Distinct Serum Protein Pattern in Paranoid Schizophrena

Distinct Serum Protein Pattern in Paranoid Schizophrena A DISTINCT SERUM PROTEIN PATTERN IN PATIENTS WITH PARANOID SCHIZOPHRENIA[A1] N. A. Timofeyeva1,3, I. V. Alekseeva1,3, S. A. Ivanova2,4, G. G. Simutkin2, A. V. Semke2, I. S. Losenkov2, N. A. Bokhan2, O. S. Fedorova1,3, A. A. Chernonosov1,3* 1 Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk 630090, Russia 2 Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia 3 Novosibirsk State University, Novosibirsk, Russia       4 National Research Tomsk Polytechnic University, Tomsk, Russia ABSTRACT The proteomic approach, namely, a combination of 2D gel electrophoresis and matrix-assisted laser desorption ionisation time-of-flight mass spectrometry, is a powerful tool that allows researchers to identify proteins that are differentially expressed in disease states. Schizophrenia is a chronic mental illness, whose aetiology is still unclear; therefore, information about differences in serum protein patterns may improve the understanding of the pathophysiology of schizophrenia. The goal of this study was to use the proteomic approach to identify altered protein levels in the serum samples from patients with schizophrenia. For this study, blood was collected from 10 patients with paranoid schizophrenia and 10 healthy volunteers. We uncovered major changes in the expression of such proteins as apolipoproteins of classes A4 and C3, transthyretin (TTR), and serum amyloid A1. Furthermore, an increase in expression was found only for apolipoprotein A4, whereas the expression of apolipoprotein C3, TTR, and serum amyloid A1 was decreased. The observed differences in the expression of serum proteins (TTR and serum amyloid) are in good agreement with the results obtained by other research groups during analyses of cerebrospinal fluid or post-mortem brain tissues by other methods. Keywords: psychiatric disorder, schizophrenia, [A2]  proteomics, 2D electrophoresis, MALDI-TOF mass spectrometry, biomarker, serum. Introduction Although in recent years, great progress has been made in reducing mortality and in the treatment of common illnesses such as cancer and cardiovascular disease, the mortality caused by mental disorders remains unchanged [1]. Schizophrenia is a chronic mental illness, whose aetiology is still unclear. Schizophrenia is characterised by hallucinations, delusions (positive psychotic symptoms), affective problems [A3](negative psychotic symptoms), and cognitive dysfunction [2]. A number of hypotheses have been proposed about the pathogenesis of schizophrenia, for example, aberrations [A4]  in the pathways of transmission of neurotransmitters dopamine and serotonin [3, 4] or pathological changes in embryonic neurogenesis owing to variations in gene neuregulin-1 [5], as well as oxidative-stress-mediated cell damage due to lowered levels of antioxidant defence enzymes in patients with schizophrenia[A5] [6]. Such pathogenesis may be caused by a dysfunction of some enzymes (proteins) as well as changes of their quantity in the blood of these patients. At the same time, there is no information about differences in serum protein patterns that can be used for typing of psychopathologies among individuals at risk of developing psychiatric disorders [7]. Diagnosis and nosology rely on symptoms and accumulated clinical observations, and thus far, have been based mostly on interviews with patients and on patients subjective complaints [8]. Moreover, current medications still have substantial adverse effects and/or require weeks for therapeutic effects to manifest themselves; not all patients respond to current pharmacotherapy [9]. In sum, an insufficient understanding of psychiatric disorders at the molecular level and the lack of disease-specific changes in serum protein patterns prevent optimisation of diagnosis and treatment of such complex psychiatric disorders as schizophrenia  [A6]. The proteomic approach, namely, the combination of 2D gel electrophoresis and matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS), allows researchers to reliably identify proteins isolated from human bodily fluids [10, 11]. Our exploratory study [12] showed that 2D gel electrophoresis is suitable for isolation of proteins from blood of patients with mental disorders. Therefore  [A7], in the present work, clinical blood samples from patients with a diagnosis of