MarketingWithoutAdvertisingby Michael Phillips & Salli Rasberryedited by Peri Pakroo3rd edition
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MarketingWithoutAdvertisingby Michael Phillips & Salli Rasberryedited by Peri Pakroo3rd edition
Keeping Up-to-DateTo keep its books up-to-date, Nolo issues new printings and new editions periodi-cally. New printings reflect minor legal changes and technical corrections. New edi-tions contain major legal changes, major text additions or major reorganizations. Tofind out if a later printing or edition of any Nolo book is available, call Nolo at 510-549-1976 or check our website at http://www.nolo.com.To stay current, follow the “Update” Metabolism without Oxygen Metabolism without Oxygen Bởi: OpenStaxCollege In aerobic respiration, the final electron acceptor is an oxygen molecule, O2 If aerobic respiration occurs, then ATP will be produced using the energy of high-energy electrons carried by NADH or FADH2 to the electron transport chain If aerobic respiration does not occur, NADH must be reoxidized to NAD+ for reuse as an electron carrier for the glycolytic pathway to continue How is this done? Some living systems use an organic molecule as the final electron acceptor Processes that use an organic molecule to regenerate NAD+ from NADH are collectively referred to as fermentation In contrast, some living systems use an inorganic molecule as a final electron acceptor Both methods are called anaerobic cellular respiration in which organisms convert energy for their use in the absence of oxygen Anaerobic Cellular Respiration Certain prokaryotes, including some species of bacteria and Archaea, use anaerobic respiration For example, the group of Archaea called methanogens reduces carbon dioxide to methane to oxidize NADH These microorganisms are found in soil and in the digestive tracts of ruminants, such as cows and sheep Similarly, sulfate-reducing bacteria and Archaea, most of which are anaerobic ( [link]), reduce sulfate to hydrogen sulfide to regenerate NAD+ from NADH 1/5 Metabolism without Oxygen The green color seen in these coastal waters is from an eruption of hydrogen sulfide-producing bacteria These anaerobic, sulfate-reducing bacteria release hydrogen sulfide gas as they decompose algae in the water (credit: modification of work by NASA/Jeff Schmaltz, MODIS Land Rapid Response Team at NASA GSFC, Visible Earth Catalog of NASA images) Link to Learning Visit this site to see anaerobic cellular respiration in action Lactic Acid Fermentation The fermentation method used by animals and certain bacteria, like those in yogurt, is lactic acid fermentation ( [link]) This type of fermentation is used routinely in mammalian red blood cells and in skeletal muscle that has an insufficient oxygen supply to allow aerobic respiration to continue (that is, in muscles used to the point of fatigue) In muscles, lactic acid accumulation must be removed by the blood circulation and the lactate brought to the liver for further metabolism The chemical reactions of lactic acid fermentation are the following: Pyruvic acid+NADH ↔ lactic acid + NAD + The enzyme used in this reaction is lactate dehydrogenase (LDH) The reaction can proceed in either direction, but the reaction from left to right is inhibited by acidic 2/5 Metabolism without Oxygen conditions Such lactic acid accumulation was once believed to cause muscle stiffness, fatigue, and soreness, although more recent research disputes this hypothesis Once the lactic acid has been removed from the muscle and circulated to the liver, it can be reconverted into pyruvic acid and further catabolized for energy Art Connection Lactic acid fermentation is common in muscle cells that have run out of oxygen Tremetol, a metabolic poison found in the white snake root plant, prevents the metabolism of lactate When cows eat this plant, it is concentrated in the milk they produce Humans who consume the milk become ill Symptoms of this disease, which include vomiting, abdominal pain, and tremors, become