Mutations in the androgen receptor (AR) gene cause a range of phenotypic abnormalities of male sexual development. At one end of the spectrum are individuals with complete androgen insensitivity (complete testicular feminization) who exhibit normal breast development and female external genitalia. At the other extreme are individuals with male phenotypes that are characterized by either subtle undervirilization or infertility. Studies in a number of different laboratories have identified mutations of the AR gene in subjects with androgen resistance syndromes. Defects that interrupt the AR open-reading frame have been traced to a number of distinct types of genetic alterations, have been identified in widely separated segments of the AR gene, and are invariably associated with the phenotype of complete androgen insensitivity. By contrast, mutations that cause single amino acid substitutions within the AR are localized to the DNA-or ligand-binding domains of the receptor protein and have been associated with the full range of androgen-resistant phenotypes. Regardless of the nature of the mutation, functional studies and assays of AR abundance suggest that the phenotypic abnormalities that result from mutation of the AR are the result of the impairment of receptor function, decreases in receptor concentration, or both.

Lon protease is a multifunction protein and operates in protein quality control and stress response pathways in mitochondria. Human Lon is upregulated under oxidative and hypoxic stresses that represent the stress phenotypes of cancer. However, little literature undertakes comprehensive and detailed investigations on the tumorigenic role of Lon. Overexpression of Lon promotes cell proliferation, apoptotic resistance to stresses, and transformation. Furthermore, Lon overexpression induces the production of mitochondrial reactive oxygen species (ROS) that result from Lon-mediated upregulation of NDUFS8, a mitochondrial Fe-S protein in complex I of electron transport chain. Increased level of mitochondrial ROS promotes cell proliferation, cell survival, cell migration, and epithelial–mesenchymal transition through mitogen-activated protein kinase (MAPK) and Ras-ERK activation. Overall, the present report for the first time demonstrates the role of Lon overexpression in tumorigenesis. Lon overexpression gives an apoptotic resistance to stresses and induces mitochondrial ROS production through Complex I as signaling molecules to activate Ras and MAPK signaling, giving the survival advantages and adaptation to cancer cells. Finally, in silico and immunohistochemistry analysis showed that Lon is overexpressed specifically in various types of cancer tissue including oral cancer.

A 45-year-old woman presented with profound watery diarrhoea, abdominal cramp and vomiting, followed by dysthesiae and paraesthesiae, generalised myalgia, retro-orbital pain and generalised pruritus approximately several hours after eating the internal organs of Sphyraena barracuda. She denied a past history of medical disease, surgery, trauma, medication use, or allergy to drugs or food. Moreover, her elder sister (51 years old), brother-in-law (59 years old) and son (25 years old) also complained of similar but less severe symptoms after eating the internal organ of S barracuda 2 weeks ago. The neurological examination disclosed clear consciousness, intact cranial nerve function and well muscle strength. The neuropsychological examination of the patient did not show callosal syndrome, for example, hemialexia, unilateral agraphia, unilateral agnosia and unilateral apraxia, too. The peripheral nervous system evaluation revealed ''cold reversal'' (reverse cold as burning, tingling or unbearable heat) manifestation, mild impairment of vibration and position sensations and generalised hyporeflexia. A brain MRI, done 4 days after the date of admission, revealed the presence of hyperintensity of corpus callosum on T2-weighted and fluid attenuation inversion recovery images, and a markedly increased signal intensity on diffusion-weighted imaging (DWI) with a reduced apparent diffusion coefficient (ADC) value (0.28610 23 mm 2 /s) (fig 1A-D). Her neurological symptoms and signs recovered almost completely 1 month later, after conservative management. A follow-up brain MRI, 3 months after discharge, showed nearly complete resolution of the corpus callosum lesion (fig 1E,F). DISCUSSIONCiguatera is a marine food poisoning caused by the ingestion of fish contaminated with ciguatoxin. 1 2 Diagnosis of ciguatera poisoning remains clinical, based on history and exclusion. The pathophysiology of ciguatera intoxication is as yet still unclear. The proposed mechanism reported in previous experimental studies was to bind to and open voltage-gated sensitive Na + channels at resting membrane potential, resulting in neural hyperexcitability. Followed by continuous Na + influx, cells become swollen because water enters the cell throughout the effect to maintain the osmotic equilibrium between intra-and extracellular space. 1 3 The mechanism was proven partially by the finding of the sural nerve oedema on biopsy. 4 Although midline corpus callosum changes on MRI are not specific, vascular lesions, traumatic axonal injury, demyelination lesions, neoplastic lesions, infection, metabolic abnormalities, epilepsy, antiepileptic drugs, thiamine deficiency and alcoholism were excluded by the clinical history, physical and neurological examination and laboratory studies in our case. 5 To our knowledge, reversible DWI and ADC abnormalities in the corpus callosum after ciguatera poisoning have never been reported before. Our patient developed reversible areas of significantly restricted proton diffusion in the corpus callosum without any evidence...

The anti-anginal drug fendiline induced internal Ca2+ release and external Ca2+ entry. Because prolonged increases in [Ca2+]i may lead to cell injury and death, the long-term effect of fendiline on the function of prostate cancer cells should be investigated.

This study presents a novel topology named high voltage-gain boost DC-DC converter with tapped-inductor. The proposed topology provides a high voltage-gain and low input current ripple which are suitable for alternative power sources such as PV and fuel-cell applications. The interleaved control mode can be used to reduce input and output filtering. Moreover, the voltage stress on MOSFETs are clamped, resulting of low onresistance (R DS(ON) ) MOSFET usage to improve efficiency. Addition to providing circuit operation and analysis with symmetric control and interleaved control modes, a simulation and laboratory prototype of the proposed topology was built and inspected under 15-28 V input, 400 V/250 W output and 100 kHz switching frequency. The results showed that the proposed circuit achieved low voltage spikes on MOSFETs. Low R DS(ON) MOSFETs were used to improved efficiency. For interleaved control mode, the input current ripple and output voltage ripple were low, requiring smaller input and output filtering.