bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioavailability of all-trans and cis–Isomers of Lycopene
Authors: Boileau Thomas W.-M. , Boileau Amy C. , Erdman John W.
Published: January 2017

Lycopene, the predominant carotenoid in tomatoes, is among the major carotenoids in serum and tissues of Americans. Although about 90% of the lycopene in dietary sources is found in the linear, all-trans conformation, human tissues contain mainly cis-isomers. Several research groups have suggested that cis-lsomers of lycopene are better absorbed than the all-trans form because of the shorter length of the cis-isomer, the greater solubility of cis-isomers in mixed micelles, and/or as a result of the lower tendency of cis-isomers to aggregate. Work with ferrets, a species that absorbs carotenoids intact, has demonstrated that whereas a lycopene dose, stomach, and Intestinal contents contained 6–18% cis-lycopene, the mesenteric lymph secretions contained 77%-cis isomers. The ferret studies support the hypotheses that cis-isomers are substantially more bioavailable then all-trans lycopene. In vitro studies suggest that cis-isomers are more soluble in bile acid micelles and may be preferentially incorporated into chylomicrons. The implications of these findings are not yet clear. Rats appear to accumulate lycopene in tissues within the ranges reported for humans, suggesting that they can be used to study effects of lycopene isomers on disease processes. Investigations are underway to determine whether there are biological differences between all-trans and various cis-isomers of lycopene regarding its antioxidant properties or other biological functions.
A Measure of Heart Rate Variability is Sensitive to Orthostatic Challenge in Women with Chronic Fatigue Syndrome
Authors: Yamamoto Yoshiharu , Lamanca John J. , Natelson Benjamin H.
Published: January 2017

The use of symptoms generated by head up tilt (HUT) is not a useful tool in identifying chronic fatigue syndrome (CFS). We investigated whether heart rate variability (HRV) assessed early during HUT might be useful. A sample of 46 female subjects (24 with CFS and 22 sedentary, age-matched healthy controls; CON) who had exhibited no difference in time to syncope during tilt was examined for HRV responses to 10 min of 70° HUT after 5 min of baseline in the supine position. HRV data were analyzed by the method of coarse graining spectral analysis. Variables compared between groups included mean and standard deviation (SDRRI) of RR intervals (RRI), amplitudes of low- (ALF; 0.04–0.15 Hz) and high-frequency (AHF; >0.15 Hz) harmonic as well as aperiodic, fractal (AFR; 1/fβ) spectral components, the spectral exponent β, and the difference in these values between baseline and HUT for each subject. In the supine baseline, only mean RRI was significantly (P< 0.01) lower in CFS than in CON. During HUT, however, mean RRI (P < 0.01), SDRRI, (P < 0.01), AHF (P < 0.05), and AFR (P < 0.01) were significantly lower in CFS than in CON. When the difference in values between baseline and HUT for each subject was examined, only the difference for AFR (ΔAFR) was significantly (P < 0.01) lower in CFS than in CON, suggesting that AFR is a disease-specific response of HRV to HUT. When a cut-off level was set to ΔAFR = –2.7 msec, the sensitivity and the specificity in differentiating CFS from controls were 90% and 72%, respectively. The data suggest that a decrease in aperiodic fractal component of HRV in response to HUT can be used to differentiate patients with CFS from CON.
Leptin Constrains Phospholipase C-Protein Kinase C-Induced Insulin Secretion via a Phosphatidylinositol 3-Kinase-Dependent Pathway
Authors: Lee Joo-Won , Swick Andrew G. , Romsos Dale R.
Published: January 2017

Leptin-deficient Lepob/Lepobmice hypersecrete insulin in response to acetylcholine stimulation of the phospholipase C-protein kinase C (PLC-PKC) pathway, and leptin constrains this hypersecretion. Leptin has been reported to activate phosphatidylinositol 3-kinase (PI 3-K) and subsequently phosphodiesterase (PDE) to impair protein kinase A (PKA)-induced insulin secretion from cultured islets of neonatal rats. We determined if PKA-induced insulin secretion was also hyperresponsive in Islets from Lepob/Lepobmice, and if leptin impaired this pathway in islets from these mice. Additionally, the possible role for PI 3-K and PDE in leptin-induced control of acetylcholine-induced insulin secretion was examined. Stimulation of Insulin secretion with GLP-1, forskolin (an activator of adenylyl cyclase), or IBMX (an inhibitor of PDE) did not cause hypersecretion of insulin from islets of young Lepob/Lepobmice, and leptin did not inhibit GLP-1-induced insulin secretion from islets of these mice. Inhibition of PDE with IBMX also did not block leptin-induced inhibition of acetylcholine-mediated insulin secretion from islets of Lepob/Lepobmice. But, preincubation of islets with wortmannin, an Inhibitor of PI 3-K activity, blocked the ability of leptin to constrain acetylcholine-induced insulin secretion from islets of Lepob/Lepobmice. We conclude that the capacity of the PKA pathway to stimulate insulin secretion is not increased in islets from young Lepob/Lepobmice, and that leptin does not regulate this pathway in islets from mice. Leptin may stimulate PI 3-K to constrain PLC-PKC-induced insulin secretion from Islets of Lepob/Lepobmice.
Enlargement of Interscapular Brown Adipose Tissue in Growth Hormone Antagonist Transgenic and in Growth Hormone Receptor Gene-Disrupted Dwarf Mice
Authors: Li Yuesheng , Knapp Joanne R. , Kopchick John J.
Published: January 2017

