The Perseus computational platform for comprehensive analysis of (prote)omics data

Nature Methods, Год журнала: 2016, Номер 13(9), С. 731 - 740

Опубликована: Июнь 27, 2016

Язык: Английский

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Ubiquitin Ligases: Structure, Function, and Regulation

Annual Review of Biochemistry, Год журнала: 2017, Номер 86(1), С. 129 - 157

Опубликована: Апрель 4, 2017

Ubiquitin E3 ligases control every aspect of eukaryotic biology by promoting protein ubiquitination and degradation. At the end a three-enzyme cascade, ubiquitin mediate transfer from an E2 ubiquitin-conjugating enzyme to specific substrate proteins. Early investigations E3s RING (really interesting new gene) HECT (homologous E6AP carboxyl terminus) types shed light on their enzymatic activities, general architectures, degron-binding modes. Recent studies have provided deeper mechanistic insights into catalysis, activation, regulation. In this review, we summarize current progress in structure-function as well exciting discoveries novel classes diverse recognition mechanisms. Our increased understanding ligase function regulation has rationale for developing E3-targeting therapeutics treatment human diseases.

Язык: Английский

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Circadian rhythm disruption and mental health

Translational Psychiatry, Год журнала: 2020, Номер 10(1)

Опубликована: Янв. 23, 2020

Abstract Circadian rhythms are internal manifestations of the solar day that permit adaptations to predictable environmental temporal changes. These ~24-h controlled by molecular clockworks within brain reset daily precisely 24 h exposure light–dark cycle. Information from master clock in mammalian hypothalamus conveys information entire body via humoral and neural communication. A bidirectional relationship exists between mood disorders circadian rhythms. Mood often associated with disrupted clock-controlled responses, such as sleep cortisol secretion, whereas disruption jet lag, night-shift work, or artificial light at night, can precipitate exacerbate affective symptoms susceptible individuals. Evidence suggests strong associations mental health, but only recently have studies begun discover direct interactions system regulation. This review provides an overview behavioral health psychiatry. The focus this is delineating role on using human night shift studies, well lag identify links. We also animal models responses. Lastly, we propose low-cost lifestyle changes improve presumably health.

Язык: Английский

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Circadian time signatures of fitness and disease

Science, Год журнала: 2016, Номер 354(6315), С. 994 - 999

Опубликована: Ноя. 24, 2016

Biological clocks are autonomous anticipatory oscillators that play a critical role in the organization and information processing from genome to whole organisms. Transformative advances into clock system have opened insight fundamental mechanisms through which program energy transfer sunlight organic matter potential energy, addition cell development genotoxic stress response. The identification of nearly every single body raises questions as how this gives rise rhythmic physiology multicellular organisms environmental signals entrain geophysical time. Here, we consider understanding regulatory networks emergent give type-specific functions within tissues affect homeostasis.

Язык: Английский

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Circadian regulation of glucose, lipid, and energy metabolism in humans

Metabolism, Год журнала: 2017, Номер 84, С. 11 - 27

Опубликована: Дек. 2, 2017

Язык: Английский

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Clocking in to immunity

Nature reviews. Immunology, Год журнала: 2018, Номер 18(7), С. 423 - 437

Опубликована: Апрель 16, 2018

Язык: Английский

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Brain disorders? Not really: Why network structures block reductionism in psychopathology research

Behavioral and Brain Sciences, Год журнала: 2018, Номер 42

Опубликована: Янв. 24, 2018

Abstract In the past decades, reductionism has dominated both research directions and funding policies in clinical psychology psychiatry. The intense search for biological basis of mental disorders, however, not resulted conclusive reductionist explanations psychopathology. Recently, network models have been proposed as an alternative framework analysis which disorders arise from causal interplay between symptoms. this target article, we show that conceptualization can help explain why approaches psychiatry are on wrong track. First, symptom networks preclude identification a common cause symptomatology with neurobiological condition; networks, there is no such cause. Second, relations depend content states and, such, feature intentionality. Third, strength highly likely to partially cultural historical contexts well external mechanisms environment. Taken together, these properties suggest that, if indeed causally related symptoms, accounts cannot achieve level success associated disease modern medicine. As strategy, propose interpret structures terms D. C. Dennett's (1987) notion real patterns , instead being reducible basis, psychological factors deeply intertwined feedback loops. This suggests neither nor levels claim or explanatory priority, holistic strategy necessary progress study disorders.

