A5036526059- Pain Mechanisms and Treatments
- Sirtuins and Resveratrol in Medicine
- Obsessive-Compulsive Spectrum Disorders
- Neurobiology and Insect Physiology Research
- Neurogenesis and neuroplasticity mechanisms
- Zebrafish Biomedical Research Applications
- Neuroscience and Neuropharmacology Research
- Autism Spectrum Disorder Research
- PARP inhibition in cancer therapy
- Muscle activation and electromyography studies
- Behavioral and Psychological Studies
- Spinal Cord Injury Research
- Myofascial pain diagnosis and treatment
- Calcium signaling and nucleotide metabolism
- Anesthesia and Neurotoxicity Research
- Adipose Tissue and Metabolism
- Chromosomal and Genetic Variations
- Cancer, Stress, Anesthesia, and Immune Response
- Children's Physical and Motor Development
- Trypanosoma species research and implications
- Motor Control and Adaptation
- NF-κB Signaling Pathways
- RNA Research and Splicing
- Insect symbiosis and bacterial influences
- Chromatin Remodeling and Cancer
Rutgers, The State University of New Jersey
2014-2025
Article25 May 2016Open Access Source DataTransparent process SIRT7 promotes genome integrity and modulates non-homologous end joining DNA repair Berta N Vazquez Department of Genetics, Human Genetics Institute New Jersey, Rutgers University, Piscataway, NJ, USA Search for more papers by this author Joshua K Thackray Nicolas G Simonet Chromatin Biology Laboratory, Cancer Epigenetics Program (PEBC), Bellvitge Biomedical Research (IDIBELL), Barcelona, Spain Noriko Kane-Goldsmith Paloma...
Highlights•Recurrent de novo variants identify a new high-confidence TD risk gene: CELSR3•Genes involved in cell polarity are more likely to be disrupted by variants•De sequence may carry simplex families, female probands•De CNVs occur 2 3 times often probands than matched controlsSummaryWe previously established the contribution of damaging Tourette disorder (TD) through whole-exome sequencing 511 trios. Here, we an additional 291 trios and analyze combined set 802 We observe...
Tourette disorder (TD) is poorly understood, despite affecting 1/160 children. A lack of animal models possessing construct, face, and predictive validity hinders progress in the field. We used CRISPR/Cas9 genome editing to generate mice with mutations orthologous human de novo variants two high-confidence genes, CELSR3 WWC1 . Mice Celsr3 Wwc1 exhibit cognitive and/or sensorimotor behavioral phenotypes consistent TD. Sensorimotor gating deficits, as measured by acoustic prepulse inhibition,...
HP1 is a structural component of heterochromatin. Mammalian isoforms HP1α, HP1β, and HP1γ play different roles in genome stability, but their precise role heterochromatin structure unclear. Analysis Hp1α−/−, Hp1β−/−, Hp1γ−/− MEFs show that proteins have both redundant unique functions within pericentric (PCH) also act globally throughout the genome. HP1α confines H4K20me3 H3K27me3 to regions PCH, while its absence results global hyper-compaction chromatin associated with specific pattern...
Oncogenic mutations in BRAF are believed to initiate serrated colorectal cancers; however, the mechanisms of BRAF-driven colon cancer unclear. We find that oncogenic paradoxically suppresses stem cell renewal and instead promotes differentiation. Correspondingly, tumor formation is inefficient mouse models cancer. By reducing levels differentiation via genetic manipulation either two distinct differentiation-promoting factors (Smad4 or Cdx2), activity restored BRAFV600E intestines, capacity...
Long interspersed elements-1 (LINE-1, L1) are retrotransposons that hold the capacity of self-propagation in genome with potential mutagenic outcomes. How somatic cells restrict L1 activity and how this process becomes dysfunctional during aging cancer is poorly understood. L1s enriched at lamin-associated domains, heterochromatic regions nuclear periphery. Whether association necessary for their repression has been elusive. Here we show sirtuin family member SIRT7 participates epigenetic...
Skull development coincides with the onset of cerebrospinal fluid (CSF) circulation, brain-CSF perfusion, and meningeal lymphangiogenesis, processes essential for brain waste clearance. How these are affected by craniofacial disorders such as craniosynostosis poorly understood. We report that raised intracranial pressure diminished CSF flow in mouse models associates pathological changes to lymphatic vessels affect their sprouting, expansion, long-term maintenance. also show affects...