Growth hormone (GH) acts on adipose tissue by accelerating fat expenditure, preventing triglyceride accumulation, and facilitating lipid mobilization. To investigate whether GH is involved in the development and metabolism of interscapular brown adipose tissue (BAT), a site of nonshivering thermogenesis, we employed three lines of transgenic mice. Two of the lines are dwarf due to expression of a GH antagonist (GHA) or disruption of the GH receptor/binding-protein gene. A third mouse line is giant due to overexpression of a bovine GH (bGH) transgene. We have found that the body weights of those animals are proportional to their body lengths at 10 weeks of age. However, GHA dwarf mice tend to catch up with the nontransgenic (NT) littermates in body weight but not in body length at 52 weeks of age. The increase of body mass index (BMI) for GHA mice accelerates rapidly relative to controls as a function of age. We have also observed that BAT in both dwarf mouse lines but not in giant mice is enlarged in contrast to nontransgenic littermates. This enlargement occurs as a function of age. Northern analysis suggests that BAT can be a GH-responsive tissue because GHR/BP mRNAs were found there. Finally, the level of uncoupling protein-1 (UCP1) RNA was found to be higher in dwarf mice and lower in giant animals relative to controls, suggesting that GH-mediated signaling may negatively regulate UCP1 gene expression in BAT.
Leptin Receptor-Deficient MMTV-TGF-α/Leprdb Leprdb Female Mice Do Not Develop Oncogene-Induced Mammary Tumors
Authors: Cleary Margot P. , Juneja Subhash C. , Phillips Frederick C. , Hu Xin , Grande Joseph P. , Maihle Nita J.
Published: January 2017

Being overweight is a risk factor for postmenopausal breast cancer and is associated with an increased incidence and shortened latency of spontaneous and chemically Induced mammary tumors in rodents. However, leptin-deficient obese Lepob Lepob female mice have reduced incidences of spontaneous and oncogene-induced mammary tumors. Of interest, leptin enhances the proliferation of human breast cancer cell lines in which leptin receptors are expressed, which suggests that leptin signaling plays a role in tumor development. We evaluated oncogene-induced mammary tumor development in obese MMTV-TGF-α/Leprdb Leprdb mice that exhibit a defect in OB-Rb, which is considered to be the major signaling isoform of the leptin receptor. Lepr and MMTV-TGF-α mice were crossed, and the offspring were genotyped for oncogene expression and the determination of Lepr status. Lean MMTV-TGF-α/Lepr+ Lepr+ (homozygous) and MMTV-TGF-α/Lepr+ Leprdb (heterozygous) mice and obese MMTV-TGF-α/Leprdb Leprdb mice were monitored until age 104 weeks. Body weights of MMTV-TGF-α/Leprdb Leprdb mice were significantly heavier than those of the lean groups. No mammary tumors were detected in MMTV-TGF-α/LeprdbLeprdb mice, whereas the incidence of mammary tumors in MMTV-TGF-α/Lepr+ Lepr+ and MMTV-TGF-α/Lepr+ Leprdb mice was 69% and 82%, respectively. Examination of mammary tissue whole mounts indicated an absence of duct formation and branching for MMTV-TGF-α/Leprdb Leprdb mice. Both age at mammary tumor detection and tumor burden (tumors/mouse and tumor weights) were similar for the lean genotypes. Serum leptin levels of MMTV-TGF-α/Leprdb Leprdb mice were 12-20-fold higher than levels of lean mice. Thus, despite elevated serum leptin levels, leptin receptor-deficient MMTV-TGF-α/Leprdb Leprdb mice do not develop mammary tumors. This study provides additional evidence that leptin and its cognate receptor may be involved in mammary tumorigenesis.
Characterization of N-Terminal Interferon τ Mutants: P26L Affords Enhanced Activity and Lack of Toxicity
Authors: Shorts Lynnette H. , Dancz Christina E. , Shupp Jeffrey W. , Pontzer Carol H.
Published: January 2017

Interferon (IFN)-τ is a type I IFN that is responsible for the maternal recognition of pregnancy in ruminants. This protein also has classic IFN-like properties, including antiviral, antiproliferative, and immunomodulatory functions. Using IFN-τ as a model, we examined the structural basis for the activity of type I IFNs, focusing on amino acids within helix A and the first section of the AB loop, which have been proposed as a site for receptor interaction. Six amino-acid substitutions were made that replaced a residue in ovine IFN-τ1 mod with the corresponding residue in human IFN-αA. Receptor binding was enhanced by a P26L mutation and was reduced by a conservative lysine-to-histidine substitution at residue 34. Alterations in the antiviral and antiproliferative activities of the IFN- τ mutants were not always correlated, but both functions were maintained or enhanced relative to the wild-type IFN-τ by the proline-to-leucine mutation at residue 26. In contrast, this mutation did not affect the low in vitro cytotoxicity that is characteristic of ovine IFN-τ1 mod. Thus, the IFN- τ P26L mutant may have potential as an improved IFN-based therapeutic.
Molecular Machinery and Mechanism of Cell Secretion
Authors: Jena Bhanu P.
Published: January 2017