schizophrenia were tested to identify quantitative differences in the proteomic profile of serum. Results and Discussion In this study, we examined blood serum of healthy people and patients with paranoid schizophrenia to search for quantitative and/or qualitative differences in proteins associated with this mental disorder. The use of 2D gel electrophoresis enables researchers to simultaneously isolate more than 300 protein spots on one gel containing 150  µg of protein for subsequent MALDI-TOF MS/MS analysis [10, 11]. We analysed differences in serum protein patterns by comparing the gels between the patients and healthy controls. The analysis [A8]  of protein patterns in serum was focused on those protein spots that differed in 2D gels between the patients and healthy controls. Such protein spots were analysed by means of the Gel-Pro Analyzer software and normalised to the sum of three proteins (a, b, Ñ ; for details, see Materials and Methods). These three proteins are isoforms of apolipoprotein L (ApoL) [18]. As a result, 15 protein spots were isolated and identified by peptide mass fin gerprinting and MS/MS analysis. The list of proteins identified in the NCBI database is shown in table [A9]1. Some proteins haptoglobin, transthyretin (TTR), and apolipoprotein C3 shown in table 1 are present in more than one spot on a gel and have different pI values. Perhaps this phenomenon is due to various post-translational modifications or partial processing. It was found that only the serum level of ApoA4 was increased (1.8-fold) as compared to the control group (figure 1a). Our findings support other [A10]  reports on altered protein levels in serum and cerebrospinal fluid in schizophrenia [19, 20].   Ã‚   The decrease in the serum concentration relative to the control group was observed for ApoC3 and for ApoC2 in patients with schizophrenia (figure 1b). This downregulation was on average from 1.8- to 3-fold for ApoC3, and smaller for ApoC2: only 1.25-fold. These proteins are synthesised in the liver and are components of very low-density lipoproteins (VLDLs). Apolipoprotein C2 activates extrahepatic lipoprotein lipase, whereas apolipoprotein C3 can inhibit lipoprotein lipase Fig. 1 Examples of proteins with differential expression in human serum are presented in the enlarged sections of the 2DE profile. a) Apo A4; b) Apo C3 and C2; c) serum amyloid A1; d) transthyretin (the protein is present in two spots because of post-translational modifications). Sch: schizophrenia. and activate LCAT [21, 22]. Previously, it was found that the expression of apolipoproteins is altered in schizophrenia, bipolar disorder, and other psychiatric disorders [23]. The authors found that low-density lipoproteins (LDLs) and VLDLs are the most prominent factors differentiating depressed patients from healthy controls, and that plasma unsaturated lipid concentrations are elevated in the depressed group. Thus, there is growing evidence that deregulated lipid homeostasis may play a common role in the pathophysiology of psychiatric disorders such as schizophrenia. Other proteins with a decreased concentration are serum amyloid A1 and TTR (figure 1c and 1d). Inflammatory amyloid A1 is among the so-called acute phase proteins, which have both direct and indirect bactericidal and/or bacteriostatic properties. According to the classical theory of inflammation, in the acute phase of inflammation, the serum concentration of amyloid A1 increases 100- to 1000-fold [24], whereas in our study, we observed a 2.3-fold decrease in the serum concentration of this protein in patients with schizophrenia. Perhaps this result  [A11] is due to decreased immunity in Table 1. The list of proteins from human serum analysed by 2DE and identified by MALDI-MS/MS after in-gel digestion with trypsin. Protein NCBI database no. Protein ID pI MW (kDa) Score (individuals/ significant) Fold Change (+/-)* Sch vs control 1 gi157831596 ÃŽÂ ±2-antitrypsin 5.37 44.3 48/45 -1.32  ± 0.2 2 gi338305 SP 40 5.74 36.7 17/10 -1.31  ± 0.09 3 gi3337390 Haptoglobin 6.14 38.2 35/29 +1.22  ± 0.13 4 gi114318993 Transthyretin (dimer) 5.16 20.2 120/84 -1.68  ± 0.25 5 gi11957960 Apolipoprotein A4 5.28 28.9 43/32 +1.84  ± 0.16 6 gi223976 Haptoglobin hp2ÃŽÂ ± 6.23 41.7 39/20 -1.38  ± 0.17 7 gi296653 Haptoglobin hp2ÃŽÂ ± 6.23 41.5 18/10 -1.42  ± 0.11 8 gi296653 Haptoglobin hp2ÃŽÂ ± 6.25 41.5 39/15 -1.56  ± 0.24 9 gi4507725 Transthyretin 