DCC
Netrin receptor DCC precursor (Colorectal cancer suppressor) (Immunoglobulin superfamily DCC subclass member 1) (Tumor suppressor protein DCC) [IGDCC1]
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Mechanisms establishing higher-order chromosome structures and their roles in gene regulation are elusive. We analyzed chromosome architecture during nematode X chromosome dosage compensation, which represses transcription via a dosage-compensation condensin complex (DCC) that binds hermaphrodite Xs and establishes megabase-sized topologically associating domains (TADs). We show that DCC binding at high-occupancy sites (rex sites) defines eight TAD boundaries. Single rex deletions disrupted boundaries, and single insertions created new boundaries, demonstrating that a rex site is necessary and sufficient to define DCC-dependent boundary locations. Deleting eight rex sites (8rexΔ) recapitulated TAD structure of DCC mutants, permitting analysis when chromosome-wide domain architecture was disrupted but most DCC binding remained. 8rexΔ animals exhibited no changes in X expression and lacked dosage-compensation mutant phenotypes. Hence, TAD boundaries are neither the cause nor the consequence of DCC-mediated gene repression. Abrogating TAD structure did, however, reduce thermotolerance, accelerate aging, and shorten lifespan, implicating chromosome architecture in stress responses and aging.
MeSH Terms
- Adenosine Triphosphatases
- Animals
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- DNA-Binding Proteins
- Dosage Compensation, Genetic
- Gene Expression Regulation
- Longevity
- Multiprotein Complexes
- X Chromosome
Keywords
- X chromosome dosage compensation
- aging
- condensin
- gene expression
- higher-order chromosome structure
- lifespan
- proteotoxic stress
- topologically associating domains
Recent studies showed that functional connectivity (FC) in the human brain is not static but can dynamically change across time within time scales of seconds to minutes. This study introduces a new statistical method called the copula time-varying correlation for dynamic functional connectivity (dFC) analysis from functional magnetic resonance imaging (fMRI) data. Compared to other state-of-the-art statistical measures of dynamic correlation such as the dynamic conditional correlation (DCC), the proposed method can be effectively applied to data having asymmetric or non-normal distributions. Numerical simulations were conducted under various kinds of time-varying correlations and distributions, and it was demonstrated that the proposed method was superior to the DCC-based method for asymmetric and non-normal distributions. FMRI data of 138 human participants watching a Pixar animated movie were analyzed by the proposed method based on five a priori selected brain regions in the cortex. Based on statistical group analysis results, it was discovered that (1) the correlation between the left temporoparietal junction (LTPJ) and the primary visual cortex (V1) and the correlation between the dorsal posterior cingulate cortex (dPCC) and V1 were significantly higher for older age groups (5yo-Adult) more often than for younger age groups (3yo-4yo), and (2) the right temporoparietal junction (RTPJ), LTPJ, and dPCC were significantly correlated in all age groups at most of the scanning time periods.
MeSH Terms
- Adult
- Aging
- Cerebral Cortex
- Child
- Child, Preschool
- Connectome
- Female
- Humans
- Image Processing, Computer-Assisted
- Magnetic Resonance Imaging
- Male
- Models, Statistical
- Statistical Distributions
- Theory of Mind
- Time Factors
Keywords
- Aging
- Copula
- Dynamic conditional correlation
- Dynamic functional connectivity
- FMRI
- Generalized autoregressive conditional heteroscedastic (GARCH)
- Posterior cingulate cortex
- Theory-of-mind (ToM)
The answer to current social and health needs of people aged over 60 are the multidirectional and carefully planned, comprehensive activation and rehabilitation activities carried out as part of Daycare Centres (DCC). The aim of creating and the functioning of DCCs deployed all over Poland is to improve the health and psychophysical fitness of this group of people. Health factors and psychophysical fitness determine the ability to live independently, both today, and later in life. The objective of the study was to assess the impact of comprehensive ambulatory rehabilitation, including tailored endurance training preceded by an ergospirometry test, on indicators demonstrating the ability to live independently and the risk ratio of future health problems in the elderly. 60 people participating in a rehabilitation cycle implemented as part of the services provided to patients aged over 60 in the DCC of the Witold Chodźko Institute of Rural Medicine (IMW) in Lublin comprised the sample. The tests were carried out in the test-retest model on the first and last day of the kinesiotherapy cycle. Patients were tested using standardized Barthel, I-ADL and VES-13 questionnaires. The rehabilitation programme applied included systemic kinesiotherapy (endurance training) with a load determined according to individual exercise capacity, determined on the basis of a ergospirometry test, and varied rehabilitation activities resulting from the condition of the locomotor system, as provided for under the project. After completing the rehabilitation cycle, patients obtained higher results in comparison to the tests carried out before the beginning of the cycle in the Barthel index used to measure functional efficiency (Z = 5.41; p = 0.001), as well as lower in the I-ADL scale used to test the degree of dependence on the help of others when performing complex activities of everyday life (Z = 2.63; p = 0.009) and in VES-13 scale used to assess the risk of geriatric health problems (Z = 5.47; p = 0.001). As the result of the use of comprehensive rehabilitation, including obligatory endurance training, desired changes were achieved in terms of fitness and independence in performing advanced daily activities and reducing the risk of geriatric health problems.