Secretion occurs in all living cells and involves the delivery of intracellular products to the cell exterior. Secretory products are Packaged and stored in membranous sacs or vesicles within the cell. When the cell needs to secrete these products, the secretory vesicles containing them dock and fuse at plasma membrane-associated supramolecular structures, called poro-somes, to release their contents. Specialized cells for neurotransmission, enzyme secretion, or hormone release use a highly regulated secretory process. Similar to other fundamen-tal cellular processes, cell secretion is precisely regulated. During secretion, swelling of secretory vesicles results in a build-up of intravesicular pressure, allowing expulsion of vesicular contents. The extent of vesicle swelling dictates the amount of vesicular contents expelled. The discovery of the Porosome as the universal secretory machinery, its isolation, its structure and dynamics at nanometer resolution and in real time, and its biochemical composition and functional reconstitution into artificial lipid membrane have been determined. The Molecular mechanism of secretory vesicle swelling and the fusion of opposing bilayers, that is, the fusion of secretory vesicle membrane at the base of the porosome membrane, have also been resolved. These findings reveal, for the first time, the universal molecular machinery and mechanism of secretion in cells.
Acute Versus Chronic Effects of Whey Proteins on Calcium Absorption in Growing Rats
Authors: Zhao Yongdong , Martin Berdine R. , Wastney Meryl E. , Schollum Linda , Weaver Connie M.
Published: January 2017

The acute and chronic effects of whey proteins on calcium metabolism and bone were evaluated. In acute studies, 8-week-old male rats were gavaged with 50 mg whey protein concentrate (WPC) and 25 mg calcium. 45Ca was administered intravenously or orally. Kinetic studies were performed, and femurs were harvested. Four of seven WPCs significantly increased femur uptake of 45Ca compared with controls. One WPC at 50 mg enhanced calcium absorption over a range of calcium Intakes from 35.1 ± 9.4% to 42.4 ± 14.0% (P < 0.01). Three of the most effective WPCs were tested further in a chronic feeding study. One hundred 3-week-old rats were randomly divided into four adequate dietary calcium (ADC; 0.4% Ca) groups (control of 20% casein and three WPC groups with 1% substitution of casein with each of three WPCs) and two low calcium (LC; 0.2% Ca) groups (control of 20% casein and one WPC group with 1% substitution of casein with one WPC). After 8 weeks, there was no effect of WPCs on femur uptake of 45Ca among ADC groups and there was no effect of WPCs on calcium retention, femur breaking force, femur bone mineral density, or total femur calcium at either dietary calcium intake. However, whole body bone mineral content (BMC) was significantly higher (P < 0.05) in the three whey protein concentrate ADC groups compared with the ADC control group. Total BMC at the proximal tibia in whey protein ADC groups was increased, as shown by peripheral quantitative computed tomography. Our results indicate that the acute calcium absorption–enhancing effect of whey proteins did not persist through long-term feeding in rats. However, the initial enhancement of calcium absorption by whey protein was sufficient to Increase BMC.
The Cross Talk Between Protein Kinase A– and RhoA-Mediated Signaling in Cancer Cells
Authors: Chen Yongchang , Wang Ying , Yu Hao , Wang Fengwei , Xu Wenrong
Published: January 2017

The cross talk between cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and RhoA-mediated signal transductions and the effect of this cross talk on biologic features of human prostate and gastric cancer cells were investigated. In the human gastric cancer cell line, SGC-7901, lysophosphatidic acid (LPA) increased RhoA activity in a dosedependent manner. The cellular permeable cAMP analog, 8-chlorophenylthio-cAMP (CPT-cAMP), inhibited the LPA-induced RhoA activation and caused phosphorylation of RhoA at serine188. Immunofluorescence microscopy, Western blotting, and green fluorescent protein (GFP)-tagged RhoA location assay in live cells revealed that RhoA was distributed in both the cytoplasm and nucleus of SGC-7901 cells. Treatment with LPA and/or CPT-cAMP did not induce obvious translocation of RhoA in the cells. The LPA treatment caused formation of F-actin in SGC-7901 cells, and CPT-cAMP inhibited the formation. In a modified Boyden chamber assay, LPA stimulated the migration of SGC-7901 cells, and CPT-cAMP dose-dependently inhibited the stimulating effect of LPA. In soft agar assay, LPA stimulated early proliferation of SGC-7901 cells, and CPT-cAMP significantly inhibited the growth of LPA-stimulated cells. In the prostate cancer cell line, PC-3, LPA caused morphologic changes from polygonal to round, and transfection with plasmid DNA encoding constitutively active RhoA(63L) caused a similar change. Treatment with CPT-cAMP inhibited the changes in both cases. However, in PC-3 cells transfected with a plasmid encoding mutant RhoA188A, LPA induced rounding, but CPT-cAMP could not prevent the change. Results of this experiment indicated that cAMP/PKA inhibited RhoA activation, and serine188phosphorylation on RhoA was necessary for PKA to exert its inhibitory effect on RhoA activation. The cross talk between cAMP/PKA and RhoA-mediated signal transductions had significant affect on biologic features of gastric and prostate cancer cells, such as morphologic and cytoskeletal change, migration, and anchorage-independent growth. The results may be helpful in implementing novel therapeutic strategies for invasive and metastatic prostate and gastric cancers.
Estrogen Regulation of the Rat Anterior Pituitary Gland Proteome
Authors: Blake Charles A. , Brown Lewis M. , Duncan Mark W. , Hunsucker Stephen W. , Helmke Steve M.
Published: January 2017

