WordNet

yield to temptation or sin; "Adam and Eve fell"
the season when the leaves fall from the trees; "in the fall of 1973" (同)autumn
come as if by falling; "Night fell"; "Silence fell" (同)descend, settle
be born, used chiefly of lambs; "The lambs fell in the afternoon"
begin vigorously; "The prisoners fell to work right away"
go as if by falling; "Grief fell from our hearts"
occur at a specified time or place; "Christmas falls on a Monday this year"; "The accent falls on the first syllable"
pass suddenly and passively into a state of body or mind; "fall into a trap"; "She fell ill"; "They fell out of favor"; "Fall in love"; "fall asleep"; "fall prey to an imposter"; "fall into a strange way of thinking"; "she fell to pieces after she lost her work"
a lapse into sin; a loss of innocence or of chastity; "a fall from virtue"
a sudden decline in strength or number or importance; "the fall of the House of Hapsburg" (同)downfall
when a wrestlers shoulders are forced to the mat (同)pin
a movement downward; "the rise and fall of the tides"
come under, be classified or included; "fall into a category"; "This comes under a new heading" (同)come
lose an upright position suddenly; "The vase fell over and the water spilled onto the table"; "Her hair fell across her forehead" (同)fall down
fall to somebody by assignment or lot; "The task fell to me"; "It fell to me to notify the parents of the victims" (同)light
be inherited by; "The estate fell to my sister"; "The land returned to the family"; "The estate devolved to an heir that everybody had assumed to be dead" (同)return, pass, devolve
touch or seem as if touching visually or audibly; "Light fell on her face"; "The sun shone on the fields"; "The light struck the golden necklace"; "A strange sound struck my ears" (同)shine, strike
assume a disappointed or sad expression; "Her face fell when she heard that she would be laid off"; "his crest fell"
be captured; "The cities fell to the enemy"
be cast down; "his eyes fell"
be due; "payments fall on the 1st of the month"
come out; issue; "silly phrases fell from her mouth"
descend in free fall under the influence of gravity; "The branch fell from the tree"; "The unfortunate hiker fell into a crevasse"
die, as in battle or in a hunt; "Many soldiers fell at Verdun"; "Several deer have fallen to the same gun"; "The shooting victim fell dead"
drop oneself to a lower or less erect position; "She fell back in her chair"; "He fell to his knees"
lose office or power; "The government fell overnight"; "The Qing Dynasty fell with Sun Yat-sen"
lose ones chastity; "a fallen woman"
move in a specified direction; "The line of men fall forward"
slope downward; "The hills around here fall towards the ocean"
suffer defeat, failure, or ruin; "We must stand or fall"; "fall by the wayside"
to be given by assignment or distribution; "The most difficult task fell on the youngest member of the team"; "The onus fell on us"; "The pressure to succeed fell on the youngest student"
to be given by right or inheritance; "The estate fell to the oldest daughter"
undergo meiosis; "The cells reduce"
cook until very little liquid is left; "The cook reduced the sauce by boiling it for a long time" (同)boil_down, concentrate
be the essential element; "The proposal boils down to a compromise" (同)come_down, boil_down
take off weight (同)melt off, lose weight, slim, slenderize, thin, slim down
make smaller; "reduce an image" (同)scale_down
narrow or limit; "reduce the influx of foreigners" (同)tighten
make less complex; "reduce a problem to a single question"
cut down on; make a reduction in; "reduce your daily fat intake"; "The employer wants to cut back health benefits" (同)cut_down, cut_back, trim, trim down, trim back, cut, bring_down
bring to humbler or weaker state or condition; "He reduced the population to slavery"
destress and thus weaken a sound when pronouncing it
lessen and make more modest; "reduce ones standard of living"
lower in grade or rank or force somebody into an undignified situation; "She reduced her niece to a servant"
reposition (a broken bone after surgery) back to its normal site
simplify the form of a mathematical equation of expression by substituting one term for another
make smaller; "He decreased his staff" (同)lessen, minify
a process of becoming smaller or shorter (同)decrement
decrease in size, extent, or range; "The amount of homework decreased towards the end of the semester"; "The cabin pressure fell dramatically"; "her weight fell to under a hundred pounds"; "his voice fell to a whisper" (同)diminish, lessen, fall
the amount by which something decreases (同)decrement
the act of decreasing or reducing something (同)diminution, reduction, step-down