worse after exercise Why you think this is the case? Alcohol Fermentation Another familiar fermentation process is alcohol fermentation ( [link]) that produces ethanol, an alcohol The first chemical reaction of alcohol fermentation is the following (CO2 does not participate in the second reaction): Pyruvic acid → CO2 + acetaldehyde + NADH → ethanol + NAD + 3/5 Metabolism without Oxygen The first reaction is catalyzed by pyruvate decarboxylase, a cytoplasmic enzyme, with a coenzyme of thiamine pyrophosphate (TPP, derived from vitamin B1 and also called thiamine) A carboxyl group is removed from pyruvic acid, releasing carbon dioxide as a gas The loss of carbon dioxide reduces the size of the molecule by one carbon, making acetaldehyde The second reaction is catalyzed by alcohol dehydrogenase to oxidize NADH to NAD+ and reduce acetaldehyde to ethanol The fermentation of pyruvic acid by yeast produces the ethanol found in alcoholic beverages Ethanol tolerance of yeast is variable, ranging from about percent to 21 percent, depending on the yeast strain and environmental conditions Fermentation of grape juice into wine produces CO2 as a byproduct Fermentation tanks have valves so that the pressure inside the tanks created by the carbon dioxide produced can be released Other Types of Fermentation Other fermentation methods occur in bacteria Many prokaryotes are facultatively anaerobic This means that they can switch between aerobic respiration and fermentation, depending on the availability of oxygen Certain prokaryotes, like Clostridia, are obligate anaerobes Obligate anaerobes live and grow in the absence of molecular oxygen ...Khám phá khí Oxygen Mọi người đếu biết rằng lúc khởi thủy, không có oxygen trên trái đất. Khí quyển chỉ gồm các hợp chất nitrogen, hơi nước và khí carbonic được phóng thích ra từ các núi lửa, nhưng không có oxygen nguyên tố. Cách đây hai tỉ năm, sự ngưng tụ hơi nước và sự hình thành đại dương đã cho phép các vi sinh vật có thể tổng hợp diệp lục tố (rong, vi khuẩn), dùng khí carbonic và thải ra khí oxygen. Oxygen nhờ đó mà xuất hiện từ từ trong khí quyển, lúc đầu chỉ có 0,2%. Sau đó oxygen tạo thành tầng ozon, sẽ làm màn chắn bớt các tia tử ngoại (ultraviolet) tới mặt đất. Nhờ đó mà có được sự sống tập thể trên mặt đất. Sự phát triển mạnh mẽ của thực vật tạo lớp khí quyển càng ngày càng có nhiều oxygen Nhờ sự sản xuất oxygen mà trái đất ta đã qua một bước ngoặc mới trong lịch sử của nó. Trong một tì năm, cây dưới nước tiếp tục thải ra khí oxygen, và dần dần tụ lên bầu khí quyển
Khám phá khí oxygen: Nhà hóa học Thụy Điển Carl Wilhelm Scheele (1742-1786) nghiên cứu các chất khí vào những năm 1768-1770, đã quan sát một chất khí không mùi, khi đốt thì cho ra ngọn lửa sáng. Ông cho nó đặc điểm là "không khí của lửa". Tháng 4 năm 1774 Pierre Bayen thí nghiệm khi đốt oxyd thủy ngân (đá vôi thủy ngân, (chaux mercurielle ou mercure précipité per se), sẽ tỏa ra một chất khí và khối lượng bị mất. Ông hứng khí đó và ghi nhận rằng nó hơi đặc hơn không khí. Bayen cho rằng công bố quan sát này không ích lợi gì , ông muốn thực hiện những thí nghiệm tỉ mỉ hơn, cẩn thận hơn mà không xem xét chất khí thoát ra đó. Có phải ông cho rằng chất khí đó bình thường như mọi chất khác? Ngày 1 tháng 8 1774, Joseph Priestley làm thí nghiệm y hệt như Pierre Bayen tại khà ông gần Calne, Anh quốc. Ông thu được cùng chất khí trên và đặt tên là khí để đốt (air déphlogistiqué). Ông còn nhận thấy rằng chất khí này khi hít vô sẽ cảm thấy khoẻ và cây cối có thể làm tái sinh một phần chất khí mà chuột và ngọn lửa