Estrogen Is known to affect the regulation of all six of the established anterior pituitary gland (AP) hormones, but little is known of the specifics of its regulation of the AP hormones, their isoforms, and nonhormonal AP proteins. We used difference gel electrophoresis in conjunction with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and peptide mass fingerprinting to quantify the effects of estrogen on the AP-soluble protein fraction in rats. Two-month-old rats were ovariectomized and used at 6 months of age. They were injected subcutaneously with sesame oil vehicle or 50 μg estradiol valerate in vehicle and studied 48 hrs later, approximately 3 hrs before the time of the anticipated onset of the estrogen-induced surges of gonadotropins in blood. The APs were pooled, and the soluble protein fraction was examined in replicate analyses. After DeCyder software analysis, we identified 26 protein spots that had a 1.5-fold or greater average increase in the experimental group relative to the controls. Nineteen showed a 1.5-fold or greater decrease. Estrogen increased levels of the more acidic isoforms of growth hormone and prolactin and of proteins involved in protein synthesis, folding, and secretion (e.g., eukaryotic translation elongation factor 2, ERp57, ERp29, Hsc70-ps1, calreticulin, coatomer delta subunit, and secretogranin II) and of some metabolic enzymes (e.g., arginosuccinate synthetase, enolase 1, creatine kinase B, phosphoglycerate mutase, malate dehydrogenase, pyruvate kinase, and aldolase A). The majority of the downregulated proteins were involved in RNA or DNA interactions (e.g., five heterogeneous nuclear ribonucleoproteins, DEAD-box proteins 17 and 48, ssDNA binding protein PUR-alpha, PTB-associated splicing factor, and Pigpen protein), but isovaleryl coenzyme A dehydrogenase, mitochondrial aldehyde dehydrogenase, stathmin 1, vinculin, radixin, and secretogranin III were also reduced. Our results indicate that estrogen acts in vivo within 48 hrs to modulate levels of a significant number of AP proteins.
Ovarian Aging and Menopause: Current Theories, Hypotheses, and Research Models
Authors: Wu Julie M. , Zelinski Mary B. , Ingram Donald K. , Ottinger Mary Ann
Published: January 2017

Aging of the reproductive system has been studied in numerous vertebrate species. Although there are wide variations in reproductive strategies and hormone cycle components, many of the fundamental changes that occur during aging are similar. Evolutionary hypotheses attempt to explain why menopause occurs, whereas cellular hypotheses attempt to explain how it occurs. It is commonly believed that a disruption in the hypothalamic-pituitary-gonadal axis Is responsible for the onset of menopause. Data exist to demonstrate that the first signs of menopause occur at the level of the brain or the ovary. Thus, finding an appropriate and representative animal model is especially important for the advancement of menopause research. In primates, there Is a gradual decline in the function of the hypothalamic-pituitary-gonadal (HPG) axis ultimately resulting in irregularities in menstrual cycles and increasingly sporadic incidence of ovulation. Rodents also exhibit a progressive deterioration in HPG axis function; however, they also experience a period of constant estrus accompanied by intermittent ovulations, reduced progesterone levels, and elevated circulating estradiol levels. It is remarkable to observe that females of other classes also demonstrate deterioration in HPG axis function and ovarian failure. Comparisons of aging in various taxa provide insight into fundamental biological mechanisms of aging that could underlie reproductive decline.
Tissue Distribution of Fetal Liver Cells Following in Utero Transplantation in Mice
Authors: Suckow Mark A. , Zollman Amy , Cornelissen Ivo , Casad Michelle , Roahrig Julie , Castellino Francis J. , Rosen Elliot D.
Published: January 2017

Transplantation of hepatic stem cells in utero has been advanced as a potential clinical approach to a variety of diseases, including deficiencies of coagulation factors. Although syngeneic transplantation has met with some success, consideration needs to be given to the potential for transplanted cells to colonize nontarget tissues. Liver cells were harvested from Rosa26 embyros at embryonic age 12.5 days postconception (pc) and transplanted into the peritoneal cavity of syngeneic recipients in utero. Tissues were harvested from tissue recipients at various time points ranging from 1 to 328 days pc, and tissues were stained for β-galactosidase to identify the existence of cells derived from Rosa26 donors, β-galactosidase-positive cells were found in the lung, liver, and brain as early as 20 days pc and through 328 days pc. Positive cells in these tissues existed as islands of cells that were morphologically similar to hepatocytes. In the spleen, individual β-galactosidase-positive cells of both leukocytic and erythrocytic lineages were present, and suggest that hematopoietic cells were transferred to recipients along with hepatocytes. The lack of an inflammatory response to the β-galactosidase-positive tells suggests that the donor cells were immunologically tolerated. In summary, the possibility that cells administered in utero may inadvertently colonize nontarget tissues suggests that clinical application of this method will need to be approached with diligence.
Effect of Soluble Nickel on Cellular Energy Metabolism in A549 Cells
Authors: Chen Haobin , Costa Max
Published: January 2017