5.52 15.9 75/52 -1.06  ± 0.13 10 gi4507725 Transthyretin 5.52 15.9 65/60 -1.45  ± 0.23 11 gi4557323 Apolipoprotein C3 5.23 10.8 112/70 -1.85  ± 0.21 12 gi4557323 Apolipoprotein C3 5.23 10.8 115/68 -3.28  ± 0.16 13 gi4557323 Apolipoprotein C2 5.42 11.2 104/78 -1.25  ± 0.08 14 gi40316910 Serum amyloid A1 6.28 13.5 134/90 -2.34  ± 0.09 15 gi19626079 Albumin fragment 6.20 22.4 56/40 -2.06  ± 0.32 The fold change is equal to SPi/SPcontrol, where i is the identification number of a spot. Symbols - and + mean a decrease and increase, respectively. Sch: schizophrenia. patients with psychiatric disorders or to the presence of comorbidities. In addition, [A12]  it is possible that a decrease in serum amyloid A1 concentration is related to downregulation of antioxidant-defence enzymes in patients with schizophrenia [6] because high-density lipoproteins (HDLs) inhibit oxidative modification of LDLs via the activity of their associated enzymes and apolipoproteins [25]. If HDLs become so-called dysfunctional HDLs because of accumulation of oxidants derived from an inflammatory reaction, such HDLs inhibit the HDL-associated antioxidant enzymes and reduce the ability of apolipoproteins A1 to promote ABCA-1-mediated cholesterol efflux [25]. In the literature, there are data on a strong positive relation between cholesterol levels and pathophysiological features of mood disorders. The link between mental health (brain) and cholesterol is believed to be based on hypothetical neuron-associated mechanisms. Cholesterol is an integral component of the plasma m embrane of neurons and is present in myelin. Furthermore, cholesterol performs crucial functions in the development, stability, and workings of the synapse [26]. Overall, aberrations in cholesterol in a psychiatric illness may substantially affect the mood via synaptic stability and lowered serotonergic activity. In the case of TTR, we observed a decrease in the serum concentration of its dimer and one of monomeric forms (protein 10 in Table 1) among the patients with schizophrenia (~1.7-fold and ~1.5-fold, respectively), whereas the serum level of another TTR monomeric form was found to be unchanged relative to the control group (protein 9 in Table 1). TTR is a liver-derived secretory protein and is the major serum carrier of thyroid hormones: thyroxine and tri-iodothyronine. TTR is also involved in the transport of retinol via an interaction with retinol-binding proteins. Several studies were conducted in an attempt to identify disease biomarkers that could advance the understanding of the pathogenesis of schizophrenia. In some of these studies, a link between TTR and schizophrenia was found [27, 28]. In ref. [28], it was estimated that 3% of TTR in ventricular cerebrospinal fluid [A13]  and 10% of TTR in lumbar cerebrospinal fluid are derived from blood. To assess the involvement of blood TTR in the changes observed in the cerebrospinal fluid of patients with schizophrenia, those authors also studied serum TTR levels in the same people (simultaneously with cerebrospinal fluid collection) by an ELISA. They observed a significant moderate decrease in TTR concentration in serum samples of patients with schizophrenia compared to co ntrols. Nevertheless, there was no association between cerebrospinal-fluid and serum TTR levels in the same individuals, indicating that the protein levels of TTR are regulated by different systems in serum and in cerebrospinal fluid. Conclusion In the present study, we identified differentially expressed proteins in the serum from patients with schizophrenia by proteomic analysis. We showed differential expression of such proteins as TTR, serum amyloid A1, and apolipoproteins of classes A4 and C3. Furthermore the increase in the expression was found only for apolipoprotein A4, whereas the expression of apolipoprotein C3, TTR, and serum amyloid A1 was decreased. Such alterations of the expression of these proteins may indicate problems with regulation, for example, in the synthesis. On the other hand, the altered protein expression may simply reflect the pathophysiological status of patients with schizophrenia, where these proteins could be candidates for biomarkers.   