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At least 19 recordsLinked to original sources

The DREAM complex links somatic mutation, lifespan, and disease.

The DREAM complex has emerged as a central repressor of DNA repair, raising questions as to whether such repression exerts long-term effects on human health. Here we establish that DREAM activity significantly impacts lifetime somatic mutation burden, and that such effects are linked to altered lifespan and age-related disease pathology. First, joint profiling of DREAM activity and somatic mutations across a single-cell atlas of 21 mouse tissues shows that cellular niches with lower DREAM activity have decreased mutation rates. Second, DREAM activity predicts the varied lifespans observed across 92 mammals, with low activity marking longer-lived species. Third, reduced DREAM activity in Alzheimer's patients predicts late disease onset and decreased risk for severe neuropathology. Finally, we show DREAM knockout protects against mutation accumulation in vivo, reducing single-base substitutions by 4.2% and insertion/deletions by 19.6% in brains of mice. These findings position DREAM as a key regulator of aging.

Journal Article

The immunochemical complexity of CEA: a golden dream or molecular nightmare?

Carcinoembryonic antigen is only a tumor assoicated antigen and is less clinically useful than the original report suggested. However, the CEA assays in clinical use utilize reagents operationally defined by old criteria. There is now abundant evidence that "CEA" consists of a heterogenous family of related glycoproteins with shared, as well as distinctive, antigenic determinants. Antigenic differences can be demonstrated between some cancer sera "CEA" and various operationally defined tissue "CEA" preparations. Further definition of the biochemical and antigenic characteristics of serum and tumor tissue "CEA" is required in order to determine whether a more tumor specific antigenic determinant can be identified.

Carcinoembryonic Antigen

The TyrRS cascade: circadian gating of neuronal DNA repair and its collapse in aging.

Age-related neurodegenerative diseases are characterized by progressive DNA damage in post-mitotic neurons against a backdrop of deteriorating circadian rhythms, yet the molecular link between these conjoined features of brain aging remains unclear. We propose the TyrRS cascade as that link: a signaling architecture in which the noncanonical nuclear functions of tyrosyl-tRNA synthetase (TyrRS/YARS1) schedule neuronal genome maintenance across the day through three coregulated streams, PARP1-mediated damage sensing, TRIM28/NuRD heterochromatin maintenance, and LIN9/DREAM control of a 67-gene repair archive. The model's central commitment is that the operative variable is oscillation amplitude rather than mean activity. We argue that as serum tyrosine rises with age and circadian amplitude flattens, these insults compound into a double-hit collapse that traps the cascade in a frozen-intermediate state, which bulk-tissue assays misread as elevated mean activity when the oscillation has merely lost its excursion. Placed in dialogue with oscillatory-clearance models of sleep, the cascade and the glymphatic system emerge as complementary, compartment-separated arms of a single sleep-dependent maintenance program that fail together through amplitude collapse, yielding a signature of preserved phase architecture with reduced dynamic range. Reframing neurodegeneration as a scheduling failure rather than a capacity failure carries three translational consequences: Pulsatile, phase-aligned dosing should outperform sustained-release pharmacology, which is predicted to flatten the rhythm it aims to restore; demonstrating target engagement will require phase-resolved rather than single-timepoint measurement; and because both arms fail together, combined restoration of intracellular repair and extracellular clearance should outperform single-arm intervention.

Alzheimer’s disease

Dreams. A developmental and longitudinal perspective.

In young children's dreams the infantile wish appears almost undisguised. Freud used this prototypical expression and representation of the infantile wish in a child's dream to bolster his conviction that the infantile wish was at the genetic root of adults' dreams as well. As development proceeds, a child's dream grows in disguise and complexity. This study of one analysand's dreams at age 5, 13, and 20 addresses the complexity from a longitudinal point of view and attempts to track the infantile wish through all of its developmental vicissitudes and disguises.

Adolescent

The characteristics of EEG activity and the subjective estimation of time during dreams of different structure.

