several types of contamination, including heavy metal ions. In this work, using the hydrothermal method, nanostructures of ZnO were synthesized in four different morphologies: nanorods, nanoneedles, nanotubes and nanoplates. To determine the peculiarities of adsorption for each morphology, a series of electrochemical measurements were carried out using these nanostructured ZnO coatings on the working electrodes, using aqueous solutions of Pb(NO3)2 and Cd(NO3)2 as analytes with different concentrations. It was found that the sensitivity of the resulting electrochemical sensors depends on the morphology of the ZnO nanostructures: the best results were achieved in the case of porous nanostructures (nanotubes and nanoplates), whereas the lowest sensitivity corresponded to ZnO nanorods with a large diameter (i.e., low surface-to-volume ratio). The efficiency of sedimentation is also related to the electronegativity of adsorbate: it has been shown that all observed ZnO morphologies exhibited significantly higher sensitivity in detecting lead ions compared to cadmium ions.
Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine
Authors: Pomarański Piotr , Roszkowski Piotr , Maurin Jan K , Budzianowski Armand , Czarnocki Zbigniew
Published: September 2018

Background: Atropisomers are very interesting stereoisomers having axial chirality resulting from restricted rotation around single bonds and are found in various classes of compounds. ortho-Substituted arylpyridines are an important group of them. A regio- and atropselective Suzuki–Miyaura cross-coupling reaction on 3,4,5-tribromo-2,6-dimethylpyridine was studied.

Results: Reactions with various amounts of ortho-substituted phenylboronic acids with 3,4,5-tribromo-2,6-dimethylpyridine gave a series of mono- di- and triarylpyridine derivatives which allowed to draw conclusions about the order of substitution. Also, the observed selectivity in the case of ortho-methoxyphenylboronic acid suggested an additional metal O-chelation effect in the transition state, apparently not present in the ortho-chloro analogues. The rotational barrier in selected atropisomers was determined on the basis of HT NMR and thermal epimerisation experiments. The structure of most presented atropisomeric derivatives of 2,6-dimethylpyridine was confirmed by single-crystal X-ray analysis. Racemic chiral, differently substituted atropisomers were also examined by 1H NMR spectroscopy in the presence of a chiral solvating agent.

Conclusion: This regio- and atropselectivity may be generally applicable to other arylpyridine systems. A regio- and atropselective Suzuki–Miyaura cross-coupling process has been observed, giving an efficient access to a class of atropisomeric compounds. An opposite selectivity using a differently ortho-substituted phenylbornic acid was observed.
The Potential Utility for Massage Therapy During Pregnancy to Decrease Stress and Tobacco Use
Authors: O’Hair, BA Cayla M. , Armstrong, MA, LMT Kathryn , Rutherford, PhD Helena J.V.
Published: September 2018

Background: A significant number of women continue to smoke tobacco during pregnancy despite the increased risk of complications to fetal and infant development. Therefore, effective interventions are needed to assist pregnant women with the process of tobacco cessation. Traditional counseling programs have demonstrated some success; however, novel approaches that target stressas a mechanism in the maintenance of addiction would be valuable.Objective: To examine the role of stress in addiction and the utility of massage therapy to decrease stress during pregnancy.Conclusion: Preliminary evidence suggests massage therapy may be beneficial to decreasing tobacco use, and research in pregnant populations is needed.
A SOLUTION OF SUBORDINATE VERTICES FOR QUALITY CONNECTIONS OF EXTERNAL FREE-FORM CONCRETE PANELS
Authors: Lim Jeeyoung , Son Seunghyun , Yeong Kim Do , Fitriani Heni , Kim Sunkuk
Published: September 2018