a change downward; "there was a decrease in his temperature as the fever subsided"; "there was a sharp drop-off in sales" (同)lessening, drop-off
the amount by which the cost of a business exceeds its revenue; "the company operated at a loss last year"; "the company operated in the red last year" (同)red ink, red
gradual decline in amount or activity; "weight loss"; "a serious loss of business"
something that is lost; "the car was a total loss"; "loss of livestock left the rancher bankrupt"
the disadvantage that results from losing something; "his loss of credibility led to his resignation"; "losing him is no great deprivation" (同)deprivation
the act of losing someone or something; "everyone expected him to win so his loss was a shock"
the experience of losing a loved one; "he sympathized on the loss of their grandfather"
inflect for number, gender, case, etc., "in many languages, speakers decline nouns, pronouns, and adjectives"
a condition inferior to an earlier condition; a gradual falling off from a better state (同)declination
change toward something smaller or lower (同)diminution
grow smaller; "Interest in the project waned" (同)go_down, wane
go down in value; "the stock market corrected"; "prices slumped" (同)slump, correct
go down; "The roof declines here"
any process in which electrons are added to an atom or ion (as by removing oxygen or adding hydrogen); always occurs accompanied by oxidation of the reducing agent (同)reducing
the act of reducing complexity (同)simplification
to a lower intensity; "he slowly phased down the light until the stage was completely black"
soft fine feathers (同)down feather
(American football) a complete play to advance the football; "you have four downs to gain ten yards"
fine soft dense hair (as the fine short hair of cattle or deer or the wool of sheep or the undercoat of certain dogs) (同)pile
(usually plural) a rolling treeless highland with little soil
understood perfectly; "had his algebra problems down" (同)down pat, mastered
extending or moving from a higher to a lower place; "the down staircase"; "the downward course of the stream" (同)downward
spatially or metaphorically from a higher to a lower level or position; "dont fall down"; "rode the lift up and skied down"; "prices plunged downward" (同)downwards, downward, downwardly
cause to come or go down; "The policeman downed the heavily armed suspect"; "The mugger knocked down the old lady after she refused to hand over her wallet" (同)knock down, cut_down, push down, pull down
shoot at and force to come down; "the enemy landed several of our aircraft" (同)shoot down, land
away from a more central or a more northerly place; "was sent down to work at the regional office"; "worked down on the farm"; "came down for the wedding"; "flew down to Florida"
becoming progressively lower; "the down trend in the real estate market"
being or moving lower in position or less in some value; "lay face down"; "the moon is down"; "our team is down by a run"; "down by a pawn"; "the stock market is down today"
being put out by a strikeout; "two down in the bottom of the ninth"
bring down or defeat (an opponent)
from an earlier time; "the story was passed down from father to son"
in an inactive or inoperative state; "the factory went down during the strike"; "the computer went down again"
not functioning (temporarily or permanently); "we cant work because the computer is down"
paid in cash at time of purchase; "put ten dollars down on the necklace"
shut; "the shades were down"
travel or traverse (a distance); "This car does 150 miles per hour"; "We did 6 miles on our hike every day"
the syllable naming the first (tonic) note of any major scale in solmization (同)doh, ut
proceed or get along; "How is she doing in her new job?"; "How are you making out in graduate school?"; "Hes come a long way" (同)fare, make_out, come, get along
create or design, often in a certain way; "Do my room in blue"; "I did this piece in wood to express my love for the forest" (同)make
carry on or function; "We could do with a little more help around here" (同)manage
get (something) done; "I did my job" (同)perform
bring into conformity with rules or principles or usage; impose regulations; "We cannot regulate the way people dress"; "This town likes to regulate" (同)regularize, regularise, order, govern
fix or adjust the time, amount, degree, or rate of; "regulate the temperature"; "modulate the pitch" (同)modulate
controlled or governed according to rule or principle or law; "well regulated industries"; "houses with regulated temperature"
English physician who first described Downs syndrome (1828-1896) (同)John L. H. Down