thải ra. Từ các thí nghiệm trên, ông kết luận trên là không khí quanh ta gồm hai hợp chất, một chất làm hoạt động sự đốt và một cặn bã. Nói về chất khí này, ông viết: "cái làm cho tôi ngạc nhiên nhất là đèn cầy cháy bằng chất khí này có độ sáng rất mãnh liệt ." Ông cũng diễn tả một cách tỉ mỉ các thí nghiệm của ông và cho in ra các kết quả. Nhân dịp bữa ăn tối, khi Priestley được mời qua Pháp tháng 10 năm 1774 thì Lavoisier mới biết được sự khám phá ra chất khí đặc biệt mà ông gọi là "khí để hô hấp tốt hết sức" (air éminemment respirable) Lavoisier biết các công trình của Bayen nhưng cũng như Bayen, không để ý độ quan trọng của chất khí này. Sự gặp gỡ với Priestley là một phát hiện mới đối với Lavoisier: ông bị thu hút bởi các "khí" mới này và quyết định nghiên cứu các chất khí và những hiện tượng của sự đốt cháy. Bảy tháng sau, ông lập lại thí nghiệm của các nhà hóa học trên và thấy rằng "chất nhiên khí" đó là một nguyên tố mới, quan trọng hơn, là nguyên tố dùng để đốt. Ngoài ra ông thấy ngay sự gia tăng khối lượng của các kim loại khi bị nung khô (calcination). Năm 1775, ông thực hiện thí nghiệm đáng ghi nhớ trong 12 ngày và 12 đêm trên oxyd thủy ngân đỏ. Khí tỏa ra được nghiên cứu có đặc tình quan trọng: làm hoạt động Nanoparticles can induce changes in the intracellular
metabolism of lipids without compromising cellular
viability
Ewa Przybytkowski, Maik Behrendt, David Dubois and Dusica Maysinger
Department of Pharmacology and Therapeutics, McGill University, Montre
´
al, Canada
Introduction
Quantum dots (QDs) are colloidal semiconductor
nanoparticles (NPs) with unique luminescence charac-
teristics and wide biological and industrial applications
[1,2]. They could become attractive tools for imaging
in basic research and, eventually, in medicine [3]. How-
ever, some QDs can be harmful to cells, particularly if
Keywords
fat oxidation; hypoxia; lipid droplets;
nanoparticles; quantum dots
Correspondence
D. Maysinger, Department of Pharmacology
and Therapeutics, McGill University, 3655
Promenade Sir-William-Osler, Montre
´
al, QC,
Canada, H3G 1Y6
Fax: (514) 398 6690
Tel: (514) 398 1264
E-mail: dusica.maysinger@mcgill.ca
(Received 5 June 2009, revised 17 August
2009, accepted 24 August 2009)
doi:10.1111/j.1742-4658.2009.07324.x
There is growing concern about the safety of engineered nanoparticles,
which are produced for various industrial applications. Quantum dots are
colloidal semiconductor nanoparticles that have unique luminescence char-
acteristics and the potential to become attractive tools for medical imaging.
However, some of these particles can cause oxidative stress and induce cell
death. The objective of this study was to explore quantum dot-induced
metabolic changes, which could occur without any apparent cellular dam-
age. We provide evidence that both uncoated and ZnS-coated quantum
dots can induce the accumulation of lipids (increase in cytoplasmic lipid
droplet formation) in two cell culture models: glial cells in primary mouse
hypothalamic cultures and rat pheochromocytoma PC12 cells. Glial cells
treated with CdTe quantum dots accumulated newly synthesized lipids in a
phosphoinositide 3-kinase-dependent manner, which was consistent with
the growth factor-dependent accumulation of lipids in PC12 cells treated
with CdTe and CdSe ⁄ ZnS quantum dots. In PC12 cells, quantum dots, as
well as the hypoxia mimetic CoCl
2
, induced the up-regulation of hypoxia-
inducible transcription factor-1a and the down-regulation of the b-oxida-
tion of fatty acids, both of which could contribute to the accumulation of
lipids. On the basis of our results, we propose a model illustrating how
nanoparticles, such as quantum dots, could trigger the formation of intra-
cellular lipid droplets, and we suggest that metabolic measurements, such
as the determination of fat oxidation in tissues, which are known sites of
nanoparticle accumulation, could provide useful measures of nanoparticle
safety. Such assays would expand the current platform of tests for the
determination of the biocompatibility of nanomaterials.
Abbreviations
DIV 8, day (in vitro) 8; FAS, fatty acid synthase; FFA, free fatty acid; HIF-1a, hypoxia-inducible factor-1a; HIFs, hypoxia-inducible transcription
factors; LD, lipid droplet; NP, nanoparticle; PEG, polyethylene glycol; PI3K, phosphoinositide 3-kinase; PSN, penicillin ⁄ streptomycin ⁄
neomycin; QD, quantum dot; ROS, reactive oxygen species; SCD-1, stearoyl-coenzyme A desaturase-1; SREBP-1, sterol regulatory element
binding protein-1.