3D-designs of free-form buildings are developed using a computer due to difficulty of shape implementation. When producing free-form concrete panel (FCP) using materials such as GFRC (glass fiber reinforced concrete), engineers or manufacturers should precisely calculate the offset value or geometry of each member at the junction point of three or more FCPs before it is constructed. However, it is difficult to calculate offset geometry easily and quickly, and no research has been conducted on this topic. Therefore, the objective of this paper is to develop a solution of subordinate vertices for quality connections of external free-form concrete panels. The developed mathematical solutions practically support the production of FCPs with precise installation to ensure aesthetic quality of the building. This paper academically contributes to the automatic creation of joint details of FCPs implemented by BIM.
RadFil: A Python Package for Building and Fitting Radial Profiles for Interstellar Filaments
Authors: Zucker Catherine , Chen Hope How-Huan ,   (co-PIs)
Published: September 2018

We present RadFil, a publicly available Python package that gives users full control over how to build and fit radial profiles for interstellar filaments. RadFil builds filament profiles by taking radial cuts across the spine of a filament, thereby preserving the radial structure of the filament across its entire length. Pre-existing spines can be inputted directly into RadFil, or can be computed using the FilFinder package as part of the RadFil workflow. We provide Gaussian and Plummer built-in fitting functions, in addition to a background subtraction estimator, which can be fit to the entire ensemble of radial cuts or an average radial profile for the filament. Users can tweak parameters like the radial cut sampling interval, the background subtraction estimation radii, and the Gaussian/Plummer fitting radii. As a result, RadFil can provide treatment of how the resulting filament properties rely on systematics in the building and fitting process. We walk through the typical RadFil workflow and compare our results to those from an independent radial profile code obtained using the same data; we find that our results are entirely consistent. RadFil is open source and available on GitHub. We also provide a complete working tutorial of the code available as a Jupyter notebook, which users can download and run themselves.
Photochemical Processes in CO2/H2O Ice Mixtures with Trapped Pyrene, a Model Polycyclic Aromatic Hydrocarbon
Authors: Radhakrishnan Soumya , Gudipati Murthy S. , Sander Wolfram , Lignell Antti
Published: September 2018

Vacuum ultraviolet irradiation of a polycyclic aromatic hydrocarbon molecule, pyrene, trapped in carbon dioxide (CO2)-enriched astrophysical ice analogues has been studied and presented here. Pyrene is co-deposited with a gaseous mixture of H2O and CO2 (100% CO2; 50:50 CO2:H2O; and 100% H2O) and is subjected to Ly
α
photons from a hydrogen-flow microwave discharge lamp. To our surprise, we found ionization of pyrene in all three ices, with ionization yields following the H2O content in the ice, indicating that H2O ice stabilizes charged ions and electrons better than CO2 ice by a factor of 10. Caution needs to be exercised not to overinterpret our finding that pyrene is ionized in pure CO2 ice, because even trace amounts of water in the CO2 matrix could result in an increased ionization of pyrene. In addition to ionization of pyrene in CO2 ice, photochemical products of the CO2 ice itself, namely CO and CO3, were found to form efficiently, as detected using Fourier transform infrared spectroscopy, in agreement with earlier studies. UV–vis spectra showed formation of ozone (O3) with prolonged irradiation. Surprisingly, O3 yields followed CO2 concentration in the ice mixtures, with the strongest bands in photolyzed CO2 ice and the weakest in photolyzed H2O ice, indicating that CO2 ice is very protoreactive and produces more O atoms than H2O ice. Pyrene-containing photoproducts, incorporating CO2 or CO or O, such as Py-COOH, Py-OH, or Py-CHO, are not explicitly seen in the UV–vis absorption spectra, but we cannot rule out the possibility that their UV absorption may be swamped under the strong absorption of O3.
Quantitative Constraints on the Reionization History from the IGM Damping Wing Signature in Two Quasars at z > 7
Authors: Davies Frederick B. , Hennawi Joseph F. , Bañados Eduardo , Lukić Zarija , Decarli Roberto , Fan Xiaohui , Farina Emanuele P. , Mazzucchelli Chiara , Rix Hans-Walter , Venemans Bram P. , Walter Fabian , Wang Feige , Yang Jinyi
Published: September 2018