PrepTutorEJDIC

《しばしば副詞[句]を伴って》『落下する』,落ちる / 〈人・物が〉『倒れる』《+『down』(『over』)》 / 傷ついて倒れる,倒れて死ぬ / (…まで)垂れ下がる,〈道などが〉下降する《+『to』+『名』》 / 〈目・顔などが〉下を向く,うつむく,沈む / 〈暗やみ・静けさなどが〉(…に)たれ込める;〈災害・責任・病気・眠けなどが〉(…に)降りかかる《+『on』(『upon, over』)+『名』》 / 〈程度・数量・値段などが〉(…まで)『下がる』,減少する《+『to』+『名』》 / 誘惑に負ける,墜落する / (勢力・威信・人望などを)失う《+『from』(『in』)+『名』》 / 〈政権などが〉倒れる,〈要塞などが〉陥落する;(…の手に)落ちる《+『to』+『名』》 / 『なる』,陥る / 〈時・事が〉(…に)当たる,起こる,(しかるべき位置に)来る《+『on』(『upon』)+『名』》 / 〈光線・視線などが〉(…に)向けられる《+『on』(『upon』)+『名』 / (…に)分かれる《+『into』+『名』》 / 〈言葉などが〉(…から)漏れる《+『from』》 / 〈C〉(…から)『落ちること』,落下《+『from』+『名』》;(…への)落下《+『to』(『toward』)+『名』》 / 〈C〉(雨・雪などの)降った量《+『of』+『名』》 / 《複数形で》《固有名詞としては単数扱い》滝 / 〈C〉(…から…までの)落差《+『from』+『名』+『to』+『名』》 / 〈C〉倒れること,転倒 / 〈C〉(程度・数量・値段などの)下落,減少,衰退《+『in』+『名』》 / 《単数形で》(…の)陥落,崩壊《+『of』+『名』》 / 〈U〉堕落 / 〈C〉傾斜
『秋』(autumn)
(あるところまで)〈数量など〉‘を'『減らす』,小さくする;〈程度・地位など〉‘を'『下げる』《+『名』+『to』+『名』》 / 《しばしば受動態で》(ある状態・形に)…‘を'『する,』変える,至らせる《+『名』+『to』+『名』(do『ing』)》 / (単純な要素・部分に)…‘を'分解する,還元する《+『名』+『to』+『名』》 / …‘を'(…に)換算する,約分する《+『名』+『to』+『名』》 / 《話》〈人が〉減量する / 〈数量などが〉減る;〈程度・位などが〉下がる
…'を'『減らす』 / 『減る』,少なくなる / 〈U〉〈C〉(…の)『減少』,縮小《+『in』+『名』》 / 〈C〉(…の)減少量(額)《+『in』(『of』)+『名』》
〈U〉(…を)『失うこと』,紛失《+『of』+『名』》 / 〈C〉(…の)『損害』,損失;損失額《+『of』+『名』》 / 〈U〉〈C〉(…に)『負けること』,(…の)敗北;失敗《+『of』+『名』》 / 〈U〉(状態・程度の)『減少』,低下 / 《複数形で》(戦場における)(人の)損害,此傷者数
(穏やかに,礼儀正しく)…'を'『断る』,拒絶する,拒否する / 〈名詞・代名詞・形容詞〉'を'語形変化させる / 『断る』,辞退する / 《文》〈土地などが〉『下に傾く』;〈太陽・月が〉傾く / 《文》『衰える』,衰徴する / 『衰徴』,衰弱
〈U〉〈C〉(…を)『減らすこと』,減少,縮小,格下げ,(…の)割り引き《+『in』+『名』》 / 〈C〉減少(縮小)した量;割引額 / 〈C〉縮図,縮写 / 〈U〉換算約分
