Ape1/Ref-1 Stimulates GDNF/GFR��1-mediated Downstream Signaling and Neuroblastoma Proliferation

We previously reported that glial cell line-derived neurotropic factor (GDNF) receptor α1 (GFRα1) is a direct target of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1). In the present study, we further analyzed the physiological roles of Ape1/Ref-1-induced GFRα1 expression in Neuro2a mouse neuroblastoma cells. Ape1/Ref-1 expression caused the clustering of GFRα1 immunoreactivity in lipid rafts in response to GDNF. We also found that Ret, a downstream target of GFRα1, was functionally activated by GDNF in Ape1/Ref-1-expressing cells. Moreover, GDNF promoted the proliferation of Ape1/Ref-1-expressing Neuro2a cells. Furthermore, GFRα1-specific RNA experiments demonstrated that the downregulation of GFRα1 by siRNA in Ape1/Ref-1-expressing cells impaired the ability of GDNF to phosphorylate Akt and PLCγ-1 and to stimulate cellular proliferation. These results show an association between Ape1/Ref-1 and GDNF/GFRα signaling, and suggest a potential molecular mechanism for the involvement of Ape1/Ref-1 in neuronal proliferation.     

Elimination of the interference of ascorbic acid in the amperometric detection of biomolecules in body fluid samples and the simple detection of uric acid in human serum and urine by using the powder microelectrode technique

A study of the electrochemical behaviour of ascorbic acid (AA) at the powder microelectrode revealed that exhaustive electrolysis of AA could be achieved within a narrow range of potential. As a result, the interference of AA in the amperometric detection of bioactive molecules in body fluid samples can be practically eliminated by employing the powder microelectrode technique. Elimination of the interference of AA can be further improved if the monitored biomolecules are strongly adsorbed on the surface of carbon powder. A good example of such a bioactive compound is uric acid (UA), which can be strongly adsorbed on the surface of acetylene black powder. In a mixture containing 0.8 μM–0.4 mM UA and a large excess of AA in 0.1 M phosphate buffer solution, the separation between the potentials of oxidation current peaks of UA and AA reaches 400 mV, and the height of the UA peak is linear with respect to the UA concentration. A very simple procedure for the detection of UA in human serum and urine samples has been worked out to illustrate the above-stated principle. Application of the same principle in the amperometric detection (and probably simultaneous determination) of other electroactive biomolecules also seems promising.     

Meiotic roles of Mec1, a budding yeast homolog of mammalian ATR/ATM

Budding yeast Mec1, a homolog of mammalian ATR/ATM, is an essential chromosome-based signal transduction protein. Mec1 is a key checkpoint regulator and plays a critical role in the maintenance of genome stability. Mec1 is also required for meiosis; loss of Mec1 functions leads to a number of meiotic defects including reduction in recombination, loss of inter-homolog bias, loss of crossover control, and failure in meiotic progression. Here we review currently available data on meiotic defects associated with loss of Mec1 functions and discuss the possibility that Mec1 may participate as a fundamentally positive player in coordinating and promoting basic meiotic chromosomal processes during normal meiosis.     

A case of huge sclerosing stromal tumor of the ovary weighing 10 kg in a 71-year-old postmenopausal woman

Sclerosing stromal tumor (SST) is a rare benign neoplasm of ovarian stromal origin and predominantly affects young women in the second and third decades. This tumor characteristically differentiates itself histologically and clinically from both thecomas and fibromas. We present a case of huge SST of the ovary weighing 10 kg in a 71-year-old postmenopausal woman with a brief review of the literature.     

Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) and lactation: an update.

Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are commonly used for the treatment of hypertension. ACEIs have been promoted as first-line therapy for selected patients with chronic hypertension and for the prevention of diabetic nephropathy, thus creating the potential for frequent ACEI exposure among women of childbearing age. ARBs are the most recent addition to the available options for antihypertensive agents. This review specifically focuses on the most up-to-date information regarding these newer antihypertensives with regard to lactation.     

Temporal relationship between idiopathic inflammatory myopathies and malignancies and its mortality: a nationwide population-based study

Clinical Rheumatology - To examine the temporal relationship between malignancies and idiopathic inflammatory myopathies (IIMs) and its impact on mortality. A retrospective cohort for IIM patients...