6204 FEBS Journal 276 (2009) 6204–6217 ª 2009 The Authors Journal compilation ª 2009 FEBS
their surface is not fully protected or if they degrade
within the biological environment. We have studied
the effects of QDs on living cells and have reported
their Primary research The effects of dopamine and epinephrine on hemodynamics and oxygen metabolism in hypoxic anesthetized piglets Po-Yin Cheung * and Keith J Barrington † * University of Alberta, Edmonton, Alberta, Canada † McGill University, Montreal, Quebec, Canada Correspondence: KJ Barrington, MBChB, FRCP(C), MRCP(UK), Room C7.68, Royal Victoria Hospital, 687 Pine Ave W, Montreal, Quebec, Canada H3A 1A1. Tel: 514 842 1231 (ext 4876); fax: 514 843 1741; e-mail: kbarri@po-box.mcgill.ca CI = cardiac index; EO 2 = oxygen extraction; HAFI = hepatic arterial flow index; hepatic DO 2 = hepatic oxygen delivery; hepatic DO 2 ratio = ratio of hepatic arterial oxygen delivery to total hepatic oxygen delivery; MVRI = mesenteric vascular resistance index; PAP = mean pulmonary arterial pres- sure; PVFI = portal venous flow index; PVRI = pulmonary vascular resistance index; S a O 2 = arterial saturation; SAP = mean systemic arterial pres- sure; S p O 2 = portal venous saturation; S v O 2 = mixed venous saturation; SVRI = systemic vascular resistance index; VO 2 = oxygen consumption; THFI = total hepatic flow index. Available online http://ccforum.com/content/5/3/158 Abstract Background: The most appropriate inotropic agent for use in the newborn is uncertain. Dopamine and epinephrine are commonly used, but have unknown effects during hypoxia and pulmonary hypertension; the effects on the splanchnic circulation, in particular, are unclear. Methods: The effects on the systemic, pulmonary, hepatic, and mesenteric circulations of infusions of dopamine and epinephrine (adrenaline) were compared in 17 newborn piglets. Three groups [control (n = 5), dopamine (n = 6) and epinephrine (n = 6)] of fentanyl anesthetized newborn piglets were instrumented to measure cardiac index (CI), hepatic arterial and portal venous blood flow, mean systemic arterial pressure (SAP), mean pulmonary arterial pressure (PAP), and arterial, portal and mixed venous oxygen saturations. Systemic, pulmonary, and mesenteric vascular resistance indices [systemic vascular resistance index (SVRI), pulmonary vascular resistance index (PVRI), mesenteric vascular resistance index (MVRI)], and systemic and splanchnic oxygen extraction and consumption were calculated. Alveolar hypoxia was induced, with arterial oxygen saturation being maintained at 55–65%. After 1 h of stabilization during hypoxia, each animal received either dopamine or epinephrine; randomly administered doses of 2, 10, and 32 µgkg –1 min –1 and 0.2, 1.0, and 3.2 µgkg –1 min –1 respectively were infused for 1 h at each dose. Results were compared with the 1 h hypoxia values by two-way analysis of variance. Results: Epinephrine increased CI at all doses, with no significant effects on SAP and SVRI. Although epinephrine increased PAP at 3.2 µg kg –1 min –1 , it had no effect on PVRI. Dopamine had no effect on CI, SAP, and SVRI, but increased PAP at all doses and PVRI at 32 µgkg –1 min –1 . The SAP/PAP ratio was decreased with 32 µgkg –1 min –1 dopamine, whereas epinephrine did not affect the ratio. In the mesenteric circulation, dopamine at 32 µgkg –1 min –1 increased portal venous flow and total hepatic blood flow and oxygen delivery, and decreased MVRI; epinephrine had no effect on these variables. Epinephrine increased hepatic arterial flow at 0.2 µgkg –1 min –1 ; dopamine had no effect on hepatic arterial flow at any dose. Despite these hemodynamic changes, there were no differences in systemic or splanchnic oxygen extraction or consumption at any dose of dopamine or epinephrine. Conclusions: Epinephrine is more effective than dopamine at increasing cardiac output during hypoxia in this model. Although epinephrine preserves the SAP/PAP ratio, dopamine shows preferential pulmonary vasoconstriction, which might be detrimental if it also occurs during the management of infants with persistent fetal circulation. Dopamine, but not epinephrine, increases portal flow and total hepatic flow during hypoxia. Keywords: Graduate School ETD Form 9 (Revised 12/07) PURDUE UNIVERSITY GRADUATE SCHOOL Thesis/Dissertation