Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of interleukin-1 beta gene in candidate human hematopoietic stem cells

Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect interleukin-1 beta (IL-1 beta) mRNA in candidate human hematopoietic stem cells. The cells, obtained from adult bone marrow (BM) or umbilical cord blood, had a CD34+ CD45RAlo CD71lo phenotype and were further fractionated into CD38+ and CD38- or Thy-1+ and Thy-1- subpopulations. The purity of these fractions was always more than 99%. IL-1 beta and CD34 mRNA were detected in pools of 30 BM-derived CD34+ CD45RAlo CD71lo cells. To further exclude any contribution by contaminating cells, individual cells were analyzed for CD34 and IL-1 beta mRNA. Positive results were obtained with 2 of 5 individual BM- derived CD34+ CD45RAlo CD71lo CD38+ cells isolated by micromanipulation after overnight culture in serum-free medium without any exogenous cytokines, and 1 of 10 individual CD34+ CD45RAlo CD71lo CD38- cells isolated immediately after sorting. Moreover, of 10 pools of three BM- derived CD34+ CD45RAlo CD71lo cells cultured overnight in the presence of a mixture of various cytokines (Steel factor, IL-3, IL-6, macrophage colony-stimulating factor [M-CSF], erythropoietin, and IL-3/granulocyte- macrophage colony-stimulating factor [GM-CSF] fusion protein), 5 were positive for IL-1 beta mRNA. This result was compatible with more than 20% (95% confidence limit 0.06–0.61) of the BM cells with the CD34+ CD45RAlo CD71lo phenotype expressing IL-1 beta mRNA. IL-1 beta expression was also consistently observed from day 0 to day 9 in liquid cultures of cord-blood-derived CD34+ CD45RAlo CD71lo Thy-1+ or Thy-1- cells. The cultures contained the same combination of cytokines and resulted in an expansion of cell numbers of up to 400-fold. GM-CSF mRNA was not detected in the equivalent of 75 cells at any day, even though it could be detected with high sensitivity in control stromal cells. Because IL-1 beta is a powerful and pleiotropic biomodulator of cytokines and adhesion molecules, our observations suggest that at least some primitive hematopoietic cells do not merely respond passively to signals from their environment, but may themselves regulate the paracrine production of cytokines from neighboring stromal cells. (ABSTRACT TRUNCATED AT 400 WORDS).
Reply

We thank Dr. Bhogal and Dr. Afford for their insightful comments on our article recently published in Liver Transplantation. We have been interested in dissecting interlocked gears of innate inflammatory cascades leading to the ischemia/reperfusion (IR) insult in liver transplant recipients. Our group was among the first to document that activation of sentinel Toll-like receptor 4 (TLR4) is required for the induction of IR-triggered hepatic inflammation, which ultimately leads to organ damage. By releasing proinflammatory mediators such as interleukin-1b, interleukin-6, and chemokine (C-X-C motif) ligand 10 downstream of TLR4 signaling, we have identified Kupffer cells as critical players in the mechanism of ischemia/reperfusion injury (IRI). Indeed, as Bhogal and Afford correctly pointed out, we have used mouse hepatoma cells in some of our in vitro experiments to demonstrate that targeting Janus kinase 2 decreases lipopolysaccharide (LPS)-mediated apoptosis. Ten years ago, Matsumura et al. documented that both mouse primary hepatocytes and hepatoma cells (the very same cell line that we employed in our study) respond to LPS stimulation by expressing functional TLR4. Moreover, the hepatoma cell line in our series (Hepat1-6, CRL-1830, American Type Culture Collection) is derived from the C57BL/6 mouse (the same strain that we used in our in vivo liver IRI model). Bhogal and Afford referred to published data showing in principle that hepatoma cells differ phenotypically and functionally from primary hepatocytes. However, the cited studies compare human hepatocytes and hepatoma cells with respect to drug (trovafloxacin) or food promutagen (dimethylnitrosamine and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) liver toxicity/metabolism. In fact, discovering that hepatoma cells do express higher mitochondria activity, which in turn may affect drug metabolism and/or toxicity study outcomes, is not unexpected. However, from an innate immunity mechanistic perspective, there is no doubt that LPS activates the mouse hepatoma cell line via the TLR4 pathway. Bhogal and Afford suggested that an in vitro model of warm IRI combining hypoxia and reoxygenation (HR) might be more suitable than a model of LPS stimulation during normoxia. Surprisingly, they referred to HR settings in the very same in vitro models using human cell lines that were dismissed earlier as unsuitable for our in vitro experiments. We do believe that both normoxia and HR in vitro mimic real-life liver IRI settings, but only to a certain extent. We reported for the first time the benefit of selective Janus kinase 2 targeting in the development of IRtriggered liver inflammation and hepatocellular damage. Our parallel in vitro experiments with mouse bone marrow macrophages and hepatoma cells support our in vivo findings. We are unaware of any published peer-reviewed data suggesting that putative metabolic differences between primary hepatocytes and hepatoma cell lines or between normoxia and hypoxia may affect outcomes of in vitro experiments designed to analyze TLR4-driven inflammation responses, the key mechanisms in the pathophysiology of liver IRI.
CaMKII‐dependent ryanodine receptor phosphorylation mediates sepsis‐induced cardiomyocyte apoptosis