Nevertheless, to confirm the significance of the altered levels of these proteins in the pathogenesis [A14]  of schizophrenia, and to determine their suitability as biomarkers of schizophrenia, further research is needed. Competing interests. The authors declare that they have no conflicts of interest related to the contents of this article. Funding. This research was made possible in part by a grant from the Russian Science Foundation (14-15-00480, with the exception of the work corresponding to MALDI-TOF MS/MS analysis) and Federal Agency for Scientific Organizations (the part of work corresponding to MALDI-TOF MS/MS analysis). References Kessler RC, Demler O, Frank RG, Olfson M. 2005 Prevalence and treatment of mental disorders 1990 to 2003. N. Engl. J. Med. 352, 2515-2523. J. van Os, S. Kapur Schizophrenia. Lancet (Lond. Engl.), 374 (2009), pp. 635-645 H. Moore, A.R. West, A.A. Grace. The regulation of forebrain dopamine transmission: relevance to the pathophysiology and psychopathology of schizophrenia. Biol. Psychiatry, 46 (1999), pp. 40-55. M.A. Geyer, F.X. Vollenweider. Serotonin research: contributions to understanding psychoses. Trends Pharmacol. Sci., 29 (2008), pp. 445-453. E. Bramon, E. Dempster, S. Frangou, M. Shaikh, M. Walshe, F.M. Filbey, C. McDonald, P. Sham, D.A. Collier, R. Murray. Neuregulin-1 and the P300 waveform-a preliminary association study using a psychosis endophenotype. Schizophr. Res., 103 (2008), pp. 178-185 P.K. Ranjekar, A. Hinge, M.V. Hegde, M. Ghate, A. Kale, S. Sitasawad, U.V. Wagh, V.B. Debsikdar, S.P. Mahadik. Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Res., 121 (2003), pp. 109-122. Ivanova SA, Fedorenko OYu, Smirnova LP, Semke AV. 2013 Biomarker discovery and development of pharmacogenetic approaches to personalized therapy of patients with schizophrenia. Siberian vestnik of psychiatry and narcology. 12-16. Turck CW, Maccarrone G, Sayan-Ayata E, Jacob AM. 2005 The quest for brain disorder biomarkers. J. Med. Invest. 52, 231-235. Bystritsky A. 2006 Treatment-resistant anxiety disorders. Mol. Psychiatry. 11, 805-814. Davalieva K, Kostovska IM, Dwork AJ. 2016 Proteomic research in schizophrenia. Front. Cell. Neurosci. 16, (doi: 10.3389). Guest PC, Guest FL, Martins-de Souza D. 2016 Making sence of blood-based proteomics and metabolomics in psychiatric research. Int.J. of Neuropsychopharmacology. 719-728. Alekseeva IV, Timofeeva NA, Chernonosov AA, Ivanova SA, Bokhan NA, Fedorova OS. 2013 Use of two-dimensional electrophoresis for proteomic studies of serum from patients with mental disorders. Vestnik of Novosibirsk State University. Series: Biology, Clinical Medicine. 11, 56-60. PeÃ…Â ¡iĆ¡ I, Dihazi GH, Mà ¼ller GA, Jahn O, Hoffmann M, Eltoweissy M, Koziolek M, Dihazi H. 2011 Short-term increase of glucose concentration in PDS results in extensive removal and high glycation level of vital proteins during continuous ambulatory peritoneal dialysis. Nephrol. Dial. Transplant. 26, 2674-83. Giuliano S, Agresta AM, De Palma A, Viglio S, Mauri P, Fumagalli M, et al. 2014 Proteomic Analysis of Lymphoblastoid Cells from Nasu-Hakola Patients: A Step Forward in Our Understanding of This Neurodegenerative Disorder. PLoS ONE. 9(12): e110073. (doi:10.1371/journal.pone.0110073). Candiano G, Bruschi M, Musante L, Santucci L, Ghiggeri GM. 2004 Blue silver: a very sensitive colloidal Coomassie G-250 staining for proteome analysis. Electrophoresis. 25, 1327-1333. Brauner JM, Groemer TW, Stroebel A, Grosse-Holz S, Oberstein T, Wiltfang J, Kornhuber J, Maler JM. 2014 Spot quantification in two dimensional gel electrophoresis image analysis: comparison of different approaches and presentation of a novel compound fitting algorithm. BMC Bioinformatics. 15, 181-193. Perkins DN, Pappin DJ, Creasy DM, Cottrell JS. 1999 Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis. 20, 3551-3567. Lepedda AJ, Nieddu G, Zinellu E, De Muro P, Piredda F, Guarino A, Spirito R, Carta F, Turrini F, Formato M. 2013 Proteomic analysis of plasma-purified VLDL, LDL, and HDL fractions from atherosclerotic patients undergoing carotid endarterectomy: identification of serum amyloid A as a potential marker. Oxidative Medicine and Cellular Longevity. 2013, 1-11. Aphkhazava D, Nieves E, Callaway M, Olszewski W, Rotzschke O, Santambrogio L. 2013 Protein expression profiles of human lymph and plasma mapped by 2D-DIGE and 1D SDS-PAGE coupled with nanoLC-ESI-MS/MS bottom-up proteomics. J Proteomics. 