早稲田教育学部 傾向対策解答解説 2019問題4
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早稲田教育学部 2019問題4
【大問４ 読解問題】
次の英文を読み、設問１から１０に答えよ。答えはa~dから１つずつ選べ。
(１)Even the toughest prisoners fear solitary confinement. There is a growing awareness across the globe that we are facing an epidemic of loneliness. Prolonged social isolation and loneliness can lead to many profound physiological and neuropsychiatric conditions, including depression and heart disease, and to increased mortality rates. But the biological mechanisms underlying the effects of social isolation are poorly understood. Writing in Cell, Zelikowsky et al. reveal a signalling mechanism that acts in several brain regions in mice to drive some of the harmful effects of the stress caused by chronic social isolation.
The authors examined the effects of two weeks of social isolation on the brains and behaviour of male mice (equivalent to more than a year in these conditions for humans). First, the researchers used an array of behavioural tests to compare mice kept in isolation with control mice that had been housed in groups. These assays revealed widespread effects. Compared to control animals, isolated mice showed enhanced aggression and hypersensitivity to diverse stressful stimuli. For example, the socially isolated mice responded more aggressively to an unfamiliar mouse placed in their cage. In another assay, the researchers presented mice with a dark circle that loomed overhead, simulating an approaching predator. Control animals froze in response to (２)the threat, but moved normally after the stressful stimulus was removed, whereas isolated mice remained frozen long after the apparent threat was removed.
Next, Zelikowsky et al. investigated the brain mechanisms underlying this behaviour. In a previous study of fruit flies, the same group had identified the gene Tac as essential for the regulation of aggression induced by social isolation. Rodents have two versions of Tac, which are expressed in various brain regions, including regions associated with social behaviour, anxiety and emotions. Using several independent methods, Zelikowsky and colleagues now found a massive increase in the (３)expression of Tac2 throughout the brain following social isolation.
The gene Tac2 encodes a protein called neurokinin B (NkB), which binds specifically to the receptor Nk3R. The researchers performed a series of experiments to alter NkB signalling in the brain. First, they systemically inhibited NkB signalling in isolated male mice using a drug called osanetant, which inhibits the activity of Nk3R. Administration of osanetant, either throughout the social-isolation period or 20 minutes before behavioural testing, substantially reduced the effects of social isolation on behaviour. Next, the authors genetically upregulated Tac2 expression and simultaneously activated Tac2-expressing neurons in group-housed animals, using specially designed viruses that were injected intravenously but could cross the blood-brain barrier to reach the brain. They found that (４)this genetic manipulation led to group-housed mice (５)behaving in a similar way to those that had been isolated.
This work opens a gateway to much future research. First and foremost, it will be interesting to determine whether (６)TAC3, the human equivalent of Tac2, is involved in mediating the effects of loneliness and social isolation in people. To our knowledge, TAC3 has not yet been directly associated with sociality or social behaviour of any kind in humans. However, it is expressed in the human brain and has shown abnormal gene-expression levels in children with autism-spectrum disorder, which profoundly affects social interaction. The systemic manipulations presented in Zelikowsky and colleagues' paper could be rapidly applied to humans, because osanetant and other NkB inhibitors have already been tested in clinical trials. These drugs could potentially treat anti-social disorders induced by isolation, as well as mood and anxiety disorders.
Finally, one has to wonder: to what extent can we rely on a mouse model of social isolation to truly examine the underlying mechanisms of human loneliness? After all, loneliness and mental isolation are subjective, and a person might feel alone even when surrounded by other people. The traits exhibited by mice under prolonged social isolation greatly resemble those found in humans experiencing solitary confinement, so these animals do provide a good model for studying, (７)this process. What we currently lack are relevant animal models for other forms of human loneliness, such as social withdrawal or antisocial personality disorder. Expanding our research toolbox — for example, by studying various species, including non-social and community-living animals, as well as humans — might bring us closer to understanding the biology of human loneliness.
Noga Zilkha. A molecular signature for social isolation identified in the brain.
1 What is meant by underline (1)?
a. Prisoners must be confined alone.
b. No one is tough enough to endure complete isolation.
c. Everyone fears tough prisoners.
d. Tough prisoners must endure solitary confinement.