(高い所から)『下へ』,降りて,地面へ / (地理・地図上)南へ,下町へ;(風・流れなどが)『下(しも)手へ』;《英》(都会・大学から)地方へ,離れて / (価格・品質・温度などが)『下がって』,(数量・スピードなどが)少なく,減じて,(濃度が)薄く / (健康・風の勢いなどが)『衰えて』,気分が沈んで / (時代などが)下がって,…に至るまで / (身分・地位が)下がって / (紙面に)書き留めて,記録して / (頭金を)現金で,即金で / 最後まで,徹底的に / しっかりと,動けないように / (高い所から)…『を下がって』;…『に沿って』;…の向こうに / …の下流に / …以来 / 《名詞の前にのみ用いて》『下りの』,下への / 《名詞の前にのみ用いて》(列車・バスなどが)下りの / 《補語にのみ用いて》下に,下がって / 《補語にのみ用いて》弱まった,おさまった;落胆した,元気のない / 《補語にのみ用いて》(勝負で)負けて,すって / 《補語にのみ用いて》《おもに米話》(野球で)アウト / …‘を'打倒する,負かす,撃ち落とす / …‘を'飲み干す,飲み込む / 下り,下降 / 《複数形で》不運,逆境
(鳥の)綿毛,うぶ毛,下羽 / (植物・果実の表面の)柔らかい毛
なだらかな草原地,丘陵地帯(特にイングランド南部の小高い白亜質の草原地the Downsを言う)
《疑問文・否定文を作る》 / 《否定命令文を作る》 / 《助動詞とbe動詞のどちらも含まない文に用いて付加疑問を作る》 / 《強意語として》 / 《文》《助動詞とbe動詞のどちらも含まない文に用いて倒置文を作る》 / 《あいづちを打つ場合に》 / 《先行する動詞またはそれを含む述部の代用》 / 《so,nor,neitherで始まる簡略文で》 / …‘を'『する』,行う,果たす / 《通例have done,時にbe doneの形で》…‘を'『終える』,済ませる / …‘を'作る,作り出す / …‘を'『処理する』,整える,片付ける / 〈学課〉‘を'『勉強する』,専攻する / 〈利益・害など〉‘を'与える,もたらす / 〈人〉‘に'『役立つ』,用が足りる(serve) / …の速度で進む,距離を行く / …‘を'見物する / 〈劇〉‘を'上演する;…‘の'役を演じる / …の役目(仕事)をする / 《おもに英》…‘を'だます,かつぐ / 《話》…をへとへとにさせる / 『する』;活動する / 《通例have done,時にbe doneの形で》(…を)『終える』,済ます《+『with』+『名』》 / 〈事が〉『運ぶ』;〈人が〉暮らしていく,健康である / 〈物が〉(…に)『間に合う』,十分である;〈人が〉(…に)役に立つ,向く《+『for』+『名』》 / 《複数形で》すべきこと / 〈C〉《おもに英》大宴会,大パーティー / 〈C〉《英話》詐欺,ぺてん
ド(全音階の第1音)
(規則などで)…‘を'『規制する』,『統制する』 / 〈機械など〉‘を'『調整する』 / 〈量や率など〉‘を'ある限度内におさえる

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/12/24 10:03:22」(JST)

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[Wiki en表示]

Downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external variable. An increase of a cellular component is called upregulation.

An example of downregulation is the cellular decrease in the number of receptors to a molecule, such as a hormone or neurotransmitter, which reduces the cell's sensitivity to the molecule. This phenomenon is an example of a locally acting negative feedback mechanism.