78, 172-187. Wan CLa Y, Zhu H, Jiang L, Chen Y, Feng G, Li H, Sang H, Hao X, Zhang G, He L. 2007 Abnormal changes of plasma acute phase proteins in schizophrenia and the relation between schizophrenia and haptoglobin (Hp) gene.Amino Acids Amino Acids 1, 101-108. Eckel RH. 1989 Lipoprotein lipase: a multifunctional enzyme relevant to common metabolic diseases. N.Eng.J.Med. 320, 1060-1068. Wang HEckel RH. 2009 Lipoprotein lipase: from gene to obesity. Am. J. Physiol. Endocrinol. Metab. 297, 271-288. Zheng P, Gao HC, Li Q, Shao WH, Zhang ML, Cheng K, Yang de Y, Fan SH, Chen L, Fang L, Xie P. 2012 Plasma metabonomics as a novel diagnostic approach for major depressive disorder. J. Proteome Res. 11, 1741-8. doi: 10.1021/pr2010082. Baumann  H. 1994 The acute phase response. J. Gauldie: Immunologie Today. 2, 74-80. Vohnout, B., de Gaetano, G., Donati, M. B. and Iacoviello, L. (2011) The Relationship between Dyslipidemia and Inflammation, in Nutritional and Metabolic Bases of Cardiovascular Disease (eds M. Mancini, J. M. Ordovas, G. Riccardi, P. Rubba and P. Strazzullo), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781444318456.ch26 Chattopadhyay A, Paila YD. 2007 Lipid-protein interactions, regulation and dysfunction of brain cholesterol. Biochem. Biophys. Res. Commun. 16, 627-33. Wan C, Yang Y, Li H, La Y, Zhu H, Jiang L, Chen Y, Feng G, He L. 2006 Dysregulation of retinoid transporters expression in body fluids of schizophrenia patients. J. Proteome Res. 5, 3213-3216. Huang JT, Leweke FM, Oxley D, Wang L, Harris N, Koethe D, Gerth CW, Nolden BM, Gross S, Schreiber D, Reed B, Bahn S. 2006 Disease biomarkers in cerebrospinal fluid of patients with first-onset psychosis. PLoS Med. 3, (e428). [A1]Dear Author, Please dont forget to update the title in all supporting documents and correspondence. It often happens that after the language editing, coauthors make additions to the manuscript; also, some of the corrections are rejected. As a result, the manuscript that is submitted to the journal may contain 5-10 new errors. My advice is to send me the manuscript for a quick check on the day of the submission to the journal. I can use the automatic compare documents function of Word to find all new changes and to correct them quickly. I will also issue a certificate after this final check, and you can insert the sentence (optional) The English language was corrected and certified by shevchuk-editing.com. into Acknowledgments. [A2]Please do not include keywords that other researchers are unlikely to use when searching for articles. [A3]Affective disorders are depression and bipolar disorder. [A4]Please be careful with the words abnormal and abnormality when referring to a persons health status because they may be insulting to patients. [A5]Please note that this is a more polite form. [A6]Please avoid creating unusual abbreviations and single-word abbreviations because they make a text harder to read (well-known abbreviations such as DNA and official gene symbols are OK). The only valid reason for creating an abbreviation is the following: a long multiword expression (4 or more long words) that occurs more than 4 times in the text. Even in this case, it is better to avoid abbreviating. It is easy to write in abbreviations but it is difficult to decipher such a text. [A7]Please avoid creating long sentences because they are hard to read. [A8]Please note that the word study usually means the whole manuscript. [A9]The typical format is Table [A10]Please keep in mind that the word previous is redundant in this context because all published studies are previous. It is OK to say previous when you discuss your own earlier studies. [A11]Please dont use the words which or this as a substitute for the whole sentence or a statement. This usage is vague and confusing because some people will think that this or which refers to the last word, not the whole statement. Therefore, it is better to use a descriptive phrase instead. [A12]Its not a good idea to start a sentence with such words as and, but, also, or, so in a formal text. [A13]Please dont create abbreviations at the end of the article, after the full form was already used many times. [A14]= mechanism

Ancient Babylonia :: World History