2 Which of the following is NOT an appropriate substitute for underline (2)?
a. the researcher
b. a dark circle that loomed overhead
c. the stressful stimulus
d. an approaching predator
3 Which of the words below is closest in meaning to underline (3)?
a. application
b. appearance
c. departure
d. description
4 What is meant by underline (4)?
a. intravenous injection of a drug called osanetant
b. upregulation of Tac2 expression
c. activation of Tac2-expressing neurons
d. upregulation of Tac2 expression and activation of Tac2-expressing neurons
5 What is meant by underline (5)?
a. behaving amicably to an approaching predator
b. behaving normally to diverse stressful stimuli
c. behaving aggressively to an unfamiliar animal
d. behaving abnormally to a familiar animal
6 Which of the following statements about underline (6) is true?
a. TAC3 has been found to mediate the effects of loneliness and social interaction in male mice.
b. TAC3 has not yet been systemically manipulated by Zelikowsky and colleagues.
c. TAC3 is directly linked to sociality or social behavior in humans.
d. TAC3 has already been manipulated in clinical trials using NkB inhibitors like osanetant.
7 What is meant by underline (7)?
a. mice undergoing prolonged social isolation
b. humans experiencing solitary confinement
c. a person not feeling alone when surrounded by other people
d. scientists expanding their research paradigm
8 Which of the following statements correctly describes the findings by Zelikowsky et al.?
a. TAC3 is the human equivalent of Tac2 and mediates the effects of loneliness and social isolation in people.
b. There is a genetic basis in humans for some of the mental effects caused by social isolation.
c. Feelings such as loneliness and isolation are basically the same for animals and humans.
d. How social isolation triggers harmful mental effects in mice can be described in neuro-scientific terms.
9 Which of the following statements matches the content of the article?
a. A mouse model of social isolation is readily applicable to humans.
b. The biological mechanisms underlying the effects of social isolation are well researched and understood.
c. There are drugs which could potentially treat anti-social disorders induced by isolation, as well as mood and anxiety disorders.
d. It is proved by experiments on mice that lengthy social isolation and loneliness can cause non social behaviours, such as withdrawal.
１０ What is the main theme of the article?
a. understanding loneliness and social isolation in non-human communities
b. understanding social withdrawal in animals
c. understanding the consequences of genetic manipulation
d. understanding the biological mechanisms of the effects of social isolation in animals and humans Tars
早稲田教育学部 2019問題4 解答
【大問４ 読解問題 解答】
1 b
2 a
3 b
4 d
5 c
6 b
7 b
8 d
9 c
10 d
早稲田教育学部 2019問題4 解説
【大問４ 読解問題 解説】
説明文。長文を読み進めながら適語補充し、まとめて内容理解が問われます。大問２から大問４までは同じ出題形式となります。
文章内容は、脳科学による研究で、孤独が脳にどのような影響があるかを報告しています。脳科学におけるどのような証拠が、理論を支持しているのか読解しましょう。近年の早稲田教育学部では、長文１題は認知科学(心理学＋脳科学＋感性科学)から出題されています。
【重要表現】
confinement 監禁 意味解説例文
assay アセイ 化学分析 意味解説例文
mortality rate 死亡率 意味解説例文
et al. : ラテン語のet alliやet aliaeの略で、「その他（and others）」という意味。研究論文などにおいて、著者が複数名いる時に代表者を挙げて「その他」と併記する。著者全員の名前を連ねて論文が読みづらいものになるのを回避することが出来るが、使用については賛否があり、また何人以上なら使用するか、など議論がある。
encode: エンコードする、符号化する、記号化する。情報、データなどを記号化すること。この文章では生化学的な意味で、遺伝子がタンパク質をコード化すること
早稲田教育学部 2019問題4 完成文
【大問４ 読解問題 完成文】
Even the toughest prisoners fear solitary confinement. There is a growing awareness across the globe that we are facing an epidemic of loneliness. Prolonged social isolation and loneliness can lead to many profound physiological and neuropsychiatric conditions, including depression and heart disease, and to increased mortality rates. But the biological mechanisms underlying the effects of social isolation are poorly understood. Writing in Cell, Zelikowsky et al. reveal a signalling mechanism that acts in several brain regions in mice to drive some of the harmful effects of the stress caused by chronic social isolation.