Iron is an essential nutrient to most organisms, and is actively involved in oxygen delivery, electron transport, DNA synthesis, and many other biochemical reactions important for cell survival. We previously reported that nickel (Ni) ion exposure decreases cellular iron level and converts cytosolic aconitase (c-aconitase) to iron-regulatory proteln-1 in A549 cells (Chen H, Davidson T, Singleton S, Garrick MD, Costa M. Toxicol Appl Pharmacol 206:275–287, 2005). Here, we further investigated the effect of Ni ion exposure on the activity of mitochondrial iron-sulfur (Fe-S) enzymes and cellular energy metabolism. We found that acute Ni Ion treatment up to 1 mM exhibits minimal toxicity in A549 cells. Ni ion treatment decreases the activity of several Fe-S enzymes related to cellular energy metabolism, including mitochondrial aconitase (m-aconitase), succinate dehydrogenase (SDH), and NADH:ublquinone oxldoreductase (complex I). Low doses of Ni ion for 4 weeks resulted in an increased cellular glycolysis and NADH to NAD+ (NADH/NAD+) ratio, although glycolysis was inhibited at higher levels. Collectively, our results show that Ni Ions decrease the activity of cellular iron (Fe)-containing enzymes, Inhibit oxidative phosphorylation (OxPhos), and increase cellular glycolytic activity. Since increased glycolysis is one of the fundamental alterations of energy metabolism in cancer cells (the Warburg effect), the inhibition of Fe-S enzymes and subsequent changes in cellular energy metabolism caused by Ni Ions may play an Important role in Ni carcinogenesis.
Metals in Motor Neuron Diseases
Authors: Roos Per M. , Vesterberg Olof , Nordberg Monica
Published: January 2017

Degenerative processes within the nervous system are common features in disease entities such as dementia of Alzheimer type (DAT), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS). ALS is a neurodegenerative disease with unknown etiology; widespread muscle wasting and respiratory failure lead to death within a few years. Denervation can be detected with electromyography and axonal deterioration monitored by motor unit number estimates. Several suggestions about the cause of ALS have emerged but no solid theory has yet precipitated. Lead or mercury exposure has been suggested. Exposure data alone cannot support this connection. Alterations in metal kinetics may underlie the deterioration of motor function observed in patients with ALS. In this review the role of metals in motor neuron disease is discussed. Both classic studies on exposure and recent understanding of metal binding proteins are considered. Aspects of peak exposure and excretion are merged toward an understanding of metal dynamics in ALS. An overview of chemical and electrophysiological Investigations is given in the context of neurodegeneration.
Metallothionein as a Prognostic Biomarker in Breast Cancer
Authors: Bay Boon-Huat , Jin Rongxian , Huang Jingxiang , Tan Puay-Hoon
Published: January 2017

Breast cancer is the most common cancer in women, with a general upward trend in incidence. Basic and clinical breast cancer research has continued at a rapid pace, in the endeavor to understand the biology of the disease so as to improve management of patients. Besides traditional pathological indicators, expression of molecular markers in breast cancer has also been comprehensively investigated. This paper will focus on the prognostic utility of metallothioneins (MTs), a family of low molecular weight metal binding proteins encoded by at least 10 functional MT genes that are associated with cell proliferation in breast cancer. Evidence that MT is a potential prognostic biomarker for breast cancer is supported by many reports in the literature. Expression of the MT protein has been detected by immunohistochemistry in a significant portion of invasive ductal breast cancers. MT expression has also been well studied in association with traditional clinico-pathological parameters of breast cancers. Generally, higher MT expression in breast cancers is predictive of worse patient outcomes. The relationship of MT isoforms to histological grade, estrogen receptor (ER) status, and prognosis will also be discussed.
The Zn- and Cd-Clusters of Recombinant Mammalian MT1 and MT4 Metallothionein Domains Include Sulfide Ligands
Authors: Tío Laura , Villarreal Laura , Atrian Sílvia , Capdevila Mercè
Published: January 2017

Recombinant (E. coll) synthesis of mammalian MT1 and MT4 domains as separate peptides in Zn(II) and Cd(II) enriched growth media has rendered metal complexes containing sulfide anions as additional ligands. The Cd preparations show higher sulfide content than the Zn preparations. Also, the βMT1 and βMT4 fragments exhibit higher sulfide/peptide ratios than the respective α fragments. Titration of Zn3-βMT1 with Cd(II) followed by addition of several sodium sulfide equivalents shows that the Cd(II)-βMT1 species can incorporate sulfide ligands in vitro, with a concomitant evolution of their UV-vis and CD fingerprints to those characteristic of the Cd-S2- chromophores. Current results have also provided full understanding of previous data collected by this group in the characterization of the Cd-βMT1 preparations obtained from large-scale fermentor synthesis by allowing identification of at least 2S2- ligands per Cd-βMT1 species. Furthermore, the results here presented have revealed that synthesis of βMT4 in Cd-supplemented cultures yielded Cd,S2--containing clusters instead of the proposed heterometallic Zn, Cd-βMT4 complexes. Finally, a global evaluation of our results suggests that the higher the Cu-thionein character of a MT peptide, the higher is its tendency to harbor nonproteic ligands (i.e., sulfide anions) when building divalent metal clusters, especially Cd-MT complexes.
Cytotoxicity of Nitric Oxide Is Alleviated by Zinc-Mediated Expression of Antioxidant Genes
Authors: Chung Mi Ja , Hogstrand Christer , Lee Sung-Joon
Published: January 2017

