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RNA modifications have emerged as an additional layer of regulatory complexity governing the function of almost all species of RNA. N 6 -methyladenosine (m 6 A), the addition of methyl groups to adenine residues, is the most abundant and well understood RNA modification. The current review discusses the regulatory mechanisms governing m 6 A, how this influences neuronal development and function and how aberrant m 6 A signaling may contribute to neurological disease. M 6 A is known to regulate the stability of mRNA, the processing of microRNAs and function/processing of tRNAs among other roles. The development of antibodies against m 6 A has facilitated the application of next generation sequencing to profile methylated RNAs in both health and disease contexts, revealing the extent of this transcriptomic modification. The mechanisms by which m 6 A is deposited, processed, and potentially removed are increasingly understood. Writer enzymes include METTL3 and METTL14 while YTHDC1 and YTHDF1 are key reader proteins, which recognize and bind the m 6 A mark. Finally, FTO and ALKBH5 have been identified as potential erasers of m 6 A, although there in vivo activity and the dynamic nature of this modification requires further study. M 6 A is enriched in the brain and has emerged as a key regulator of neuronal activity and function in processes including neurodevelopment, learning and memory, synaptic plasticity, and the stress response. Changes to m 6 A have recently been linked with Schizophrenia and Alzheimer disease. Elucidating the functional consequences of m 6 A changes in these and other brain diseases may lead to novel insight into disease pathomechanisms, molecular biomarkers and novel therapeutic targets.

Human behaviour is lopsided. When cradling a newborn child, most of us cradle the infant to the left. When kissing a lover, we tend to tilt our head to the right. Our brains influence our actions and habits more than we know.

With new and advanced technology, human exploration has reached outside of the Earth’s boundaries. There are plans for reaching Mars and the satellites of Jupiter and Saturn, and even to build a permanent base on the Moon. However, human beings have evolved on Earth with levels of gravity and radiation that are very different from those that we have to face in space. These issues seem to pose a significant limitation on exploration. Although there are plausible solutions for problems related to the lack of gravity, it is still unclear how to address the radiation problem. Several solutions have been proposed, such as passive or active shielding or the use of specific drugs that could reduce the effects of radiation. Recently, a method that reproduces a mechanism similar to hibernation or torpor, known as synthetic torpor, has started to become possible. Several studies show that hibernators are resistant to acute high-dose-rate radiation exposure. However, the underlying mechanism of how this occurs remains unclear, and further investigation is needed. Whether synthetic hibernation will also protect from the deleterious effects of chronic low-dose-rate radiation exposure is currently unknown. Hibernators can modulate their neuronal firing, adjust their cardiovascular function, regulate their body temperature, preserve their muscles during prolonged inactivity, regulate their immune system, and most importantly, increase their radioresistance during the inactive period. According to recent studies, synthetic hibernation, just like natural hibernation, could mitigate radiation-induced toxicity. In this review, we see what artificial hibernation is and how it could help the next generation of astronauts in future interplanetary missions.

Brain function networks (BFN) are widely used in the diagnosis of electroencephalography (EEG)-based major depressive disorder (MDD). Typically, a BFN is constructed by calculating the functional connectivity (FC) between each pair of channels. However, it ignores high-order relationships (e.g., relationships among multiple channels), making it a low-order network. To address this issue, a novel classification framework, based on matrix variate normal distribution (MVND), is proposed in this study. The framework can simultaneously generate high- and low-order BFN and has a distinct mathematical interpretation. Specifically, the entire time series is first divided into multiple epochs. For each epoch, a BFN is constructed by calculating the phase lag index (PLI) between different EEG channels. The BFNs are then used as samples, maximizing the likelihood of MVND to simultaneously estimate its low-order BFN (Lo-BFN) and high-order BFN (Ho-BFN). In addition, to solve the problem of the excessively high dimensionality of Ho-BFN, Kronecker product decomposition is used for dimensionality reduction while retaining the original high-order information. The experimental results verified the effectiveness of Ho-BFN for MDD diagnosis in 24 patients and 24 normal controls. We further investigated the selected discriminative Lo-BFN and Ho-BFN features and revealed that those extracted from different networks can provide complementary information, which is beneficial for MDD diagnosis.

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease. Genome-wide analysis identifies variants associated with the volume of seven different subcortical brain regions defined by magnetic resonance imaging. Implicated genes are involved in neurodevelopmental and synaptic signaling pathways.

Objective: The objective of this study is to summarize and analyze the brain signal patterns of empathy for pain caused by facial expressions of pain utilizing activation likelihood estimation, a meta-analysis method. Data Sources: Studies concerning the brain mechanism were searched from the Science Citation Index, Science Direct, PubMed, DeepDyve, Cochrane Library, SinoMed, Wanfang, VIP, China National Knowledge Infrastructure, and other databases, such as SpringerLink, AMA, Science Online, Wiley Online, were collected. A time limitation of up to 13 December 2016 was applied to this study. Data Selection: Studies presenting with all of the following criteria were considered for study inclusion: Use of functional magnetic resonance imaging, neutral and pained facial expression stimuli, involvement of adult healthy human participants over 18 years of age, whose empathy ability showed no difference from the healthy adult, a painless basic state, results presented in Talairach or Montreal Neurological Institute coordinates, multiple studies by the same team as long as they used different raw data. Outcome Measures: Activation likelihood estimation was used to calculate the combined main activated brain regions under the stimulation of pained facial expression. Results: Eight studies were included, containing 178 subjects. Meta-analysis results suggested that the anterior cingulate cortex (BA32), anterior central gyrus (BA44), fusiform gyrus, and insula (BA13) were activated positively as major brain areas under the stimulation of pained facial expression. Conclusion: Our study shows that pained facial expression alone, without viewing of painful stimuli, activated brain regions related to pain empathy, further contributing to revealing the brain's mechanisms of pain empathy.