An example of upregulation is the increased number of cytochrome P450 enzymes in liver cells when xenobiotic molecules such as dioxin are administered (resulting in greater degradation of these molecules).

Some receptor agonists may cause downregulation of their respective receptor(s), while most receptor antagonists may temporally upregulate their respective receptor(s). The disequilibrium caused by these changes often causes withdrawal when the long-term use of a medication or drug is discontinued. However, the use of certain receptor antagonists may also damage receptors faster than they upregulate (internalization of receptors due to antagonism).^{[citation needed]}

Upregulation and downregulation can also happen as a response to toxins or hormones. An example of upregulation in pregnancy is hormones that cause cells in the uterus to become more sensitive to oxytocin.

Receptor downregulation

Insulin receptor mechanism

The process of downregulation occurs when there are elevated levels of the hormone insulin in the blood. When insulin binds to its receptors on the surface of a cell, the hormone receptor complex undergoes endocytosis and is subsequently attacked by intracellular lysosomal enzymes. The internalization of the insulin molecules provides a pathway for degradation of the hormone as well as for regulation of the number of sites that are available for binding on the cell surface. At high plasma concentrations, the number of surface receptors for insulin is gradually reduced by the accelerated rate of receptor internalization and degradation brought about by increased hormonal binding. The rate of synthesis of new receptors within the endoplasmic reticulum and their insertion in the plasma membrane do not keep pace with their rate of destruction. Over time, this self-induced loss of target cell receptors for insulin reduces the target cell’s sensitivity to the elevated hormone concentration. The process of decreasing the number of receptor sites is virtually the same for all hormones; it varies only in the receptor hormone complex.

Cases

This process is illustrated by the insulin receptor sites on target cells in a person with type 2 diabetes. Due to the elevated levels of blood glucose in an overweight individual, the β-cells (islets of Langerhans) in the pancreas must release more insulin than normal to meet the demand and return the blood to homeostatic levels. The near-constant increase in blood insulin levels results from an effort to match the increase in blood glucose, which will cause receptor sites on the liver cells to downregulate and decrease the number of receptors for insulin, increasing the subject’s resistance by decreasing sensitivity to this hormone. There is also a hepatic decrease in sensitivity to insulin. This can be seen in the continuing gluconeogenesis in the liver even when blood glucose levels are elevated. This is the more common process of insulin resistance, which leads to adult-onset diabetes.

Another example can be seen in diabetes insipidus, in which the kidneys become insensitive to arginine vasopressin.

Reversal

The process of downregulation can be counteracted in the above example. A person with type 2 diabetes can increase their sensitivity to insulin through proper diet and regular exercise, resulting in weight loss; some individuals may even return to their pre-diabetic state by following such a regimen.

References

Sherwood, L. (2004). “Human Physiology From Cells to Systems, 5th Ed” (p. 680). Belmont, CA: Brooks/Cole-Thomson Learning

Wilmore, J., Costill, D. (2004). Physiology of Sport and Exercise, 3rd Ed (p. 164). Champaign, IL: Human Kinetics

External links

Down-Regulation at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. ダウン症：臨床的特徴および診断 down syndrome clinical features and diagnosis
2. Down syndrome: Overview of prenatal screening
3. ダウン症および18トリソミーに対するスクリーニングのための、妊娠初期におけるcombined testおよびintegrated test first trimester combined test and integrated tests for screening for down syndrome and trisomy 18
4. ダウン症の母体血清スクリーニングに関する臨床検査の問題 laboratory issues related to maternal serum screening for down syndrome
5. 胎児異数性に関連する超音波所見 sonographic findings associated with fetal aneuploidy

English Journal

Down-regulating ERK1/2 and SMAD2/3 phosphorylation by physical barrier of celecoxib-loaded electrospun fibrous membranes prevents tendon adhesions.