Sirtuins are key players of metabolic stress response. Originally described as deacetylases, some sirtuins also exhibit poorly understood mono-adenosine 5'-diphosphate (ADP)-ribosyltransferase (mADPRT) activity. We report that the deacetylase SirT7 is a dual sirtuin, it features auto-mADPRT mADPRT occurs at previously undefined active site, and its abrogation alters chromatin distribution. identify an epigenetic pathway by which ADP-ribosyl-SirT7 recognized ADP-ribose reader mH2A1.1 under...
Transcriptional regulatory mechanisms likely contribute to the etiology of inflammatory bowel disease (IBD), as genetic variants associated with are disproportionately found at elements. However, transcription factors regulating colonic inflammation unclear. To identify these factors, we mapped epigenomic changes in epithelium upon inflammation. Epigenetic marks transcriptional elements responded dynamically and indicated a shift epithelial factor networks. Active enhancer chromatin...
Abstract Autism spectrum disorder (ASD), Tourette syndrome (TS), and attention-deficit/hyperactivity (ADHD) display strong male sex bias, due to a combination of genetic biological factors, as well selective ascertainment. While the hemizygous nature chromosome X (Chr X) in males has long been postulated key point “male vulnerability”, rare variation on this not systematically characterized large-scale whole exome sequencing studies “idiopathic” ASD, TS, ADHD. Here, we take advantage...
Abstract B lymphopoiesis is orchestrated by lineage-specific transcription factors. In cell progenitors, lineage commitment mediated Pax5, which commonly mutated in acute lymphoblastic leukemia. Despite its essential role immunity, the mechanisms regulating Pax5 function remain largely unknown. Here, we found that NAD + -dependent enzyme SIRT7 coordinates development through deacetylation of at K198, promotes protein stability and transcriptional activity. Neither K198 deacetylated nor...
Spinal cord injury (SCI) results in significant neurological deficits, with no currently available curative therapies. Neural progenitor cell (NPC) transplantation has emerged as a promising approach for neural repair, graft-derived neurons (GDNs) can integrate into the host spinal and support axon regeneration. However, mechanisms underlying functional recovery remain poorly understood. In this study, we investigate synaptic integration of NPC-derived locomotor circuits, projection patterns...
p53 is a hallmark tumor suppressor due in part to its role cell cycle progression, DNA damage repair, and cellular apoptosis; protein activity interrelates with the Sirtuin family of proteins, major regulators response metabolic, oxidative, genotoxic stress. In recent years, mammalian 7 (SIRT7) has emerged as pivotal regulator p53, fine-tuning context dependent manner. SIRT7 frequently overexpressed human cancer, yet precise tumorigenesis whether it involves regulation insufficiently...
Abstract Background Closed-loop behavior paradigms enable us to dissect the state-dependent neural circuits underlying in real-time. However, studying context-dependent locomotor perturbations has been challenging due limitations molecular tools and techniques for real-time manipulation of spinal cord circuits. New Method We developed a novel closed-loop optogenetic stimulation paradigm that utilizes DeepLabCut-Live pose estimation manipulate primary sensory afferent activity at specific...
Tactile perception relies on reliable transmission and modulation of low-threshold information as it travels from the periphery to brain. During pathological conditions, tactile stimuli can aberrantly engage nociceptive pathways leading touch pain, known mechanical allodynia. Two main drivers peripheral information, mechanoreceptors (LTMRs) postsynaptic dorsal column neurons (PSDCs), terminate in brainstem nuclei (DCN). Activity within DRG, spinal cord, DCN have all been implicated mediating...
Abstract Ongoing pain is often driven by direct activation of pain-sensing neurons and neuroimmune mediated sensitization. These heightened states alter physiology, reduce motor function, motivation to engage in normal behaviors. The complexity the state has evaded a comprehensive definition, especially nonverbal animals. Here mice, we capture physiological sensitized at different time points post-inflammation used computational tools automatically map behavioral signatures evoked...
SUMMARY To achieve smooth motor performance in a changing sensory environment, outputs must be constantly updated response to feedback. Inhibitory interneurons the spinal cord play an essential role shaping activity by gating transmission of information and setting pattern rhythm neurons. Here, we identify medial deep dorsal horn as “hot zone” convergent proprioceptive cutaneous from hindlimb, where inhibitory neurons show increased responsiveness input are preferentially recruited during...
Abstract Tourette disorder (TD) is poorly understood, despite affecting 1/160 children. A lack of animal models possessing construct, face, and predictive validity hinders progress in the field. We used CRISPR/Cas9 genome editing to generate mice with mutations orthologous human de novo variants two high-confidence genes, CELSR3 WWC1 . Mice Celsr3 Wwc1 exhibit cognitive and/or sensorimotor behavioral phenotypes consistent TD. Sensorimotor gating deficits, as measured by acoustic prepulse...