Analysis of a degron-containing reporter protein GFP-CL1 reveals a role for SUMO1 in cytosolic protein quality control.

Misfolded proteins are recognized and degraded through protein quality control (PQC) pathways, which are essential for maintaining proteostasis and normal cellular functions. Defects in PQC can result in disease, including cancer, cardiovascular disease, and neurodegeneration. The small ubiquitin-related modifiers (SUMOs) were previously implicated in the degradation of nuclear misfolded proteins, but their functions in cytoplasmic PQC are unclear.

RNF4 Regulates the BLM Helicase in Recovery From Replication Fork Collapse.

Sumoylation is an important enhancer of responses to DNA replication stress and the SUMO-targeted ubiquitin E3 ligase RNF4 regulates these responses by ubiquitylation of sumoylated DNA damage response factors. The specific targets and functional consequences of RNF4 regulation in response to replication stress, however, have not been fully characterized. Here we demonstrated that RNF4 is required for the restart of DNA replication following prolonged hydroxyurea (HU)-induced replication stress.

SUMO paralogue-specific functions revealed through systematic analysis of human knockout cell lines and gene expression data.

The small ubiquitin-related modifiers (SUMOs) regulate nearly every aspect of cellular function, from gene expression in the nucleus to ion transport at the plasma membrane. In humans, the SUMO pathway has five SUMO paralogues with sequence homologies that range from 45% to 97%. SUMO1 and SUMO2 are the most distantly related paralogues and also the best studied.

SUMOylation of mitofusins: A potential mechanism for perinuclear mitochondrial congression in cells treated with mitochondrial stressors.

Depolarized/damaged mitochondria aggregate at the perinuclear region prior to mitophagy in cells treated with mitochondrial stressors. However, the cellular mechanism(s) by which damaged mitochondria are transported and remain aggregated at the perinuclear region is unknown. Here, we demonstrate that mitofusins (Mfn1/2) are post-translationally modified by SUMO2 (Small Ubiquitin-related Modifier 2) in Human embryonic kidney 293 (Hek293) cells treated with protonophore CCCP and proteasome inhibitor MG132, both known mitochondrial stressors.

Selection of a Clinical Lead TCR Targeting Alpha-Fetoprotein-Positive Liver Cancer Based on a Balance of Risk and Benefit.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with a poor prognosis and limited therapeutic options. Alpha-fetoprotein (AFP), an established clinical biomarker of HCC, has been employed as an attractive target for T cell-based immunotherapy against this disease given its high expression in the tumor and restricted expression in normal tissues. We have identified a number of T cell receptors (TCRs) recognizing the HLA-A02:01 restricted AFP peptide FMNKFIYEI, providing a TCR candidate pool for identifying TCRs with optimal clinical benefit.

Gender and age disparity in the initiation of life-supporting treatments: a population-based cohort study.

Background: The relationships between age and the life-supporting treatments use, and between gender and the life-supporting treatments use are still controversial. Using extracorporeal membrane oxygenation as an example of life-supporting treatments, the objectives of this study were: (1) to examine the relationship between age and the extracorporeal membrane oxygenation use; (2) to examine the relationship between age and the extracorporeal membrane oxygenation use; and (3) to deliberate the ethical and societal implications of age and gender disparities in the initiation of extracorporeal membrane oxygenation.

Methods: This is a population-based, retrospective cohort study.

Severe exacerbation and pneumonia in COPD patients treated with fixed combinations of inhaled corticosteroid and long-acting beta2 agonist.

Background: It remains unclear whether severe exacerbation and pneumonia of COPD differs between patients treated with budesonide/formoterol and those treated with fluticasone/salmeterol. Therefore, we conducted a comparative study of those who used budesonide/formoterol and those treated with fluticasone/salmeterol for COPD.

Methods: Subjects in this population-based cohort study comprised patients with COPD who were treated with a fixed combination of budesonide/formoterol or fluticasone/salmeterol.

The association between inhaled corticosteroid and pneumonia in COPD patients: the improvement of patients' life quality with COPD in Taiwan (IMPACT) study.

To investigate the association between inhaled corticosteroid (ICS) exposure patterns and the risk of pneumonia in chronic obstructive pulmonary disease (COPD) patients, we performed a nested case-control study. Between 1998 and 2010, 51,739 patients, including 19,838 cases of pneumonia, were matched to 74,849 control subjects selected from a cohort of COPD patients using ICSs via risk-set sampling of the database constructed by the National Health Research Institutes of Taiwan. After adjusting for covariates, the current use of ICSs was associated with a 25% increase in the risk of pneumonia (odds ratio [OR] =1.

Short- and long-term use of medication for psychological distress after the diagnosis of cancer.

Purpose: This study investigated the short- and long-term use of medication for psychological distress after the diagnosis of cancer.

Methods: Longitudinal data from the Taiwan National Health Insurance database were used to follow 35,137 cancer patients for 2.5 years after being diagnosed in 2006 and 2007.