During reionization, neutral hydrogen in the intergalactic medium (IGM) imprints a damping wing absorption feature on the spectrum of high-redshift quasars. A detection of this signature provides compelling evidence for a significantly neutral universe, and enables measurements of the hydrogen neutral fraction x
H i
(z) at that epoch. Obtaining reliable quantitative constraints from this technique, however, is challenging due to stochasticity induced by the patchy inside-out topology of reionization, degeneracies with quasar lifetime, and the unknown unabsorbed quasar spectrum close to rest-frame Lyα. We combine a large-volume semi-numerical simulation of reionization topology with 1D radiative transfer through high-resolution hydrodynamical simulations of the high-redshift universe to construct models of quasar transmission spectra during reionization. Our state-of-the-art approach captures the distribution of damping wing strengths in biased quasar halos that should have reionized earlier, as well as the erosion of neutral gas in the quasar environment caused by its own ionizing radiation. Combining this detailed model with our new technique for predicting the quasar continuum and its associated uncertainty, we introduce a Bayesian statistical method to jointly constrain the neutral fraction of the universe and the quasar lifetime from individual quasar spectra. We apply this methodology to the spectra of the two quasars with the highest redshifts known, ULAS J1120+0641 and ULAS J1342+0928, and measure volume-averaged neutral fractions

and

(posterior medians and 68% credible intervals) when marginalized over quasar lifetimes of 103 ≤ t
q ≤ 108 yr.
The Age of the Old Metal-poor Globular Cluster NGC 6397 Using WFC3/IR Photometry*
Authors: Correnti Matteo , Gennaro Mario , Kalirai Jason S. , Cohen Roger E. , Brown Thomas M.
Published: September 2018

Globular clusters (GCs) in the Milky Way represent the ideal laboratory to establish the age of the oldest stellar populations and to measure the color–magnitude relation of stars. Infrared (IR) photometry of these objects provides a new opportunity to accomplish this task. In particular, at low stellar masses, the stellar main sequence (MS) in an IR color–magnitude diagram (CMD) exhibits a sharp “kink” (due to opacity effects in M dwarfs), such that lower mass and cooler dwarfs become bluer in the F110W − F160W color baseline and not redder. This inversion of the color–magnitude relation offers the possibility to fit GC properties using IR imaging, and to reduce their uncertainties. Here, we used the IR channel of the Wide Field Camera 3 on board the Hubble Space Telescope to obtain new, deep high-resolution photometry of the old metal-poor GC NGC 6397. From the analysis of the GC CMD, we revealed below the MS “kink” the presence of two MSs with different chemical compositions. We derived the cluster fiducial line and we compared it with a grid of isochrones over a large range of parameter space, allowing age, metallicity, distance, and reddening to vary freely within reasonable selected ranges. We derived an age of 12.6 Gyr with a random uncertainty σ ∼ 0.7 Gyr. These results confirm that the analysis of the IR color–magnitude of stars provide a valuable tool to measure the GC ages and offers a new venue to determine their absolute age to sub-Gyr accuracy with next generation IR telescopes.
Black Hole–Galaxy Scaling Relationships for Active Galactic Nuclei with Reverberation Masses
Authors: Bentz Misty C. , Manne-Nicholas Emily
Published: September 2018

We have utilized high-resolution optical Hubble Space Telescope images and deep, ground-based near-infrared images to examine the host galaxies of 37 active galactic nuclei (AGNs) with reverberation-based black hole masses. Using two-dimensional image decompositions, we have separated the host galaxy from the bright central AGN, allowing a re-examination of the

and

relationships and the

and

relationships using

color to constrain the stellar mass-to-light ratio. We find clear correlations for all of these scaling relationships, and the best-fit correlations are generally in good agreement with the sample of early-type galaxies with M
BH from dynamical modeling and the sample of megamasers. We also find good agreement with the expectations from the Illustris simulations, although the agreement with other simulations is less clear because of the different black hole mass ranges that are probed.