Ancient Babylonia When studying Ancient Babylonia it is notably important to look at these factors: daily life, religion, people, society, government and economy so we can determine the development of the civilization and how it is similar to the way we live today. The Babylonian Empire is unique because their government was run by a law known as the Code of Hammurabi similarly are government is run by numerous laws. Their knowledge of science and astrology is intriguing due to the fact that they were the first civilization to form the basis of the sixteen month of thirty days calendar, their discovery of the calendar lend us to the calendars we have today. In addition to government, science and astrology their economy was very modern and played an immense part in their daily life. The way the Babylonians lived life is identical to the way we live our life today. In today's society we are governed and protected by laws, well we can say the same about Ancient Babylonia their society was governed and protected by the Code of Hammurabi(1750). The Code of Hammurabi main purposes were " to make justice visible in the land, to destroy the wicked person and the evil doer, so that the strong might not injure the weak". Our legal system is somewhat like this in terms of we sentence and enforce punishments on the criminals to protect other innocent citizens. Just like are prime minister, the Babylonian king Hammurabi wished to secure a uniform pattern of justice throughout his land, to certify that everyone was well aware of punishments and rules before breaking or committing them. The most well known term to describe this law is " an eye for an eye and a tooth for a tooth". This quote indicated that the punishment suited the crime. The Babylonian civilization was considerably keen on science, mathematics and astrology. They were apprehensive in the cause of medicine an example of this is their belief that sin was the cause of a patient's illness. Here is an old Babylonian proverb that says " an infection without a doctor is like hunger without food". What this is saying is they depended on doctors to suit their needs just as we depend on food to suit hunger. This describes perfectly what the Ancient Babylonian civilization was like, they depended on doctors and herbal medicine just as we do today.

“All the Years of Her Life” and “The Gentlemen of Rio en Medio” Essay

The thing about synonyms is that even though they though they might seem like they are the same thing, if put in a different context they can mean something completely different. It’s interesting how two characters with very similar traits, goals and morals can be so different when placed in different stories, like when you switch a word for its supposed â€Å"synonym†. Don Anselmo and Mrs. Higgins are two very similar people. Both are traditional, respected, a little on the old-fashioned side and good at being seen as proud and confident. But it’s their greatest linking factor, their love for their families and communities, which divides them. Don Anselmo is a proud, traditional and very well respected man who has kept up the tradition of planting a tree for every child in the village to the point where a â€Å"gnarled but beautiful† orchard had become a part of his property. And when he is confronted with the request to ask the children to refrain from playing in the orchard, he explains that it is not his choice nor his place, as â€Å"the trees do not belong to him†. To him, nothing is more important than respecting the honor of his family. And to him, every child in that village whether they’re related to him or not, is his family. On the other hand, Mrs. Higgins has too close of an association with her son to the point where she sees his problems as hers. She has a proud and confident facade that hides a spirit broken by reasons that are out of her control. She appears to blame herself for her son’s inability to keep a steady job and lead a good life. Like Don Anselmo she closely identifies herself with her family that in her case seems to have an ill effect on her lifestyle. â€Å"You’ve disgraced me again and again,† she told Albert as they left the pharmacy. She feels as if her son’s shenanigans are her fault and this causes her spirit to crumble. This isn’t the first time that her family has failed her, which in her eyes translates into failing as a mother. So as you can see, both characters have almost identical personality building blocks. On one hand, Don Anselmo has used his love and respect for family to create a bond between him and his village that lead to a tight knit  community. And on the other, Mrs. Higgins chose to use her tolerance and pride to create a poisonous relationship between her son’s lifestyle and her happiness.