Metallothioneins (MTs) are small, cysteine-rich zinc binding proteins that are powerful antioxidants. In this study, we investigated the interaction between zinc, MTs, and other components of the antioxidant defense system in HepG2 cells. Cells were preincubated with zinc and then exposed to sodium nitroprusslde (SNP), a nitric oxide (NO) donor. Both zinc pretreatment and SNP exposure separately induced transcription of MT genes (MT1A, MT2A, MT1E, MT1X), as measured using real time–polymerase chain reaction (PCR) after reverse transcription (RT). Pretreatment of HepG2 cells with zinc sulfate (ZnSO4) followed by SNP exposure caused MT and glucose-6-phosphate dehydrogenase (G6PD) mRNA levels to increase more than in cells only exposed to SNP. However, when cells were incubated with N,N,N′,N′-tetrakis(2-pyridylmethyl)ethyl-enediamine (TPEN), a membrane-permeant Zn2+ chelator, the stimulation of MT transcription by SNP was blocked, suggesting that SNP-induced upregulation of these genes is zinc-dependent. Human glutathione-S-transferase (hGSTA1) and G6PD mRNA levels in the cells treated with 5 μM TPEN decreased. Additionally, the induction of MT by SNP after zinc pretreatment appears to be mediated by metal-activated transcription factor-1 (MTF-1), which is induced by labile zinc in the cytosol. SNP cytotoxicity was inhibited by preincubation with zinc. Taken together, these results suggest that NO plays an important role in regulation of cellular zinc homeostasis and that NO-mediated release of protein-bound Zn2+ may be an important signal in antioxidant defense.
Transition from Academia to Industry: A Personal Account
Authors: Love Ted Wendell
Published: January 2017

A career in industry has become a widely accepted alternative for those of us trained in medicine and/or science who have traditionally focused on careers in academia. Like any career decision, consideration of a position in industry should include asking yourself a series of fundamental questions. A few of the key questions should include: 1) What kind of work environment do you find most enjoyable (e.g., patient care setting, basic research lab, team-oriented setting)?; 2) What are you focused on accomplishing in your career (basic research discoveries, contributions to clinical medicine, compensation)?; 3) Are you team oriented in your interactions or are you more of an Individual contributor? A successful career in any endeavor, including industry, starts with a careful and honest examination of what you are best suited for and inspired to do.
Effective Partnering of Academic and Physician Scientists with the Pharmaceutical Drug Development Industry
Authors: Kennedy Scott P. , Bormann B. J.
Published: January 2017

This manuscript briefly addresses the drug discovery and development process. It is a long road from the formulation of a good discovery idea to the acceptance of a new drug in the marketplace, and there are many challenges faced along the way to the patient. Collaborations and partnerships are an important part of this process. There are a variety of partnering opportunities, ranging from the discovery of novel technologies and drug targets to lead discovery, compound gifts, and external sourcing. These partnerships help increase confidence and improve decision making on issues of safety and efficacy preclinically, which can reduce attrition and expedite the provision of new quality drugs to patients more quickly and at lower costs. Collaborations involve addressing multiple issues that include infrastructure, safety, regulatory matters, intellectual property, technical and personnel considerations, source document capture and data analysis Issues, and legal and strategic alliances. A number of success factors are Identified as important for quality collaborations in the drug development process.
Gut Responses to Enteral Nutrition in Preterm Infants and Animals
Authors: Sangild Per T.
Published: January 2017

Preterm birth is associated with immature digestive function that may require the use of total parenteral nutrition and special oral feeding regimens. Little is known about the responses to oral food in the preterm neonate and how enteral nutrients affect the immature gastrointestinal tract (GIT). In vivo studies are difficult to perform in laboratory rodents because of their small body size and that of immature organs at birth, and this makes the large farm animals (e.g., pigs, cattle, sheep) more attractive models in this field. In these species, preterm delivery at 88%–95% gestation is associated clinical complications and degrees of GIT immaturity similar to those in infants born at 70%–90% gestation. Studies in both animals and infants indicate that the immature GIT responds to the first enteral food with rapid increases in gut mass and surface area, blood flow, motility, digestive capacity, and nutrient absorption. To a large extent, the enteral food responses are birth independent, and can be elicited also In utero, at least during late gestation. Nevertheless, preterm neonates show compromised GIT structure, function, and immunology, particularly when delivered by caesarean section and fed diets other than mother's milk. Formula-fed preterm infants are thus at increased risk of developing diseases such as necrotizing enterocolitis, unless special care is taken to avoid excessive nutrient fermentation and bacterial overgrowth. The extent to which results obtained in preterm animals (most notably the pig) can be used to reflect similar conditions in preterm infants is discussed.
Characterization of Ovarian Surface Epithelial Cells from the Hen: A Unique Model for Ovarian Cancer
Authors: Giles James R. , Olson Lisa M. , Johnson Patricia A.
Published: January 2017

To further develop the hen as a model of ovarian adenocarcinoma, we have studied normal and neoplastic ovaries as well as cultured cells from the ovarian surface epithelium (OSE). We characterized the OSE layer of the hen for specific histologic markers and evaluated these markers on tumor tissue. We also isolated and characterized the epithelial cells that are the likely source of the ovarian tumors of the hen. The surface epithelium of normal ovaries demonstrated positive staining for cytokeratin, proliferating cell nuclear antigen (PCNA), progesterone receptor (PR), and negative staining for vimentin. Ovarian tumors demonstrated positive cytokeratin, PCNA, PR, and weak vimentin staining in the gland-like areas. Epithelial cell cultures were obtained by an explant method utilizing small and large yellow follicles. These cells were positive for cytokeratin and negative for vimentin on Days 1 and 3. By Day 10, cytokeratin protein expression was less for some cells, and vimentin expression was weakly present in some cells. Expression of PCNA was observed at Days 1 and 3, but was rarely seen in cells cultured for 10 days. Expression of PR was observed on Day 10 after 24-hr estrogen treatment. Epithelial cells grew slowly in culture, and were susceptible to trypsin or other dissociation treatments.
L-carnitine contributes to enhancement of neurogenesis from mesenchymal stem cells through Wnt/β-catenin and PKA pathway
Authors: Fathi Ezzatollah , Farahzadi Raheleh , Charoudeh Hojjatollah Nozad
Published: January 2017