MeSH Terms
- Activities of Daily Living
- Aged
- Aged, 80 and over
- Aging
- Female
- Humans
- Independent Living
- Male
- Middle Aged
- Outpatients
- Poland
- Rehabilitation Centers
- Surveys and Questionnaires
Keywords
- Barthel index
- ES-13
- I-ADL
- endurance training
- independent existence
- rehabilitation
- seniors
{{medline-entry |title=Mesocorticolimbic Connectivity and Volumetric Alterations in [i]DCC[/i] Mutation Carriers. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29712788 |abstract=The axon guidance cue receptor DCC (deleted in colorectal cancer) plays a critical role in the organization of mesocorticolimbic pathways in rodents. To investigate whether this occurs in humans, we measured (1) anatomical connectivity between the substantia nigra/ventral tegmental area (SN/VTA) and forebrain targets, (2) striatal and cortical volumes, and (3) putatively associated traits and behaviors. To assess translatability, morphometric data were also collected in [i]Dcc[/i]-haploinsufficient mice. The human volunteers were 20 [i]DCC[/i] mutation carriers, 16 [i]DCC[/i] relatives, and 20 [i]DCC[/i] unrelated healthy volunteers (UHVs; 28 females). The mice were 11 [i]Dcc[/i] and 16 wild-type C57BL/6J animals assessed during adolescence and adulthood. Compared with both control groups, the human [i]DCC[/i] carriers exhibited the following: (1) reduced anatomical connectivity from the SN/VTA to the ventral striatum [[i]DCC[/i] : [i]p[/i] = 0.0005, [i]r[/i]([i]effect size[/i]) = 0.60; UHV: [i]p[/i] = 0.0029, [i]r[/i] = 0.48] and ventral medial prefrontal cortex ([i]DCC[/i] : [i]p[/i] = 0.0031, [i]r[/i] = 0.53; UHV: [i]p[/i] = 0.034, [i]r[/i] = 0.35); (2) lower novelty-seeking scores ([i]DCC[/i] : [i]p[/i] = 0.034, [i]d[/i] = 0.82; UHV: [i]p[/i] = 0.019, [i]d[/i] = 0.84); and (3) reduced striatal volume ([i]DCC[/i] : [i]p[/i] = 0.0009, [i]d[/i] = 1.37; UHV: [i]p[/i] = 0.0054, [i]d[/i] = 0.93). Striatal volumetric reductions were also present in [i]Dcc[/i] mice, and these were seen during adolescence ([i]p[/i] = 0.0058, [i]d[/i] = 1.09) and adulthood ([i]p[/i] = 0.003, [i]d[/i] = 1.26). Together these findings provide the first evidence in humans that an axon guidance gene is involved in the formation of mesocorticolimbic circuitry and related behavioral traits, providing mechanisms through which [i]DCC[/i] mutations might affect susceptibility to diverse neuropsychiatric disorders. Opportunities to study the effects of axon guidance molecules on human brain development have been rare. Here, the identification of a large four-generational family that carries a mutation to the axon guidance molecule receptor gene, [i]DCC[/i], enabled us to demonstrate effects on mesocorticolimbic anatomical connectivity, striatal volumes, and personality traits. Reductions in striatal volumes were replicated in [i]DCC[/i]-haploinsufficient mice. Together, these processes might influence mesocorticolimbic function and susceptibility to diverse neuropsychiatric disorders. |mesh-terms=* Adult
- Aging
- Animals
- Axons
- DCC Receptor
- Exploratory Behavior
- Female
- Heterozygote
- Humans
- Limbic System
- Magnetic Resonance Imaging
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Middle Aged
- Neural Pathways
- Personality Disorders
- Prefrontal Cortex
- Substance-Related Disorders
- Substantia Nigra
- Ventral Tegmental Area
- Young Adult
|keywords=* axon guidance
- brain morphometry
- diffusion MRI
- genetics
- nicotine
- personality
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956985 }}