King William II of England - William Rufus

King William II of England - William Rufus William II was also known as: Wlliam Rufus, the Red (in French, Guillaume Le Roux), though he may not have been known by this name during his lifetime. He was also identified by the nickname Longsword, given to him in childhood. William II was known for: His violent rule and his suspicious death. Williams forceful tactics earned him a reputation for cruelty and led to extreme dissatisfaction among the nobility. This has caused some scholars to theorize that he was assassinated.   Occupations: KingMilitary Leader Places of Residence and Influence: Britain: EnglandFrance Important Dates: Born: c. 1056Crowned King of England: Sept. 26, 1087Died: Aug. 2, 1100 About William II: A younger son of William the Conqueror, upon his fathers death William II inherited the crown of England while his elder brother Robert received Normandy. This caused immediate turbulence among those who thought it best that the Conquerors territory remain united under one rule. However, William was able to crush the rebellion of those seeking to put Robert in charge. Several years later, he had to put down a revolt by English noblemen. William also had trouble with the clergy, most especially Anselm, who he appointed Archbishop of Canterbury, and earned the enmity of Anselms supporters, some of whom later wrote chronicles casting the king in a bad light. In any case he was much more interested in military matters than clerical issues, and saw successes in Scotland, Wales and, eventually, Normandy.   In spite of the friction William seemed to spark throughout his reign, he managed to keep the political ties between England and Normandy strong. Unfortunately for him, he was killed in a hunting accident when he was only in his 40s. Although theories still circulate that he was murdered by his younger brother, who followed him to the throne as Henry I, there is no strong evidence to support this hypothesis, which on close inspection seems fairly unlikely. For more about the life and reign of William II, see his Concise Biography. More William II Resources: Concise Biography of William IIDynastic Table: Monarchs of England William II​ in Print The links below will take you to an online bookstore, where you can find more information about the book to help you get it from your local library. This is provided as a convenience to you; neither Melissa Snell nor About is responsible for any purchases you make through these links. William Rufus(English Monarchs)by Frank BarlowKing Rufus: The Life and Mysterious Death of William II of Englandby Emma MasonThe Killing of William Rufus: An Investigation in the New Forestby Duncan Grinnell-MilneThe Normans: The History of a Dynastyby David Crouch William II on the Web William IIBrief but informative bio from   The Columbia Electronic Encyclopedia at Infoplease. Whos Who Directories: Chronological Index Geographical Index Index by Profession, Achievement, or Role in Society The text of this document is copyright  ©2014 Melissa Snell. You may download or print this document for personal or school use, as long as the URL below is included. Permission is not granted to reproduce this document on another website. For publication permission, please visit Abouts Reprint Permissions page. The URL for this document is:http://historymedren.about.com/od/wwho/fl/William-II.htm

Change Your Life Forever by Spending 1 Hour a Day Doing These 5 Things

Change Your Life Forever by Spending 1 Hour a Day Doing These 5 Things Most people  only spend 8 hours per day at work. If you work 5  days a week, that’s 40 hours. Even if your job is super intense and you’re working 60-80 hour weeks, you still have hours and hours of time to yourself. Okay, you have to spend a lot of that sleeping- that’s important. But in the hours of leisure time left to you, there are things you could be doing to vastly improve your future. Rather than just blowing all those hours on happy hours and Netflix, why not try spending an hour a day doing these 5 things and see what happens? 1. Make your evenings matterDon’t just rely on your working hours to gain skills and knowledge and make your career magic happen. Try doing a little bit each day off the clock that will help you advance in your career, not just get your daily job tasks done. Take online classes, develop new skills, practice and master old ones. Keep pushing yourself to learn more and do more and you’ll be amazed at how much faste r you advance at work.2. Read moreIt almost doesn’t matter what you’re reading. Keeping the habit, taking in knowledge, considering other points of view- all of this makes you more interesting and interested in the world around you. One hour spent learning about a new topic makes you that much closer to being respected by your boss and peers as â€Å"in the know.