Sepsis is associated with cardiac dysfunction, which is at least in part due to cardiomyocyte apoptosis. However, the underlying mechanisms are far from being understood. Using the colon ascendens stent peritonitis mouse model of sepsis (CASP), we examined the subcellular mechanisms that mediate sepsis‐induced apoptosis. Wild‐type (WT) CASP mice hearts showed an increase in apoptosis respect to WT‐Sham. CASP transgenic mice expressing a CaMKII inhibitory peptide (AC3‐I) were protected against sepsis‐induced apoptosis. Dantrolene, used to reduce ryanodine receptor (RyR) diastolic sarcoplasmic reticulum (SR) Ca2+ release, prevented apoptosis in WT‐CASP. To examine whether CaMKII‐dependent RyR2 phosphorylation mediates diastolic Ca2+ release and apoptosis in sepsis, we evaluated apoptosis in mutant mice hearts that have the CaMKII phosphorylation site of RyR2 (Serine 2814) mutated to Alanine (S2814A). S2814A CASP mice did not show increased apoptosis. Consistent with RyR2 phosphorylation‐dependent enhancement in diastolic SR Ca2+ release leading to mitochondrial Ca2+ overload, mitochondrial Ca2+ retention capacity was reduced in mitochondria isolated from WT‐CASP compared to Sham and this reduction was absent in mitochondria from CASP S2814A or dantrolene‐treated mice. We conclude that in sepsis, CaMKII‐dependent RyR2 phosphorylation results in diastolic Ca2+ release from SR which leads to mitochondrial Ca2+ overload and apoptosis.
SELF‐COMPATIBILITY AND ESTABLISHMENT AFTER ‘“LONG‐DISTANCE” DISPERSAL

lophaga and by the absence, also as primary infestants, of Anoplura. 8. The absence of Anoplura as primary infestants of South American land mammals seems to show that the sucking lice, as a group, originated at the earliest during the very late Mesozoic, if not at the beginning of the Tertiary. The reasons for this inference are: a) If sucking lice existed before the Pliocene in South America, they must have suffered complete extinction. This is hard to believe, especially because autochton rodents have proved very suitable hosts for cricetine-born Anoplura. As a matter of fact, the exchange of parasites has been much more intense in the cricetinehystricomorph direction than otherwise. b) If sucking lice existed in North America during the Paleocene, it is hard to believe they did not follow the heavy wave of immigration which entered South America at the time. c) Absence of sucking lice in North America at the Mesozoic-Tertiary boundary could only beexplained by either non-existence of the group or a very restricted distribution. This because the early Tertiary was a time of intensive faunal movements in Holarctica. d) If the Anoplura at that time had a restricted distribution, this should be due to very young age of the group, as they have proved very aggressive and succesful in colonizing empty ecological niches. 9. The possibility of detecting secondary infestations implies the possibility of evaluating evolutionary rates, as we are in a position to assign maximum lengths to the processes of divergence. Further knowledge of faunal movements inside South America will enhance the precision of such estimates. 10. We believe it would be rewarding to apply the methods outlined above to the fauna of other areas, especially the Oriental region and Africa. Otherwise, similar methods might be used for other couples of host-parasite groups, provided adequate taxonomic knowledge is available. Acknowledgments. The authors are indebted to a great many friends for help in preparing the paper of which this is an extract; these friends are listed in the article in Revista Brasileira de Entomologia. At the present time the authors wish to state their gratitude to the Editor of EVOLUTION for this opportunity of presenting their data to a much wider public than it would be possible otherwise.
STUDIES ON BIOLOGICAL FUNCTION AND PRODUCTION OF L-ORNITHINE