The authors examined the effects of two weeks of social isolation on the brains and behaviour of male mice (equivalent to more than a year in these conditions for humans). First, the researchers used an array of behavioural tests to compare mice kept in isolation with control mice that had been housed in groups. These assays revealed widespread effects. Compared to control animals, isolated mice showed enhanced aggression and hypersensitivity to diverse stressful stimuli. For example, the socially isolated mice responded more aggressively to an unfamiliar mouse placed in their cage. In another assay, the researchers presented mice with a dark circle that loomed overhead, simulating an approaching predator. Control animals froze in response to the threat, but moved normally after the stressful stimulus was removed, whereas isolated mice remained frozen long after the apparent threat was removed.
Next, Zelikowsky et al. investigated the brain mechanisms underlying this behaviour. In a previous study of fruit flies, the same group had identified the gene Tac as essential for the regulation of aggression induced by social isolation. Rodents have two versions of Tac, which are expressed in various brain regions, including regions associated with social behaviour, anxiety and emotions. Using several independent methods, Zelikowsky and colleagues now found a massive increase in the expression of Tac2 throughout the brain following social isolation.
The gene Tac2 encodes a protein called neurokinin B (NkB), which binds specifically to the receptor Nk3R. The researchers performed a series of experiments to alter NkB signalling in the brain. First, they systemically inhibited NkB signalling in isolated male mice using a drug called osanetant, which inhibits the activity of Nk3R. Administration of osanetant, either throughout the social-isolation period or 20 minutes before behavioural testing, substantially reduced the effects of social isolation on behaviour. Next, the authors genetically upregulated Tac2 expression and simultaneously activated Tac2-expressing neurons in group-housed animals, using specially designed viruses that were injected intravenously but could cross the blood-brain barrier to reach the brain. They found that this genetic manipulation led to group-housed mice behaving in a similar way to those that had been isolated.
This work opens a gateway to much future research. First and foremost, it will be interesting to determine whether TAC3, the human equivalent of Tac2, is involved in mediating the effects of loneliness and social isolation in people. To our knowledge, TAC3 has not yet been directly associated with sociality or social behaviour of any kind in humans. However, it is expressed in the human brain and has shown abnormal gene-expression levels in children with autism-spectrum disorder, which profoundly affects social interaction. The systemic manipulations presented in Zelikowsky and colleagues' paper could be rapidly applied to humans, because osanetant and other NkB inhibitors have already been tested in clinical trials. These drugs could potentially treat anti-social disorders induced by isolation, as well as mood and anxiety disorders.
Finally, one has to wonder: to what extent can we rely on a mouse model of social isolation to truly examine the underlying mechanisms of human loneliness? After all, loneliness and mental isolation are subjective, and a person might feel alone even when surrounded by other people. The traits exhibited by mice under prolonged social isolation greatly resemble those found in humans experiencing solitary confinement, so these animals do provide a good model for studying, this process. What we currently lack are relevant animal models for other forms of human loneliness, such as social withdrawal or antisocial personality disorder. Expanding our research toolbox — for example, by studying various species, including non-social and community-living animals, as well as humans — might bring us closer to understanding the biology of human loneliness.