Acceptance This is to certify that the thesis/dissertation prepared By Entitled For the degree of Is approved by the final examining committee: Chair To the best of my knowledge and as understood by the student in the Research Integrity and Copyright Disclaimer (Graduate School Form 20), this thesis/dissertation adheres to the provisions of Purdue University’s “Policy on Integrity in Research” and the use of copyrighted material. Approved by Major Professor(s): ____________________________________ ____________________________________ Approved by: Head of the Graduate Program Date America Bethanne Newnum Bone Metabolism: The Role of STAT3 and Reactive Oxygen Species Master of Science Jiliang Li James Marrs Julie Ji Jiliang Li Simon Atkinson 06/25/2012 Graduate School Form 20 (Revised 9/10) PURDUE UNIVERSITY GRADUATE SCHOOL Research Integrity and Copyright Disclaimer Title of Thesis/Dissertation: For the degree of Choose your degree I certify that in the preparation of this thesis, I have observed the provisions of Purdue University Executive Memorandum No. C-22, September 6, 1991, Policy on Integrity in Research.* Further, I certify that this work is free of plagiarism and all materials appearing in this thesis/dissertation have been properly quoted and attributed. I certify that all copyrighted material incorporated into this thesis/dissertation is in compliance with the United States’ copyright law and that I have received written permission from the copyright owners for my use of their work, which is beyond the scope of the law. I agree to indemnify and save harmless Purdue University from any and all claims that may be asserted or that may arise from any copyright violation. ______________________________________ Printed Name and Signature of Candidate ______________________________________ Date (month/day/year) *Located at http://www.purdue.edu/policies/pages/teach_res_outreach/c_22.html Bone Metabolism: The Role of STAT3 and Reactive Oxygen Species Master of Science America Bethanne Newnum 06/25/2012 BONE METABOLISM: THE ROLE OF STAT3 AND REACTIVE OXYGEN SPECIES A Thesis Submitted to the Faculty of Purdue University by America Bethanne Newnum In Partial Fulfillment of the Requirements for the Degree of Master of Science August 2012 Purdue University Indianapolis, Indiana ii ii This thesis is dedicated to Daria Rancid, my best friend, daughter, and furry life partner for 15 adorable years. Your refusal to give up on life after being diagnosed with leukemia has given me more strength than your kitty brain will ever realize. I also want to dedicate this work to Sahib Ali, who not only never failed to support me during my graduate school career, but made sure that I didn’t starve to death or go completely insane after I broke my leg halfway through my MS program. I also can’t forget Sunday Sprinkles and Willow Pillow, who staged episodes of “WWE Kitty Smackdown” in our living room to distract and amuse me. Last but not least, my four parents, Ron Newnum, Linda Holycross, Patty Kelly, and Darrell Holycross, for their encouragement during this process. iii iii ACKNOWLEDGEMENTS I would like to thank Dr. Li for his patience and understanding during my unconventional graduate career, and also my committee members Dr. James Marrs and Dr. Julie Ji. I would like to thank Kevin Zhou for his invaluable help in the lab and his friendship outside the lab, and Dr. Robert Yost for the opportunity to serve as a TA for K103 lab for four wonderful semesters. Last but not least, I would like to thank Dr. Keith Condon for allowing our lab to use his facilities to process our bone samples. iv iv TABLE OF CONTENTS Page LIST OF FIGURES i LIST OF ABBREVIATIONS viii ABSTRACT x CHAPTER 1.INTRODUCTION 1 1.1 Bone ... the sixth step in glycolysis Without these pathways, that step would not occur and no ATP would be harvested from the breakdown of glucose 4/5 Metabolism without Oxygen Section Summary If NADH... proceed in either direction, but the reaction from left to right is inhibited by acidic 2/5 Metabolism without Oxygen conditions Such lactic acid accumulation was once believed to cause muscle stiffness,... in the second reaction): Pyruvic acid → CO2 + acetaldehyde + NADH → ethanol + NAD + 3/5 Metabolism without Oxygen The first reaction is catalyzed by pyruvate decarboxylase, a cytoplasmic enzyme,