The identification of factors capable of enhancing neurogenesis has great potential for cellular therapies in neurodegenerative diseases. Multiple studies have shown the neuroprotective effects of L-carnitine (LC). This study determined whether neuronal differentiation of rat adipose tissue-derived mesenchymal stem cells (ADSCs) can be activated by LC. In this study, protein kinase A (PKA) and Wnt/β-catenin pathways were detected to show if this activation was due to these pathways. The expression of LC-induced neurogenesis markers in ADSCs was characterized using real-time PCR. ELISA was conducted to assess the expression of cyclic adenosine monophosphate (cAMP) and PKA. The expression of β-catenin, reduced dickkopf1 (DKK1), low-density lipoprotein receptor-related protein 5 (LRP5), Wnt1, and Wnt3a genes as Wnt/β-catenin signaling members were used to detect the Wnt/β-catenin pathway. It was observed that LC could promote neurogenesis in ADSCs as well as expression of some neurogenic markers. Moreover, LC causes to increase the cAMP levels and PKA activity. Treatment of ADSCs with H-89 (dihydrochloride hydrate) as PKA inhibitor significantly inhibited the promotion of neurogenic markers, indicating that the PKA signaling pathway could be involved in neurogenesis induction. Analyses of real-time PCR data showed that the mRNA expressions of β-catenin, DKK1, LRP5c-myc, Wnt1, and Wnt3a were increased in the presence of LC. Therefore, the present study showed that LC promotes ADSCs neurogenesis and the LC-induced neurogenic markers could be due to both the PKA and Wnt/β-catenin signaling pathway.

Impact statement

Neural tissue has long been believed as incapable of regeneration and the identification of cell types and factors capable of neuronal differentiation has generated intense interest. Mesenchymal stem cells (MSCs) are considered as potential targets for stem cell-based therapy. L-carnitin (LC) as an antioxidant may have neuroprotective effects in oxidative damage and possibly in neurodegenerative disorders. We have tried to evaluate the effect of LC as an antioxidant on the neurogenic differentiation of ADSCs in order to further elucidate the simultaneous effects on the capability of the neural regeneration. In this study, PKA and Wnt/β-catenin signaling pathways were detected to see if LC could also activate these pathways. The results of this study showed that 200 µM LC promoted ADSCs neurogenic differentiation, and that it was correlated with the PKA and Wnt/β-catenin signaling pathways.
God’s Case for Sex
Authors: Avishai Orit , Burke Kelsy
Published: January 2017

This article complicates a popular notion that conservative religions are incompatible with sexual expression and pleasure. Case studies from Orthodox Judaism and evangelical Protestant Christianity demonstrate a breadth of sexual expressions and negotiations of desire and sin that defy the association of conservative religions with sexual repression.
The Contemporary American University, In Seven Emails
Authors: Schuman Rebecca
Published: January 2017

Satirizing the debates and distractions bogging down the engaged academic.
Integrating Musculoskeletal Sonography Into Rehabilitation
Authors: Gray Julie McLaughlin , Frank Gelya , Roll Shawn C.
Published: January 2017

Musculoskeletal sonography is rapidly extending beyond radiology; however, best practices for successful integration into new practice contexts are unknown. This study explored non-physician experiences with the processes of training and integration of musculoskeletal sonography into rehabilitation. Qualitative data were captured through multiple sources, and iterative thematic analysis was used to describe two occupational therapists’ experiences. The dominant emerging theme was competency, in three domains: technical, procedural, and analytical. In addition, three practice considerations were illuminated: (a) understanding imaging within the dynamics of rehabilitation, (b) navigating nuances of interprofessional care, and (c) implications for post-professional training. Findings indicate that sonography training for rehabilitation providers requires multi-level competency development and consideration of practice complexities. These data lay a foundation on which to explore and develop best practices for incorporating sonographic imaging into the clinic as a means for engaging clients as active participants in the rehabilitation process to improve health and rehabilitation outcomes.
The Pink Elephant Paradox (or, Avoiding the Misattribution of Data)
Authors: Spiers Jude A.
Published: January 2017

The pink elephant paradox refers to the threat to inductive thinking caused by the difficulty of inadvertently proving the existence of a concept or phenomena just because it overtly or insidiously exists in one's thoughts, leading to misattribution, or miscategorization of data, and thus subverting inductive processes. As Morse and Mitcham discussed in Part I, this is reduced through inductive strategies, including processes of saturation, replication, and verification. In this article, I present a story of how the phenomenon of interest in nurse-patient interaction evolved and emerged through a number of qualitative projects. At each stage, concepts were identified, explored, and developed in order to more elucidate the central phenomenon. I will show how, while at times I could identify and avoid the pink elephant, at other times there were one or a herd lurking in the shadows or rampaging through my work. I think that discussing both the successes and pit falls is one way to acknowledge and address the fact that, although we accept the evolution in ideas and thought processes in qualitative research, we still may not be comfortable in articulating the far more complex and insidious threats to inductive processes.