Key Points Childhood maltreatment (specifically, physical, sexual and emotional abuse, and physical and emotional neglect) exerts a prepotent influence on trajectories of child brain development and constitutes a major risk factor for adult psychopathology. Brain alterations resulting from maltreatment are highly specific, depend on the type and timing of exposure, and probably were once phenotypic adaptations that enhanced species survival and reproductive success but are now associated with substantial medical and psychiatric disadvantages. Maltreatment reduces the volume of the hippocampus (particularly in adults), as well as the volume of anterior cingulate and ventromedial and dorsomedial cortices; affects the development of key fibre tracts (including the corpus callosum, superior longitudinal fasciculus, uncinate fasciculus and cingulum bundle); and appears to alter the development of sensory systems that process and convey stressful experiences. This Review reveals consistent reports of augmented amygdala response to threatening stimuli, diminished ventral striatal response to anticipation or receipt of reward, diminished connectivity between prefrontal regions and the amygdala, and increased volume and network centrality of the precuneus in maltreated individuals. Maltreated and non-maltreated individuals with the same primary psychiatric diagnoses differ clinically, neurobiologically and genetically, such that maltreated individuals seem to represent distinct ecophenotypes of established psychiatric disorders. Thus, maltreatment may be an unrecognized confound in psychiatric neuroimaging studies. Maltreatment-associated brain changes are frequently reported in resilient individuals who show no past or current symptoms of psychopathology. Other neurobiological or molecular alterations are probably present that enable these individuals to effectively compensate for stress-related neurobiological alterations. Adverse childhood experiences have a wide range of effects on the structure, function and connectivity of the developing brain. Teicher et al . suggest that such changes might reflect adaptive modifications that, in some susceptible individuals, could contribute to psychopathology. Maltreatment-related childhood adversity is the leading preventable risk factor for mental illness and substance abuse. Although the association between maltreatment and psychopathology is compelling, there is a pressing need to understand how maltreatment increases the risk of psychiatric disorders. Emerging evidence suggests that maltreatment alters trajectories of brain development to affect sensory systems, network architecture and circuits involved in threat detection, emotional regulation and reward anticipation. This Review explores whether these alterations reflect toxic effects of early-life stress or potentially adaptive modifications, the relationship between psychopathology and brain changes, and the distinction between resilience, susceptibility and compensation.

Physicians, health care workers, members of the clergy, and laypeople throughout the world have accepted fully that a person is dead when his or her brain is dead. Although the widespread use of mechanical ventilators and other advanced critical care services have transformed the course of terminal neurologic disorders. Vital functions can now be maintained artificially for a long period of time after the brain has ceased to function. There is a need to diagnose brain death with utmost accuracy and urgency because of an increased awareness amongst the masses for an early diagnosis of brain death and the requirements of organ retrieval for transplantation. Physicians need not be, or consult with, a neurologist or neurosurgeon in order to determine brain death. The purpose of this review article is to provide health care providers in India with requirements for determining brain death, increase knowledge amongst health care practitioners about the clinical evaluation of brain death, and reduce the potential for variations in brain death determination policies and practices amongst facilities and practitioners. Process for brain death certification has been discussed under the following: 1. Identification of history or physical examination findings that provide a clear etiology of brain dysfunction. 2. Exclusion of any condition that might confound the subsequent examination of cortical or brain stem function. 3. Performance of a complete neurological examination including the standard apnea test and 10 minute apnea test. 4. Assessment of brainstem reflexes. 5. Clinical observations compatible with the diagnosis of brain death. 6. Responsibilities of physicians. 7. Notify next of kin. 8. Interval observation period. 9. Repeat clinical assessment of brain stem reflexes. 10. Confirmatory testing as indicated. 11. Certification and brain death documentation. DOI: 10.4103/0972-5229.53108

The fusion of patterned cerebral organoids into more complex structures enables modeling of inter-regional processes such as neuronal migration. Human brain development involves complex interactions between different regions, including long-distance neuronal migration or formation of major axonal tracts. Different brain regions can be cultured in vitro within 3D cerebral organoids, but the random arrangement of regional identities limits the reliable analysis of complex phenotypes. Here, we describe a coculture method combining brain regions of choice within one organoid tissue. By fusing organoids of dorsal and ventral forebrain identities, we generate a dorsal–ventral axis. Using fluorescent reporters, we demonstrate CXCR4-dependent GABAergic interneuron migration from ventral to dorsal forebrain and describe methodology for time-lapse imaging of human interneuron migration. Our results demonstrate that cerebral organoid fusion cultures can model complex interactions between different brain regions. Combined with reprogramming technology, fusions should offer researchers the possibility to analyze complex neurodevelopmental defects using cells from neurological disease patients and to test potential therapeutic compounds.