早稲田教育学部 2019問題4 全訳
【大問４ 読解問題 全訳】
最も屈強な囚人でさえ、独房での監禁を恐れている。私たちが孤独の蔓延に直面しているという認識が世界中で高まりつつある。長期にわたる社会的孤立と孤独は、うつ病や心臓病を含む多くの深刻な生理学的および神経精神医学的状態につながり、死亡率を高める可能性がある。しかし、社会的孤立の影響の根底にある生物学的メカニズムはよく理解されていない。「細胞に書く」（ゼリコスキー その他著）は慢性的な社会的孤立によって引き起こされるストレスの有害な影響のいくつかを駆動させるシグナルのメカニズムをマウスの数カ所の脳領域で明らかにしている。
著者らは、2週間の社会的孤立がオスのマウスの脳と行動に及ぼす影響を調べた（この条件は人間の場合1年以上に相当する）。最初に、研究者たちは一連の行動テストを用いて、隔離されたマウスとグループに収容された対照マウスを比較した。これらの分析により、広範な影響が明らかになった。対照動物と比較して、隔離されたマウスには、多様なストレス刺激に対する強い攻撃性と過敏性が見られた。たとえば、社会的に隔離されたマウスは、ケージに入れられた馴染みのないマウスに対してより積極的に反応した。別の分析では、研究者たちは、頭上に迫り来る捕食動物をシミュレートして暗い円をマウスに提示した。対照動物は脅威に反応して硬直したが、ストレスの多い刺激が取り除かれた後は正常に動くようになった。一方、隔離されたマウスは明らかな脅威が取り除かれた後もかなり長い間硬直したままだった。
次にゼリコフスキーらはこの行動の根底にある脳のメカニズムを調査した。同じ研究グループが以前行ったミバエの研究では、社会的隔離により誘発される攻撃性を調節するのに不可欠な遺伝子Tacを特定した。齧歯類にはTacに2つのバージョンがあり、社会的行動、不安、感情に関連する領域を含むさまざまな脳領域で表れる。いくつかの異なる方法を使用して、ゼリコフスキーと同僚たちは現在、社会的隔離後には脳全体でTac2の発現が大幅に増加することを発見した。
遺伝子Tac2は、受容体Nk3Rに結合するニューロキニンB（NkB）と呼ばれるタンパク質をコードする。研究者らは、脳内でシグナルを送っているNkBを変えるための一連の実験を行った。まず、彼らは、Nk3Rの働きを阻害するオサネタントと呼ばれる薬物を使って、孤立させたオスのマウスの脳内でシグナルを送っているNkBを組織的に阻害した。 オサネタントの投与を、社会的隔離期間の全体を通して行った場合でも行動テスト20分前に行った場合でも、行動における社会的隔離の影響が大幅に減少した。次に、著者らは、静脈内に注入しても脳に到達するよう血液脳関門を通過できる特別に設計されたウイルスを使って、グループに収容したマウスのTac2発現を遺伝的に上方制御し、同時にTac2発現ニューロンを活性化した。彼らは、この遺伝子操作により、グループ飼育のマウスが隔離されたマウスに類似する方法で行動するようになる事を発見した。
この結果は、将来の多くの研究の入り口となる。何よりも、人間の場合のTac2に相当するTAC3が人々の孤独と社会的孤立から引き起こされる影響を媒介するのに関与しているのかどうか判断するのは興味深いことだろう。私たちの知る限り、TAC3はまだ人間のどのような社会性や社会的行動にも直接関係していない。しかし、TAC3は人間の脳で発現し、社会的相互作用に強く影響する自閉症スペクトラム障害の子供において異常な遺伝子発現レベルを示している。オネタントその他のNkB阻害剤の臨床試験は既に行われているので、ゼリコフスキーと同僚の論文で提示された全身操作は、急速に人間に適用されるかもしれない。これらの薬剤には、気分障害や不安障害だけでなく、隔離によって引き起こされる反社会的障害を治療できる可能性があるのだ。
最後に、人間の孤独の根底にあるメカニズムを真に調べるために、社会的に隔離されたマウスのモデルがどの程度頼りになるのか疑ってみなくてはならない。結局のところ、孤独と精神的孤立は主観的なものであり、人は他の人に囲まれていても孤独を感じるかもしれない。長期の社会的隔離下でマウスが示す特性は、孤立した監禁を経験している人間に見られる特性に非常に似ているため、これらの動物はこのプロセスを研究するための良いモデルを提供している。現在不足しているのは、社会的引きこもりや反社会的人格障害など、他の形態の人間の孤独に関連する動物モデルである。私たちの研究ツールボックスを拡張すること、たとえば、人間だけではなく、非社会的動物やコミュニティーを形成して生活する動物など、さまざまな種を研究することで、人間の孤独についての生物学をより理解できるようになるかもしれない。
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