† Plus, the benefits to your general knowledge and vocabulary will be palpable.3. Side projectsIf your company won’t give you the opportunity to take your new skills and interests for a test spin, try volunteering. Find a way to have practical expression of what you’re learning so it can really start to translate into workable results. If nothing else, these side hobbies and projects will help keep you feeling fulfilled.4. Build your networkEven if you just spend 10 minutes a day maintaining your contacts, reach out, participate in conversations on social media or LinkedIn, and pursue new o nes. You’ll start to see a major difference and that work will really pay off when you need to rely on your network to change jobs or take your career to the next level.5. Start nowDon’t start this next week- or after the holidays. Start tonight. Don’t put off what can become such an ingrained habit that you hardly realize it is a chore you’ve set yourself.If you can get to the point where you are doing these 5 things naturally? You’ll be well on your way to actualizing your success.

Current Event 2 Essay Example | Topics and Well Written Essays - 500 words

Current Event 2 - Essay Example The health risks increase as we move from lower-risk drinking to higher-risk drinking. Health problems caused as a result of drinking can vary from behavioral issues like depression, argumentation, and irritation to physical issues like sexual problems and liver damage. I consent with the author that the risks posed to health and relationships by the alcohol increase with the volume of alcohol that is consumed. There have to be different recommended levels for men and women considering their biological differences and their bodies’ reaction and response to alcohol. Although the article contains detailed information about what level of alcohol consumption makes an individual a lower-risk drinker, an increasing-risk drinker, or a higher-risk drinker, yet it does not say anything about the risks associated with switching from a lower-risk to a higher-risk or an increasing-risk drinker. I find this article very informative since now I know, what the recommended level of alcohol consumption for me is. However, since the author says that it cannot be said with utmost objectivity that one would only experience the said health risks with the consumption of a certain level of alcohol, it is better to consume no alcohol at all. I find that the safest and thus would not consume any alcohol at all. For the most part, the information contained in the article supports what we have read in the course. The author of the article says, â€Å"Theres no guaranteed safe level of drinking† (â€Å"The risks of†), and our textbook also declares alcohol as the most problematic substance that is consumed in our society (193). The article declares it a dangerous practice to be drunk even mildly before swimming or driving whereas the textbook gives alarming statistics of the number of students that lose their lives because of drinking every year by indulging in the same or similar practices. However, the textbook is

Effects of social media on juveniles and how that impact has changed Essay

Effects of social media on juveniles and how that impact has changed the way bullying is addressed - Essay Example Others are sentiments that are meant to bring someone down. This is the most modern way of bullying called cyber-bullying. Other social media that are equally to blame are television stations that air programs which bear characters with intimidating traits especially in a school setting where kids will use such people as their role models and may want to imitate them. These behaviors will then be taken to school and they will be portrayed as some violence and rude action at cafeteria, in the field and even in the hostels. Hence it has become a big problem (Roberts & Springer, 2007). To control bullying, all the people that mingle with juveniles must be involved .These include parents, teachers and the community as a whole. The three parties are supposed to take actions in these environments by fostering positive traits that build resilience and that promotes healthy development of successful learning. Teachers are supposed to punish or correct any form of bullying noted in school and the culprit reported to parents immediately before the bully becomes self-absorbed and like the attention. And become unbearable. This is the only long term solution to addressing bullying and other risky childhood behaviors (Hinduja & Patchin,