L-ornithine is a kind of middle metabolizing production, which is not make of protein. L-ornithine has various biological functions and is utilizatied in food industry and medical industry. Fermentation to produce ornithine is the best way of study in the world. The article introduces the biological functions and producation of ornithine in the world, including of breeding of mutant, questing for fermentation condition and industrializating production.
Reply

We applaud the discussion stimulated by our retrospective evaluation of therapeutic hypothermia (TH) in acute liver failure (ALF) published recently in Liver Transplantation. In this study of ALF patients from the US Acute Liver Failure Study Group (97 patients received TH; 1135 did not), TH was found to be generally safe (not associated with increased rates of bleeding or infection). In the acetaminophen (APAP) subgroup (TH group, 61; control group, 537), we explored a significant interaction term found in the multivariate model when we were examining the interaction between age and hypothermia in APAP ALF patients (see Table 1). We found that APAP ALF patients under the age of 25 years may potentially benefit from TH [odds ratio (OR) for age of 25 years, 2.735; 95% confidence interval (CI), 1.001-7.467]. In this subgroup, there were 101 patients (TH patients and controls); hence, we concluded that TH may potentially be associated with benefits in patients younger than 26 years with APAP ALF. One potential explanation for this is the lack of cortical atrophy in younger patients with a potentially increased risk of intracranial hypertension in hyperacute liver failure. Although it is true that our data show a statistically significant deleterious effect on patients older than 63 years old with APAP ALF (OR for age of 64 years, 0.167; 95% CI, 0.028-0.999), there were only 13 patients (TH patients and controls) who were older than 63 years. Because these patients made up only 2.2% of the overall APAP cohort and 1% of the overall cohort, we believe that it is not prudent to draw any significant conclusions on the basis of this subcohort. Although we attempted to account for severity of illness in our logistic regression, we cannot be certain that this small cohort of older APAP patients did not have other medical issues that were not taken into account in this model. This also highlights a flaw in simply plotting the ORs; not all data points are equally weighted. In summary, in the majority of ALF patients, TH did not have a helpful or harmful effect. This result is consistent with a recently completed European study. For younger APAP patients (n 5 101), there was a beneficial effect, and this has physiological plausibility. For the small subset of older patients (n 5 13), there may have been a harmful effect from hypothermia, but the pool of subjects was so small that it would be unwise to attribute causality to TH.
Reply

We thank Drs. Salehi and Shawcross for their comments on our publication “Reversal of acquired hepatocerebral degeneration with living donor liver transplantation. ” Our study includes a review of retrospective data of patients with acquired hepatocerebral degeneration (AHD) who were seen in 2013. Our case series gives us an insight that patients with AHD who are otherwise transplant candidates may have radiological and clinical reversal after liver transplant. Drs. Salehi and Shawcross quote a series published as correspondence in Hepatology. We would like to point out that our patients who underwent living donor liver transplantation were primarily liver transplant candidates and that neurological evaluation for Parkinsonism/movement disorders was performed during pretransplant workup and AHD was not a primary indication for liver transplant. Patients who are admitted with hepatic encephalopathy are routinely given rifaximin in our department because it became the standard of care, and our data have also been published. However, we believe that larger blinded studies over a longer period of time are needed before establishing that rifaximin used without liver transplantation may provide long-lasting benefits in AHD due to chronic liver disease. Ahmed Hassaan Qavi, M.B. B.S.
No Nonsense: The Protection of Wild-Type mRNAs From Nonsense-Mediated mRNA Decay in Saccharomyces cerevisiae