Haplotypes of the D-Amino Acid Oxidase Gene Are Significantly Associated with Schizophrenia and Its Neurocognitive Deficits.

D-amino acid oxidase (DAO) has been reported to be associated with schizophrenia. This study aimed to search for genetic variants associated with this gene. The genomic regions of all exons, highly conserved regions of introns, and promoters of this gene were sequenced.

Characterizing Requirements for Small Ubiquitin-like Modifier (SUMO) Modification and Binding on Base Excision Repair Activity of Thymine-DNA Glycosylase in Vivo.

Thymine-DNA glycosylase (TDG) plays critical roles in DNA base excision repair and DNA demethylation. It has been proposed, based on structural studies and in vitro biochemistry, that sumoylation is required for efficient TDG enzymatic turnover following base excision. However, whether sumoylation is required for TDG activity in vivo has not previously been tested.

ANXA7, PPP3CB, DNAJC9, and ZMYND17 genes at chromosome 10q22 associated with the subgroup of schizophrenia with deficits in attention and executive function.

Background: A genome scan of Taiwanese schizophrenia families suggested linkage to chromosome 10q22.3. We aimed to find the candidate genes in this region.

Genetic variants of IL-6 and its receptor are not associated with schizophrenia in Taiwan.

The pathophysiological process of schizophrenia is still unclear. The levels of interleukine-6 (IL-6) and its receptor, soluble IL-6R, have been reported to be elevated in the plasma and cerebrospinal fluid of schizophrenic patients. In this study, we tested the association of genetic variants of IL-6 and IL-6R with schizophrenia.

RASD2, MYH9, and CACNG2 genes at chromosome 22q12 associated with the subgroup of schizophrenia with non-deficit in sustained attention and executive function.

Background: In a previous linkage study of schizophrenia that included Taiwanese samples, the marker D22S278 (22q12.3) was significantly linked to schizophrenia (p = .001).

Association analysis of monoamine oxidase A gene and bipolar affective disorder in Han Chinese.

Background: Monoamine oxidase A (MAOA) is a mitochondrial enzyme involved in degrading several different biological amines, including serotonin. Although several pieces of evidence suggested that MAOA is important in the etiology of bipolar affective disorder (BPD), associations for markers of the MAOA gene with BPD were not conclusive and the association has not been investigated in Taiwanese population. This study was designed to illustrate the role of MAOA in the etiology of BPD in Han Chinese.

The influences of Taiwan's generic grouping price policy on drug prices and expenditures: evidence from analysing the consumption of the three most-used classes of cardiovascular drugs.

Background: Controlling the growth of pharmaceutical expenditures is a major global challenge. Promotion of generic drug prescriptions or use is gaining increased support. There are substantial contextual differences in international experiences of implementing pharmaceutical policies related to generic drugs.

The influences of Taiwan's National Health Insurance on women's choice of prenatal care facility: Investigation of differences between rural and non-rural areas.

Background: Taiwan's National Health Insurance (NHI), implemented in 1995, substantially increased the number of health care facilities that can deliver free prenatal care. Because of the increase in such facilities, it is usually assumed that women would have more choices regarding prenatal care facilities and thus experience reduction in travel cost. Nevertheless, there has been no research exploring these issues in the literature.

An investigation of the smoking behaviours of parents before, during and after the birth of their children in Taiwan.

Background: Although many studies have investigated the negative effects of parental smoking on children and Taiwan has started campaigns to promote smoke-free homes, little is known about the smoking behaviours of Taiwanese parents during the childbearing period. To help fill the gap, this study investigated Taiwanese parents' smoking behaviours before, during and after the birth of their children, particularly focusing on smoking cessation during pregnancy and relapse after childbirth.

Methods: We used data from the Survey of Health Status of Women and Children, conducted by Taiwan's National Health Research Institutes in 2000.

HTF9C gene of 22q11.21 region associates with schizophrenia having deficit-sustained attention.

Objective: A region at chromosome 22q11.21 has been reported to potentially harbor a candidate gene for schizophrenia, ZDHHC8 (zinc finger, DHHC domain containing 8; also annotated as KIAA1292) in a number of studies. This finding has been replicated in Han Chinese, but not in other ethnicity-specific studies.

No association evidence between schizophrenia and dystrobrevin-binding protein 1 (DTNBP1) in Taiwanese families.

Several linkage studies have shown significant linkage of schizophrenia to chromosome 6p region, which includes the positional candidate genes, Dystrobrevin-binding protein 1 (DTNBP1). The aim was to examine the association evidence of the candidate gene in 693 Taiwanese families with at least two affected siblings of schizophrenia. We genotyped nine SNPs of this gene with average intermarker distance of 17 kb.

A single nucleotide polymorphism fine mapping study of chromosome 1q42.1 reveals the vulnerability genes for schizophrenia, GNPAT and DISC1: Association with impairment of sustained attention.

Background: The marker D1S251 of chromosome 1q42.1 showed significant association with schizophrenia in a Taiwanese sample. We used single nucleotide polymorphism (SNP) fine mapping to search for the vulnerability genes of schizophrenia.