The p53 tumour suppressor is activated by numerous stressors to induce apoptosis, cell cycle arrest, or senescence. To study the biological effects of altered p53 function, we generated mice with a deletion mutation in the first six exons of the p53 gene that express a truncated RNA capable of encoding a carboxy-terminal p53 fragment. This mutation confers phenotypes consistent with activated p53 rather than inactivated p53. Mutant (p53+/m) mice exhibit enhanced resistance to spontaneous tumours compared with wild-type (p53+/+) littermates. As p53+/m mice age, they display an early onset of phenotypes associated with ageing. These include reduced longevity, osteoporosis, generalized organ atrophy and a diminished stress tolerance. A second line of transgenic mice containing a temperature-sensitive mutant allele of p53 also exhibits early ageing phenotypes. These data suggest that p53 has a role in regulating organismal ageing.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. Methods: All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. Results: The median age was 40 years (range, 20-73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required J Korean Med Sci. 2020 Apr 6;35(13):e142 https://doi.

BackgroundFrom May to July 2015, the Republic of Korea experienced the largest outbreak of Middle East respiratory syndrome (MERS) outside the Arabian Peninsula. A total of 186 patients, including 36 deaths, had been diagnosed with MERS-coronavirus (MERS-CoV) infection as of September 30th, 2015.Materials and MethodsWe obtained information of patients who were confirmed to have MERS-CoV infection. MERS-CoV infection was diagnosed using real-time reverse-transcriptase polymerase chain reaction assay.ResultsThe median age of the patients was 55 years (range, 16 to 86). A total of 55.4% of the patients had one or more coexisting medical conditions. The most common symptom was fever (95.2%). At admission, leukopenia (42.6%), thrombocytopenia (46.6%), and elevation of aspartate aminotransferase (42.7%) were observed. Pneumonia was detected in 68.3% of patients at admission and developed in 80.8% during the disease course. Antiviral agents were used for 74.7% of patients. Mechanical ventilation, extracorporeal membrane oxygenation, and convalescent serum were employed for 24.5%, 7.1%, and 3.8% of patients, respectively. Older age, presence of coexisting medical conditions including diabetes or chronic lung disease, presence of dyspnea, hypotension, and leukocytosis at admission, and the use of mechanical ventilation were revealed to be independent predictors of death.ConclusionThe clinical features of MERS-CoV infection in the Republic of Korea were similar to those of previous outbreaks in the Middle East. However, the overall mortality rate (20.4%) was lower than that in previous reports. Enhanced surveillance and active management of patients during the outbreak may have resulted in improved outcomes.

The Wip1 gene is a serine/threonine phosphatase that is induced in a p53-dependent manner by DNAdamaging agents. We show here that Wip1 message is expressed in moderate levels in all organs, but is present at very high levels in the testes, particularly in the postmeiotic round spermatid compartment of the seminiferous tubules. We have confirmed that Wip1 mRNA is induced by ionizing radiation in mouse tissues in a p53-dependent manner. To further determine the normal biological function of Wip1 in mammalian organisms, we have generated Wip1-deficient mice. Wip1 null mice are viable but show a variety of postnatal abnormalities, including variable male runting, male reproductive organ atrophy, reduced male fertility, and reduced male longevity. Mice lacking Wip1 show increased susceptibility to pathogens and diminished T-and B-cell function. Fibroblasts derived from Wip1 null embryos have decreased proliferation rates and appear to be compromised in entering mitosis. The data are consistent with an important role for Wip1 in spermatogenesis, lymphoid cell function, and cell cycle regulation.The p53 tumor suppressor protein plays a critical role in integration of signals that regulate cell growth and death in response to a variety of stressors (11,12,26). Loss or mutation of the gene encoding the p53 protein predisposes a cell to neoplastic transformation (8,21,23). Mutation of the p53 gene has been observed in half of all human cancers, and loss of p53 signaling may play a role in over 80% of all tumors (8,12,13).In response to a variety of cell stresses, including DNA damage, aberrantly activated oncogenes, and hypoxia, p53 is phosphorylated on multiple serine and threonine residues, becomes stabilized, and accumulates in the nucleus (11,12,26). The activated p53 protein is a transcription factor that can upregulate as well as downregulate a battery of genes which participate in the biological response to the cell stress. This response can be in the form of cell cycle arrest, apoptosis, differentiation, or senescence. Any of these responses are likely to prevent the outgrowth of a nascent cancer cell.Among the many p53 transcriptional targets that have recently been identified is the wild-type p53-induced phosphatase (Wip1) (5). The Wip1 gene exhibits a close similarity to type 2C phosphatases (2, 5). The type 2C phosphatases are distinguished from the PP1, PP2A, and PP2B phosphatases by their insensitivity to phosphatase inhibitors such as okadaic acid and requirement for divalent cations (Mg 2ϩ or Mn 2ϩ ) (3, 15). The type 2C phosphatases have been identified in a wide range of organisms and have often been associated with stress response, sexual differentiation, and cell cycle control (3, 15).The Wip1 gene was originally identified in a screen for p53 target genes (5). Wip1 was shown to be upregulated in a p53-dependent manner by ionizing radiation (IR) and by UV radiation (UV) (5, 25). Following IR, Wip1 mRNA was rapidly induced and the protein was localized to the nucleus. The first specific target of the W...

We evaluated the clinical characteristics, cytokine/chemokine concentrations, viral shedding and antibody kinetics in 30 patients with Middle East respiratory syndrome (MERS), including 6 non-survivors admitted to 3 MERS-designated hospitals. Old age, low albumin, altered mentality and high pneumonia severity index score at admission were risk factors for mortality. In addition, severe signs of inflammation at initial presentation (at hospital days 1-4), such as high inducible protein-10 (p=0.0013), monocyte chemoattractant protein-1 (p=0.0007) and interleukin 6 (p=0.0007) concentrations, and poor viral control (high viral load at hospital days 5-10, p<0.001) without adequate antibody titres (low antibody titre at hospital days 11-16, p=0.07) during the course of disease, were associated with mortality.

Bacterial gastroenteritis is a risk factor of IBS and the duration of diarrhea as the index of severity of initial illness is an independent risk factor of PI-IBS. The clinical course of PI-IBS is variable over the 1 year of follow-up.

This nationwide, prospective cohort study evaluated pulmonary function and radiological sequelae according to infection severity in 73 survivors from the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea. Patients with severe pneumonia in MERS-coronavirus infection had more impaired pulmonary function than those with no or mild pneumonia at the 1-year follow-up, which was compatible with the radiological sequelae. Severe pneumonia significantly impairs pulmonary function and makes long radiological sequelae in MERS.

We have fabricated Mn-doped Bi 2 Te 3 and Sb 2 Te 3 single crystals by the vertical gradient solidification method. The compositions and crystal structures of Bi 2-x Mn x Te 3 and Sb 2-x Mn x Te 3 were determined using Electron Probe Micro-Analyzer (EPMA) and powder X-ray diffraction (XRD) patterns, respectively. Both crystal structures were rhombohedral with smaller lattice constants because of the smaller atomic radius of Mn than those of Bi and Sb. Based on the magnetization measurements, Mn-doped Bi 2 Te 3 and Sb 2 Te 3 compounds have ferromagnetic ordering at T C = 10 and 17 K, respectively.