Some schools of qualitative inquiry consider analysis of the literature a hindrance—in fact an invalidity—before commencing fieldwork. To the contrary, when a researcher is studying a concept rather than letting a concept emerge from a setting, it is essential to undertake a thorough theoretical and conceptual analysis of the literature (Morse, 2000; Morse et al, 1996). In my own program of research, the concept analysis was a study in, and of, itself, with the purpose of examining the maturity of concepts, and the explicit and implicit theoretical and research models. The literature constituted data that could be analyzed and formed the basis for a reconceptualization of the original concept by contrasting it with the theory derived from the fieldwork studies.
Searching for the Unknowable: A Process of Detection — Abductive Research Generated by Projective Techniques
Authors: Levin-Rozalis Miri
Published: January 2017

This article looks at the process of doing research ‘from scratch.’ The author began a project investigating children of Ethiopian origin living in Israel to see how ones who attended a kindergartern program years earlier differed from those who had not attended. However, the problem from the outset was that there may not be a difference to find. In this article, the author compares inductive, deductive, and abductive reasoning, and argues that abductive reasoning is the proper technique when nothing is known about the research at the outset.
Pieced Together: Collage as an Artist's Method for Interdisciplinary Research
Authors: Vaughan Kathleen
Published: January 2017

As a visual artist undertaking doctoral studies in education, the author required a research method that integrated her studio practice into her research process, giving equal weight to the visual and the linguistic. Her process of finding such a method is outlined in this article, which touches on arts-based research and practice-led research, and her ultimate approach of choice, collage. Collage, a versatile art form that accommodates multiple texts and visuals in a single work, has been proposed as a model for a “borderlands epistemology”: one that values multiple distinctive understandings and that deliberately incorporates nondominant modes of knowing, such as visual arts. As such, collage is particularly suited to a feminist, postmodern, postcolonial inquiry. This article offers a preliminary theorizing of collage as a method and is illustrated with images from the author's research/visual practice.
On Transcription and Other Aspects of the Craft of Qualitative Research
Authors: Farías Levy , Montero Maritza
Published: January 2017

El artículo procura contribuir a salvar la brecha entre el discurso oral y sus versiones escritas. Examina las formas de llevar a cabo la grabación y transcripción, no sólo para prevenir distorsiones importantes, sino también para destacar el carácter inevitablemente interpretativo de toda transcripción. Enfatiza especiamente los procedimientos artesanales por cuanto muchos estudiantes e investigadores en países no industrializados tienen poco acceso a la tecnología específica (tanto por razones económicas como de idioma), que aunque no elimina totalmente la intervención humana, ciertamente simplifica las tareas a ejecutar. Además describe una forma accesible de hacer tablas discursivas usando un conocido procesador de palabras y discute los grados y limitaciones de la edición o intervención del texto transcrito.
Talk/Reading/Voice: Re:search
Authors: Patterson Donna , Brogden Lace Marie
Published: January 2017

In this article, the authors embrace talk as space for emergence and possibilities. They flirt with the part reading plays (or might play) in conversations within the academy, recognizing such readings take multiple forms: individual, shared, in response, and in reaction (to name a few). To confront oneself with the not yet known is to witness what is forming or being called forth as its shaping emerges. Using co-constructed reading responses, the authors present examples from King's (2003) The Truth about Stories as illustrations of their work together, where work, like talk, is about pushing the edges of what can be known and, more particularly, about what can(not) be said. The authors maintain finding voice through reading, research, and self-study helps shape collaborative work within the academy. This reveal encourages the mapping of unmapped but taken for granted parts of academic life, an already querying of method.
Cross-National Field Research in Developing Countries
Authors: Karanasios Stan
Published: January 2017

Cross-national field research performed in developing countries presents researchers with a number of obstacles. Challenges include creating equivalent samples, countering biases, and managing linguistic and cultural issues. In this article the author reviews the conduct of a cross-national study focusing on small tourism operators and the adoption of information communication technologies. He presents the research process, the issues encountered and how they were addressed are discussed, and a number of lessons. This article adds to our understanding of cross-national field research in developing countries and presents a number of implications for social science researchers.
Redefining Qualitative Methods: Believability in the Fifth Moment
Authors: Lewis John
Published: January 2017

In this article the author addresses the history of reliability and validity in qualitative research as this method of inquiry has progressed through various paradigms. The importance of the concepts of reliability and validity in research findings is traced from the traditional era, where there was only a modest distinction between qualitative and quantitative researchers involving their definitions of research reliability and validity, through the current era, where some researchers question the need to be restricted in their research by attempting to control for or account for the reliability and validity of their research findings. The author rejects a strict need for reliability and validity as traditionally defined in quantitative research and outlines a less restrictive approach to ensuring reliability and validity in qualitative research.
Lost and Found in Translation: An Ecological Approach to Bilingual Research Methodology
Authors: Jagosh Justin , Boudreau J. Donald
Published: January 2017

Translation issues emerged from a qualitative study, conducted in French and English, that gathered patient perspectives on a newly implemented undergraduate medical curriculum entitled Physicianship: The Physician as Professional and Healer. French-speaking participants were interviewed using a translated interview guide, originally developed in English. A major finding that francophone participants contested the idea of the physician-healer in a manner not witnessed among the anglophone participants. Consultation with multilingual health professionals was undertaken to explore whether the contestation was the result of poor translation of the word healer. This process confirmed that no appropriate French equivalent could be found. With hindsight, the authors emphasize the importance of pretesting translated research instrumentation. An ecological perspective on language equivalency is also emphasized, in which emergent linguistic discrepancies are viewed as opportunities for learning about the culture-language relationship.