Язык: Английский

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Clockophagy is a novel selective autophagy process favoring ferroptosis

Science Advances, Год журнала: 2019, Номер 5(7)

Опубликована: Июль 5, 2019

Autophagy-dependent cell death may hold the key to understanding molecular basis of ferroptosis.

Язык: Английский

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Estrogens in Male Physiology

Physiological Reviews, Год журнала: 2017, Номер 97(3), С. 995 - 1043

Опубликована: Май 25, 2017

Estrogens have historically been associated with female reproduction, but work over the last two decades established that estrogens and their main nuclear receptors (ESR1 ESR2) G protein-coupled estrogen receptor (GPER) also regulate male reproductive nonreproductive organs. 17β-Estradiol (E2) is measureable in blood of men males other species, rete testis fluids, E2 reaches concentrations normally found only females some species nanomolar estrone sulfate are semen. Aromatase, which converts androgens to estrogens, expressed Leydig cells, seminiferous epithelium, Early studies showed binding numerous tissues, ESR1 ESR2 each show unique distributions actions males. Exogenous treatment produced pathologies laboratory animals men, especially during development, transgenic mice compromised signaling demonstrated an role normal physiology. Efferent ductules epididymal functions dependent on through ESR1, whose loss impaired ion transport water reabsorption, resulting abnormal sperm. Loss or aromatase produces effects targets such as brain, adipose, skeletal muscle, bone, cardiovascular, immune tissues. Expression GPER extensive tracts, suggesting a possible for this reproduction. Recent evidence indicates membrane has critical roles Thus important physiological regulators males, future may reveal additional various target

Язык: Английский

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Circadian Rhythms and Sleep in Drosophila melanogaster

Genetics, Год журнала: 2017, Номер 205(4), С. 1373 - 1397

Опубликована: Март 30, 2017

The advantages of the model organism Drosophila melanogaster, including low genetic redundancy, functional simplicity, and ability to conduct large-scale screens, have been essential for understanding molecular nature circadian (∼24 hr) rhythms, continue be valuable in discovering novel regulators rhythms sleep. In this review, we discuss current these interrelated biological processes wider implications research. Clock genes period timeless were first discovered screens developed 1970s. Feedback on their own transcription forms core clock, accurately timed expression, localization, post-transcriptional modification, function is thought critical maintaining cycle. Regulators, several phosphatases kinases, act different steps feedback loop ensure strong rhythms. Approximately 150 neurons fly brain that contain components clock together translate intracellular cycling into rhythmic behavior. We how groups serve functions allowing clocks entrain environmental cues, driving behavioral outputs at times day, flexible responses conditions. neuropeptide PDF provides an important signal synchronize neurons, although details accomplishes are still being explored. Secreted signals from also influence other tissues. SLEEP is, part, regulated by which ensures appropriate timing sleep, but amount quality sleep determined mechanisms a homeostatic balance between wake. Flies useful identifying large set genes, molecules, neuroanatomic loci regulating amount. Conserved aspects regulation flies mammals include wake-promoting roles catecholamine neurotransmitters involvement hypothalamus-like regions, regions implicated less clear parallels. Sleep subject factors such as food availability, stress, social environment. beginning understand identified molecules interact with each other, environment, regulate researchers can take advantage increasing mechanistic behaviors, learning memory, courtship, aggression, loss impacts behaviors. thus remain tool both discovery deep

Язык: Английский

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