During dreams evoked by stimuli of a certain duration, the EEF was studied in healthy subjects and in patients with implanted electrodes (EEG, ESCoG (electrosubcorticogram), unit activity). Estimation of the temporal structure of the dream was made from the verbal account of the subject. In the case of an unformed dream the duration of the dream was shown to be adequately estimated, the EEF and ESCoG patterns to be rather variable, and correlation between the bioelectric activities of different structures to be nearly absent. Apparently, in these cases, only some of the structures participate in the formation of dreams, which accounts for their unstructure, with no disorder of temporal and spatial relationships, is accompanied by certain orderly rhythms, similar EEG and ESCoG patterns, and a high correlation between bioelectric processes occurring in the structures under study. Dreams with a complex structure, with simultaneous action in different aspects and with major overestimation of their duration, are accompanied by polymorphous EEG and ESCoG patterns. Almost no correlation is observed between bioelectric processes in different structures. Apparently these dreams are associated with independent activities in different structures and, in the verbal account, the subject tends to place the events in a certain temporal order which creates the effect of considerable acceleration of the time flow.

Alpha Rhythm

[Studies of a full night's sleep in patients with absences].

Clinical electro-encephalography and especially the simultaneous recording of EEG values and other physiological parameters can greatly contribute to investigations into the neurophysiological aspects of sleep disturbances in patients suffering from attacks. In the case of absences peak potentials have been found in all phases of sleep, with a reduction in the pattern-like arrangement of the peak potentials and an increase in the irregular spike-and-wave complexes. During the dream phase, however, the peak potentials of these patients were primarily in the form of "patterns" comparable to the situation when they were awake. This evidence of epileptic activity throughout all sleep phases of patients suffering from absences makes it necessary to give anticonvulsive drugs in three doses distributed evenly over the entire day.

Child

DREAMS illuminates spatial DNA and RNA modification landscapes.

DNA and RNA modifications regulate gene expression and RNA processing, but their spatial organization in complex tissues remains elusive. Here we developed DNA RNA Elements Areal Mass Spectrometry (DREAMS), a mass spectrometry imaging platform that spatially maps diverse nucleic acid modifications simultaneously. Applying DREAMS to TET-deficient mouse brains (Tet1Δ/Δ and triple Tet1/2/3Δ/Δ), we uncover TET1's unexpected role in modulating N1-methyladenosine (m1A), a pivotal RNA modification. While DREAMS reveals broad modification landscapes altered across TET knockouts, we identify TET1-mediated changes in m1A that correlate with transcriptome alterations. Our work establishes DREAMS as a transformative tool for spatial epigenomics/epitranscriptomics and suggests that TET enzymes could influence multiple DNA and RNA modifications with potential gatekeeping roles in nucleic acid regulation.

Animals

Evidence from epileptic patients on the role of the right hemisphere in REM sleep.

Eight highly selected epileptic patients found to have lasting right temporal or temporooccipital rhythmic focal activity during night sleep were reassessed following remission which occurred between a few days and 7 years after the initial finding. In polysomnographic EEG recording, when the patients had extensive epileptic discharges in the right temporal and temporo-occipital regions, a prolonged period of REM sleep occurred (34.1 +/- 7.06% of total sleep time). Following remission, however, disproportion had returned to normal (20.4 +/- 1.75%). These results confirm that intensive focal epileptic activity in the temporal and temporooccipital regions of the right hemisphere during sleep facilitate REM sleep thus indicating a dominant role for the right hemisphere in REM sleep and dreaming.

Adult

Comparison of auras and triggering factors in epilepsy.

Case reports of five patients are presented, each with a specific aura at the onset of the seizures. All of these patients' had seizures during the waking state. Their auras were carefully replicated and presented to the patients under various conditions. The presentation of the auras evoked neither clinical nor EEG evidence of seizures. A sixth patient had seizures only when asleep which were preceded by vivid nightmares. Since the seizures occurred only when the patient was asleep, we considered that the seizures could be reflex in nature and evoked by a dream. Replication of the dream, however, did not evoke clinical or EEG evidence of epilepsy. The dreams, therefore, were auras or a part of the seizure complex.

Acoustic Stimulation

The devil-priest syndrome.

Men frequently relate to women as either "sanctified" and hence, asexual, or as sexual, and therefore "degraded." A case is presented demonstrating a similar finding in a woman. The uncovering of the "Devil-Priest Syndrome" during psychotherapy is described. Some speculations as to the significance of this finding in the understanding of the psychodynamics of sexuality are included.

Adult