Nonsense-mediated mRNA decay is a translation-dependent surveillance mechanism responsible for rapidly degrading mRNAs with premature termination codons (PTCs). However, there is a significant portion of mRNAs that do not contain a PTC but are substrates for the NMD pathway. The underlying mechanisms of how the cellular machinery determines whether or not to degrade an mRNA via the NMD pathway are not well understood. Here we present the case of the Saccharomyces cerevisiae SSY5 mRNA, which is a wild-type mRNA containing multiple NMD-targeting signals, but is not degraded by the NMD pathway. We demonstrate that known mechanisms for the protection of mRNAs from NMD do not apply to SSY5 mRNA as the mRNA is translated and we do not find evidence of stop codon readthrough or translation reinitiation. Thus, the protection of the SSY5 mRNA from NMD is likely due to a novel mechanism that may provide further clues in unraveling the mystery of gene regulation and substrate recognition by NMD.
Reply:

1. Bondini S, Kallman J, Dan A, et al. Health-related quality of life in patients with chronic hepatitis B. Liver Int 2007; 27: 1119–25. 2. Ware JE, Sherbourne CD. The MOS 36-item Short-From Health Survey (SF-36): I. conceptual framework and item selection. Med Care 1992; 30: 473–81. 3. Brazier JE, Harper R, Jones NMB. Validating the SF-36 health survey questionnaire: new outcome measure for primary health. BMJ 1992; 305: 160–4. 4. Spiegel BM, Younossi ZM, Hays RD, Revicki D, Robbins S, Kanwal F. Impact of hepatitis C on health related quality of life: a systematic review and quantitative assessment. Hepatology 2005; 41: 790–800.
PTEN gene mutations in patients with macrocephaly and classic autism: A systematic review

Background: Autism Spectrum Disorder (ASD) is a neurological disorder characterized by massive damage in various fields of development. Impaired social interaction and communication skills, unusual behavior or interests, and repetitive activities are considerably disabling in these patients. There are several challenges in diagnosis of ASD patients such as co-existing epilepsy, difference in clinician attitudes and possibly multifactorial etiology of autistic behavior among children and adults. Research in recent years has emphasized a possible connection between mutations in PTEN and macrocephaly (head circumference > 97th centile). Methods: Articles in English Language were searched from international databases including Medline (PubMed), Google Scholar, Scopus, and CINHAL from January 1998 to January 2016. Results: The results showed that among 2940 patients with behavioral disorders, 2755 individuals had ASD, and 35 cases with macrocephaly had mutations in PTEN. About 77% of the articles (7/9) analyzed mutations in PTEN in patients with head circumference more than 2SD away from the mean, but did not check mutations in this gene in other ASD patients without macrocephaly. To the best of our knowledge, this study is the first systematic review on human PTEN mutations and classical autistic behavior. Conclusion: We conclude that the presence of macrocephaly may not be sufficient to examine the PTEN mutation in this group; however, surveying this gene in all cases of macrocephaly seems to be necessary.
Speciation and the evolution of mating preferences in threespine sticklebacks (Gasterosteus aculeatus)

My Ph.D. research has examined the evolution of mating preferences and their role in speciation. I have addressed these topics empirically, using sympatric species pairs of limnetic and benthic threespine sticklebacks, and theoretically, with multilocus population genetics. Sticklebacks are small fish that occur in lakes, streams and estuaries throughout British Columbia. Most lakes contain one type of stickleback, however, several lakes support two differentially adapted sympatric species: a large benthic form (benthic), and a smaller zooplanktivorous form (limnetic). Chapter 2 examines the role of species interactions in shaping male mating preferences. I determined that the mate preferences of the small species have shifted from preferring large females (the ancestral state) to preferring small females due either to selection against hybrids (reinforcement), or to egg predation by the larger benthic species. Chapter 3 explores the idea that sexual imprinting may facilitate assortative mating between benthic and limnetic sticklebacks. Sexual imprinting occurs when individuals imprint on the phenotype of their parents, and subsequently prefer mates that resemble their parents. The results suggested that sexual imprinting does not contribute to assortative mating between the sympatric species pairs, implying that genetics are more important than early learning for the formation of mate preferences. Chapter 4 focuses on differences in male breeding colour between benthics and limnetics. The results reveal that limnetic males have more intense red and blue coloration than benthic and solitary males. These differences in colour could be due to
Corrigendum