Adolescence is a period during which the medial prefrontal cortex (mPFC) undergoes significant remodeling. The netrin-1 receptor, deleted in colorectal cancer (DCC), controls the extent and organization of mPFC dopamine connectivity during adolescence and in turn directs mPFC functional and structural maturation. Dcc haploinsufficiency leads to increased mPFC dopamine input, which causes improved cognitive processing and resilience to behavioral effects of stimulant drugs of abuse. Here we examine the effects of Dcc haploinsufficiency on the dynamic expression of dopamine receptors in forebrain targets of C57BL6 mice. We conducted quantitative receptor autoradiography experiments with [ H]SCH-23390 or [ H]raclopride to characterize D1 and D2 receptor expression in mPFC and striatal regions in male Dcc haploinsufficient and wild-type mice. We generated autoradiograms at early adolescence (PND21±1), mid-adolescence (PND35±2), and adulthood (PND75±15). C57BL6 mice exhibit overexpression and pruning of D1, but not D2, receptors in striatal regions, and a lack of dopamine receptor pruning in the mPFC. We observed age- and region-specific differences in D1 and D2 receptor density between Dcc haploinsufficient and wild-type mice. Notably, neither group shows the typical pattern of mPFC dopamine receptor pruning in adolescence, but adult haploinsufficient mice show increased D2 receptor density in the mPFC. These results show that DCC receptors contribute to the dynamic refinement of D1 and D2 receptor expression in striatal regions across adolescence. The age-dependent expression of dopamine receptor in C57BL6 mice shows marked differences from previous characterizations in rats.
MeSH Terms
- Aging
- Animals
- Corpus Striatum
- DCC Receptor
- Haploinsufficiency
- Male
- Mice
- Mice, Inbred C57BL
- Nucleus Accumbens
- Prefrontal Cortex
- Receptors, Cell Surface
- Receptors, Dopamine D1
- Receptors, Dopamine D2
- Tumor Suppressor Proteins
Keywords
- DCC
- adolescence
- guidance cues
- netrin-1
- prefrontal cortex
- receptor pruning
{{medline-entry |title=Potential effect of mechano growth factor E-domain peptide on axonal guidance growth in primary cultured cortical neurons of rats. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27863093 |abstract=Establishing appropriate synaptic connections and plasticity is a critical need in neuronal regeneration and development. Mechano growth factor (MGF) and its C-terminal E-domain peptide with 24 amino acids, MGF-Ct24E, are potential neuroprotective agents. Our preliminary study indicates that Netrin-1 can guide axonal growth and its expression is sensitive to MGF, but how MGF regulates the expression of Netrin-1 and its receptor DCC is still unclear. Here, we investigate the effect of MGF-Ct24E on the expression of Netrin-1 and DCC in primary cultured cortical neurons in vitro and the adult rat brain in vivo. MTT assay shows that MGF-Ct24E can significantly protect primary cortical neurons against nerve injury. There is a significant increase in axonal elongation after MGF-Ct24E treatment at concentrations of 0.5 and 1.0 μg/ml. Real-time polymerase chain reaction assay indicates that MGF-Ct24E can effectively promote the expression of Netrin-1 and DCC in primary cultured cortical neurons. To identify the certain mechanism of MGF-Ct24E on neuronal guidance and growth, adult rats are subjected to intramuscular injection of MGF-Ct24E after traumatic brain injury. Rats injected with MGF-Ct24E start eating and drinking within 14 days, indicating that MGF-Ct24E can promote rehabilitation. HE staining and immunohistochemistry assays of brain section slices reveal that MGF-Ct24E treatment can significantly inhibit the haemorrhage of traumatic brain injury and promote expression of Netrin-1. Further investigation of protein expression by Western blot assay shows that MGF-Ct24E promotes expression of Netrin-1 and DCC after nerve injury. MGF-Ct24E can effectively improve axonal guidance through upregulation of Netrin-1/DCC signalling in neuronal regeneration. Copyright © 2016 John Wiley