N-Methyladenosine Demethylase FTO Contributes to Neuropathic Pain by Stabilizing G9a Expression in Primary Sensory Neurons.

Nerve injury-induced change in gene expression in primary sensory neurons of dorsal root ganglion (DRG) is critical for neuropathic pain genesis. N-methyladenosine (mA) modification of RNA represents an additional layer of gene regulation. Here, it is reported that peripheral nerve injury increases the expression of the mA demethylase fat-mass and obesity-associated proteins (FTO) in the injured DRG via the activation of Runx1, a transcription factor that binds to the gene promoter.

[Genetic study of a Chinese pedigree affected with pachyonychia congenita].

Objective: To explore the genetic basis for a Chinese pedigree affected with pachyonychia congenita (PC).

Methods: With informed consent obtained, peripheral blood samples were taken from the pedigree. Genomic DNA was extracted with a phenol/chloroform method.

Do cerebral and somatic tissue oxygen saturation measurements correlate with each other during surgery?

Intraoperative maintenance of optimal tissue oxygenation is critical; however, it is uncertain whether measurements of different tissue beds correlate with each other. Cerebral tissue oxygen saturation (SctO) measured on the forehead and somatic tissue oxygen saturation (SstO) measured on limbs, using a tissue near-infrared spectroscopy, were simultaneously recorded every 2 s in patients having spine surgery or robotic hysterectomy. Simple linear regression was used to determine the static correlation between SctO and SstO using the median values of each min for each patient.

Intraoperative physiological ranges associated with improved outcomes after major spine surgery: an observational study.

Objective: There is inadequate information about the values of many intraoperative physiological measurements that are associated with improved outcomes after surgery. The purpose of this observational study is to investigate the optimal physiological ranges during major spine surgery.

Setting: A teaching hospital in the USA.

Genotypic and phenotypic characterization of Chinese patients with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a rare hereditary skeletal dysplasia, characterized by recurrent fractures and bone deformity. This study presents a clinical characterization and mutation analysis of 668 patients, aiming to establish the mutation spectrum and to elucidate genotype-phenotype correlations in Chinese OI patients. We identified 274 sequence variants (230 in type I collagen encoding genes and 44 in noncollagen genes), including 102 novel variants, in 340 probands with a detection rate of 90%.

Disrupting interaction of PSD-95 with nNOS attenuates hemorrhage-induced thalamic pain.

Hemorrhages occurring within the thalamus lead to a pain syndrome. Clinical treatment of thalamic pain is ineffective, at least in part, due to the elusive mechanisms that underlie the induction and maintenance of thalamic pain. The present study investigated the possible contribution of a protein-protein interaction between postsynaptic density protein 95 (PSD-95) and neuronal nitric oxide synthase (nNOS) to thalamic pain in mice.

A dynamic interplay of enhancer elements regulates expression in naïve pluripotency.

Transcription factor (TF)-directed enhanceosome assembly constitutes a fundamental regulatory mechanism driving spatiotemporal gene expression programs during animal development. Despite decades of study, we know little about the dynamics or order of events animating TF assembly at -regulatory elements in living cells and the long-range molecular "dialog" between enhancers and promoters. Here, combining genetic, genomic, and imaging approaches, we characterize a complex long-range enhancer cluster governing () expression in naïve pluripotency.

G9a participates in nerve injury-induced Kcna2 downregulation in primary sensory neurons.

Nerve injury-induced downregulation of voltage-gated potassium channel subunit Kcna2 in the dorsal root ganglion (DRG) is critical for DRG neuronal excitability and neuropathic pain genesis. However, how nerve injury causes this downregulation is still elusive. Euchromatic histone-lysine N-methyltransferase 2, also known as G9a, methylates histone H3 on lysine residue 9 to predominantly produce a dynamic histone dimethylation, resulting in condensed chromatin and gene transcriptional repression.

Resetting Human Naïve Pluripotency.

The rodent naive pluripotent state is believed to represent the preimplantation inner cell mass state of the developing blastocyst and can derive self-renewing pluripotent embryonic stem cells (ESCs) in vitro. Nevertheless, human ESCs exhibit epigenetic, metabolic, and transcriptomic characteristics more akin to primed pluripotent stem cells (PSCs) derived from the postimplantation epiblast. Understanding the genetic and epigenetic mechanisms that constrain human ESCs in the primed state is crucial for the human naive pluripotent state resetting and numerous applications in regenerative medicine.

[Analysis of gross deletions of COL1A1/2 genes in Chinese families affected with osteogenesis imperfecta].

Objective: To identify deletion of large fragment in COL1A1/2 genes among patients with osteogenesis imperfecta (OI).

Methods: Genomic DNA was extracted from peripheral blood samples by a standard SDS-proteinase K-phenol/chloroform method. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect gross deletions of the COL1A1/2 genes among 46 patients affected with OI, in whom no mutation was detected in the sequences of the COL1A1/2 genes.

[Spectrum of COL1A1/2 mutations and gene diagnosis in Chinese patients with osteogenesis imperfecta].

Objective: To identify mutations of the type I collagen genes (COL1A1 and COL1A2) in the affected with osteogenesis imperfecta (OI), to establish the spectrum of COL1A1/2 mutations in Chinese OI patients, and to provide prenatal gene diagnosis to the fetuses at high risk.

Methods: Genomic DNA was extracted from peripheral blood by the standard SDS-proteinase K-phenol/chloroform method. All the coding regions and exon/intron boundaries of COL1A1/2 were screened in 200 OI cases by conventional Sanger sequencing and targeted next-generation sequencing (NGS) on Ion Torrent-personalized genome sequencing operation (Ion PGM™).

Initial clinical experience with near-infrared spectroscopy in assessing cerebral tissue oxygen saturation in cerebral vasospasm before and after intra-arterial verapamil injection.

Cerebral vasospasm is a devastating complication after subarachnoid hemorrhage. The use of cerebral tissue oxygen saturation (SctO2) to non-invasively assess changes in cerebral tissue perfusion induced by intra-arterial (IA) verapamil treatment has not been described to our knowledge. A total of 21 consecutive post-craniotomy patients scheduled for possible IA verapamil treatment of cerebral vasospasm were recruited.

Developing Defined and Scalable 3D Culture Systems for Culturing Human Pluripotent Stem Cells at High Densities.

Human pluripotent stem cells (hPSCs) - including embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) - are very promising candidates for cell therapies, tissue engineering, high throughput pharmacology screens, and toxicity testing. These applications require large numbers of high quality cells; however, scalable production of human pluripotent stem cells and their derivatives at a high density and under well-defined conditions has been a challenge. We recently reported a simple, efficient, fully defined, scalable, and good manufacturing practice (GMP) compatible 3D culture system based on a thermoreversible hydrogel for hPSC expansion and differentiation.

[Detection of pathogenic mutations in Marfan syndrome by targeted next-generation semiconductor sequencing].

Objective: To detect pathogenic mutations in Marfan syndrome (MFS) using an Ion Torrent Personal Genome Machine (PGM) and to validate the result of targeted next-generation semiconductor sequencing for the diagnosis of genetic disorders.

Methods: Peripheral blood samples were collected from three MFS patients and a normal control with informed consent. Genomic DNA was isolated by standard method and then subjected to targeted sequencing using an Ion Ampliseq(TM) Inherited Disease Panel.