Jiang S1, Zhao X2, Chen S3, Pan G4, Song J5, He N6, Li F7, Cui W8, Fan C9.
Biomaterials.Biomaterials.2014 Dec;35(37):9920-9. doi: 10.1016/j.biomaterials.2014.08.028. Epub 2014 Sep 15.
Peritendinous adhesions, as a major problem in hand surgery, may be due to the proliferation of fibroblasts and excessive collagen synthesis, in which ERK1/2 and SMAD2/3 plays crucial roles. In this study, we hypothesized that the complication progression could be inhibited by down-regulating ERK1/2
PMID 25201739

Dual sensitive and temporally controlled camptothecin prodrug liposomes codelivery of siRNA for high efficiency tumor therapy.

Li Y1, Liu R2, Yang J3, Ma G3, Zhang Z4, Zhang X5.
Biomaterials.Biomaterials.2014 Dec;35(36):9731-45. doi: 10.1016/j.biomaterials.2014.08.022. Epub 2014 Sep 2.
The combination of chemotherapeutic drug camptothecin (CPT) and siPlk1 could prohibit cancer development with combined effects. To ensure the two drugs could be simultaneously delivered to tumor region with high loading content, and the modulator siPlk1 could be released in advance to down-regulate
PMID 25189519

Arbutin, an intracellular hydroxyl radical scavenger, protects radiation-induced apoptosis in human lymphoma U937 cells.

Wu LH1, Li P, Zhao QL, Piao JL, Jiao YF, Kadowaki M, Kondo T.
Apoptosis : an international journal on programmed cell death.Apoptosis.2014 Nov;19(11):1654-63. doi: 10.1007/s10495-014-1032-x.
Ionizing radiation (IR) can generate reactive oxygen species (ROS). Excessive ROS have the potential to damage cellular macromolecules including DNA, proteins, and lipids and eventually lead to cell death. In this study, we evaluated the potential of arbutin, a drug chosen from a series of tradition
PMID 25187044

Japanese Journal

Lactobacillus paracasei K71 Isolated from sakekasu (Sake Lees) Suppresses Serum IgE Levels in Ovalbumin-immunized Balb/c Mice

KUMAGAI Takehisa,IGUCHI Mariko,SHIGEYAMA Naoya,OKADA Sanae,JOH Toshio,HARA Takashi
Food Science and Technology Research 19(1), 127-132, 2013
… paracasei K71 may down-regulate IgE production via the induction of Th1 responses and suppression of Th2 responses in vivo. …
NAID 130003365225

Repressive processing of antihypertensive peptides, Val-Pro-Pro and Ile-Pro-Pro, in Lactobacillus helveticus fermented milk by added peptides(GENETICS, MOLECULAR BIOLOGY, AND GENE ENGINEERING)

Wakai Taketo,Yamaguchi Naoya,Hatanaka Misaki,Nakamura Yasunori,Yamamoto Naoyuki
Journal of bioscience and bioengineering 114(2), 133-137, 2012-08
… By DNA microarray analysis it was found that prtH2 corresponding to the cell wall-associated proteinase gene, most of the endopeptidase genes such as pepE, pep0l, pep02 and pep03, most of the oligopeptide transporter genes, such as dppA2, dppB, dppC, dppD and dppF, most likely involved in the processing of VPP and IPP were down-regulated. …
NAID 110009495417

Protein inhibitor of activated STAT, PIASy regulates α-smooth muscle actin expression by interacting with E12 in mesangial cells.

Torikoshi Kazuo,Abe Hideharu,Matsubara Takeshi,Hirano Takahiro,Ohshima Takayuki,Murakami Taichi,Araki Makoto,Mima Akira,Iehara Noriyuki,Fukatsu Atsushi,Kita Toru,Arai Hidenori,Doi Toshio
PloS one 7(7), 2012-07-19
… Recently, E-boxes and the class I basic helix-loop-helix proteins, such as E12 have been shown to regulateα-SMA expression. … These results suggest that TGF-β up-regulates PIASy expression in MCs to down-regulateα-SMA gene transcription by the interaction with E12. …
NAID 120004770223