is found to have the least scatter, and is therefore the best predictor of M
BH among the relationships examined here. Large photometric surveys that rely on automated analysis and forego bulge-to-disk decompositions will achieve more accurate M
BH predictions if they rely on

rather than

. Finally, we have examined M
BH/M
stars and find a clear trend with black hole mass but not galaxy mass. This trend is also exhibited by galaxies with M
BH from dynamical modeling and megamaser galaxies, as well as simulated galaxies from Illustris, rising from ∼0.01% at 106
M
⊙ to ∼1.0% at 1010
M
⊙. This scaling should be taken into account when comparing galaxy samples that are not matched in M
BH.
An Unusual Energetic Particle Flux Enhancement Associated with Solar Wind Magnetic Island Dynamics
Authors: Zhao L.-L. , Zank G. P. , Khabarova O. , Du S. , Chen Y. , Adhikari L. , Hu Q.
Published: September 2018

The possibility that charged particles are accelerated statistically in a “sea” of small-scale interacting magnetic flux ropes in the supersonic solar wind is gaining credence. In this Letter, we extend the Zank et al. statistical transport theory for a nearly isotopic particle distribution by including an escape term corresponding to particle loss from a finite acceleration region. Steady-state 1D solutions for both the accelerated particle velocity distribution function and differential intensity are derived. We show Ulysses observations of an energetic particle flux enhancement event downstream of a shock near 5 au that is inconsistent with the predictions of classical diffusive shock acceleration (DSA) but may be explained by local acceleration associated with magnetic islands. An automated Grad-Shafranov reconstruction approach is employed to identify small-scale magnetic flux ropes behind the shock. For the first time, the observed energetic particle “time-intensity” profile and spectra are quantitatively compared with theoretical predictions. The results show that stochastic acceleration by interacting magnetic islands accounts successfully for the observed (i) peaking of particle intensities behind the shock instead of at the shock front as standard DSA predicts; (ii) increase in the particle flux amplification factor with increasing particle energy; (ii) increase in distance between the particle intensity peak and the shock front with increasing energy; and (iv) hardening of particle power-law spectra with increasing distance downstream of the shock.
Exploring the morphospace in subterranean spiders
Authors: Dejanaz Andrea , Mammola Stefano , Isaia Marco
Published: September 2018

In light of the reduced diversity and abundance of species, subterranean habitats represent ideal models systems in which to investigate characters displacement in species sharing the same habitat. In order to minimize direct competition, it is expected that sibling species occupying the same subterranean habitat should differentiate their morphological niche. Conversely, geographically vicariant species occupying similar microhabitats should display a convergent morphology. We tested these hypotheses by studying character displacement in different species of Troglohyphantes Joseph, 1881 spiders (Araneae: Linyphiidae) in the Western Italian Alps. These spiders underwent a remarkable radiations in subterranean habitats, with numerous stenoendemic elements showing different degrees of subterranean adaptation. For each considered species, we examined 10 to 15 females specimens for a number of morphological characters related to body size, degree of subterranean adaptation (eyes development, flattening of the cephalotorax and leg elongation) and trophic specialization (chelicera and fang length). These traits were combined in a multidimensional space in order to describe the geometry of the n-dimensional Hutchinsonian hypervolume representing the morphological niche of each species. Once the hypervolumes were constructed, pairwise similarity among each species niche was calculated using different overlap indexes. We found that the niche hypervolume of all Troglohyphantes species had a comparable size. However, the distance among niche centroids was lower for species with similar subterranean adaptation and significantly higher in coexisting species. Furthermore, when found in the same cave, species with similar degree of adaptation showed a limited niche overlap. Overall, our results highlight the key role of competition in shaping morphology when competing species are present.