We wish to bring corrections to Künstner et al. (2010) to the attention of readers. Legends for Figures 2, 3, 7 and 8 were misplaced or not given correctly. These discrepancies do not influence any of the results or conclusions of our work. Corrected versions of the figure legends are shown below. The authors apologize for these errors and any inconvenience caused. Fig. 2 Proportion of contigs that align to different parts of non-coding RNA-genes and pseudogenes, as defined from alignment to the ENSEMBL zebra finch genome predictions. snoRNA, small nuclear RNA; miRNA, micro-RNA; rRNA, ribosomal RNA; miscRNA, miscellaneous RNA; pseudo, pseudogenes. Fig. 3 Proportion of contigs that align to different parts of zebra finch protein-coding genes, including coding
ISSN

—The use of treated wastewater is one of the ways to resolve a lack of water concerns. In this study, different responses of two kinds of grasses (C 3 : Lolium perenne L. and C 4 : Cynodon dactylon L . ) and four levels of wastewater (control, 25, 50, 75, and 100%) were evaluated at morphological and physiological levels. The concentration of Cd, Cr, Ni, As, and Cu elements significantly increased in leaf tissue under the toxic levels of wastewater (100%). The results showed that P n , T r , g s , WUEi, and chlorophyll significantly increased when grasses were under 50% wastewater treatment. Plants growth parameters including root, and shoot dry weights exhibited a significant increase under low concentration of wastewater while photosynthetic index and growth parameters showed a high reduction under high wastewater concentration. The results showed that by the handling of wastewater and the utilize of suitable concentrations, this unusual water source can be used for irrigation of grasses that need high water demands such as Lolium perenne and Cynodon dactylon .
Animals Study on Spirulina as an Adjuvant Blood Lipid Lowering and Immune Function Enhancing Agent

Objective The adjuvant blood lipid lowering and immune function enhancing activity of Spirulina in animal models were evaluated. Methods Rats and mice fed with high-fat diet were orally administered with Spirulina at doses of 0.4g/kg.bw,0.8g/kg.bw,2.4g/kg.bw for 30 days.Serum cholesterol(TC),triglyceride(TG),and high-density lipoprotein cholesterol(HDL-C) levels;and Cellular immunity,humoral immunity,clearance capacity of mononuclear-macrophages and NK cell activity were respectively monitored before and after the administration of Spirulina. Results As compared with the control high-fat-diet-fed rats,the 2.4g/kg.bw dose could significantly decrease serum cholesterol level(P0.05);0.8g/kg.bw,2.4g /kg.bw dose could significantly lower serum triglyceride level(P0.05), but Spirulina did not change the serum HDL-C level.As compared with the control mice,0.8g/kg.bw,2.4g/kg.bw dose could markedly enhance the carbon clearance capacity of mononuclear-macrophages,enhance the delayed type hypersensitivity and lymphocyte transformation capacity induced by ConA,and significantly increase antibody forming spleen cells.Spirulina showed no effect on NK cell activity. Conclusion Spirulina could assist blood lipid lowering and enhance immune function in rodents.
WHY DOES BONE MATRIX CONTAIN NON‐COLLAGENOUS PROTEINS? THE POSSIBLE ROLES OF OSTEOCALCIN, OSTEONECTIN, OSTEOPONTIN AND BONE SIALOPROTEIN IN BONE MINERALISATION AND RESORPTION

Four major non‐collagenous bone proteins were localised by single and double immuno‐histochemistry during de novo mineralisation and bone resorption. Both osteopontin and bone sialoprotein were localised ahead of the mineralisation front, suggesting that both proteins are necessary for the initiation of bone mineralisation. This supports previous suggestions that bone sialoprotein acts as a crystal nucleator. The role of osteopontin is less certain, but might be related to ensuring that only the right type of crystal is formed. Osteocalcin and osteonectin were not present in areas of first crystal formation, but were present in the fully mineralised matrix. Their role may be to control the size and speed of crystal formation.