Mutations in the fused in sarcoma (FUS, also known as translated in liposarcoma) gene have been recently discovered to be associated with familial amyotrophic lateral sclerosis (FALS) in African, European and American populations. In a Japanese family with FALS, we found the R521C FUS mutation, which has been reported to be found in various ethnic backgrounds. The family history revealed 23 patients with FALS among 46 family members, suggesting a 100% penetrance rate. They developed muscle weakness at an average age of 35.3 years, followed by dysarthria, dysphagia, spasticity and muscle atrophy. The average age of death was 37.2 years. Neuropathological examination of the index case revealed remarkable atrophy of the brainstem tegmentum characterized by cytoplasmic basophilic inclusion bodies in the neurons of the brainstem. We screened 40 FALS families in Japan and found 4 mutations (S513P, K510E, R514S, H517P) in exon 14 and 15 of FUS. Even in Asian races, FALS with FUS mutations may have the common characteristics of early onset, rapid progress and high penetrance rate, although in patients with the S513P mutation it was late-onset. Degeneration in multiple systems and cytoplasmic basophilic inclusion bodies were found in the autopsied cases.Journal of Human Genetics advance online publication, 12 March 2010; doi:10.1038/jhg.2010.16.

BACKGROUND: Right ventricular (RV) dysfunction is associated with adverse outcomes in heart failure (HF). Mechanical unloading should be more effective than pharmacologic therapy to reduce RV afterload and improve RV function. We compared RV size and function after aggressive medical unloading therapy to that achieved in the same patients after 3 months of left ventricular assist device (LVAD) support. METHODS AND RESULTS: We studied 20 patients who underwent isolated LVAD placement (9 pulsatile and 11 axial flow). Echocardiograms were performed after inpatient optimization with diuretic and inotropic therapy and compared with studies done after 3 months of LVAD support. After medical optimization right atrial pressure was 11 +/- 5 mm Hg, mean pulmonary artery pressure 36 +/- 11 mm Hg, pulmonary capillary wedge pressure 23 +/- 9 mm Hg, and cardiac index 2.0 +/- 0.6 L.min.m(2). Preoperatively, RV dysfunction was moderate (2.6 +/- 0.9 on a 0 to 4 scale), RV diameter at the base was 3.1 +/- 0.6 cm, and mid-RV was 3.5 +/- 0.6 cm. After median LVAD support of 123 days (92 to 170), RV size and global RV dysfunction (2.6 +/- 0.9) failed to improve, despite reduced RV afterload. CONCLUSIONS: RV dysfunction seen on intensive medical therapy persisted after 3 months of LVAD unloading therapy. Selection of candidates for isolated LV support should anticipate persistence of RV dysfunction observed on inotropic therapy.

Angiogenesis is not only dependent on endothelial cell invasion and proliferation, it also requires pericyte coverage of vascular sprouts for stabilization of vascular walls. Clinical efficacy of angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signaling pathway is still limited to date. We hypothesized that the level of vessel maturation is critically involved in the response to antiangiogenic therapies. To test this hypothesis, we evaluated the vascular network in spontaneously developing melanomas of MT/ret transgenic mice after using PTK787/ZK222584 for anti-VEGF therapy but also analyzed human melanoma metastases taken at clinical relapse in patients undergoing adjuvant treatment using bevacizumab. Both experimental settings showed that tumor vessels, which are resistant to anti-VEGF therapy, are characterized by enhanced vessel diameter and normalization of the vascular bed by coverage of mature pericytes and immunoreactivity for desmin, NG-2, platelet-derived growth factor receptor beta, and the late-stage maturity marker alpha smooth muscle actin. Our findings emphasize that the level of mural cell differentiation and stabilization of the vascular wall significantly contribute to the response toward antiangiogenic therapy in melanoma. This study may be useful in paving the way toward a more rational development of second generation antiangiogenic combination therapies and in providing, for the first time, a murine model to study this.

BACKGROUND: Age at the first psychotic episode and an interval between the onset of epilepsy and that of psychosis reflect developmental processes of interictal psychosis. However, factors relating to these indices remain unknown. AIMS: To identify clinical variables that are associated with the timing of the development of interictal psychosis. METHOD: In 285 adults with epilepsy with interictal psychosis, effects of epileptic (epilepsy type), organic (intellectual functioning) and genetic (family history of psychosis) variables on timing of the development of psychosis were examined. RESULTS: The mean interval between the onset of epilepsy and that of psychosis was 14.4 years. Some psychosis occurred within a few years of the first seizure. Generalised epilepsy, normal intellectual function and a positive family history of psychosis were associated with early onset of psychosis. CONCLUSIONS: Early development of interictal psychosis in people with epilepsy may reflect other individual vulnerabilities to psychosis rather than epilepsy-related damage.

Primary adenocarcinoma of the urinary tract producing tumor markers is extremely rare. We report 2 cases of advanced adenocarcinoma of the urinary tract producing carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 125 (CA125), which were completely resected after induction chemotherapy with paclitaxel and carboplatin. Patient 1 was a 72-year-old woman with adenocarcinoma of the right renal pelvis and ureter. Patient 2 was a 73-year-old woman with adenocarcinoma of the bladder. Serum levels of CEA, CA19-9 and CA125 were extremely elevated in both cases. They were successfully treated with paclitaxel puls carboplatin followed by surgery. Both patients were proved to have achieved pathological complete regression by surgical specimens and have been alive without recurrence for more than 18 and 6 months, respectively.

Many of the actions of 1alpha,25-dihydroxyvitamin D(3)[1,25(OH)(2)D(3)] are mediated by binding to the nuclear vitamin D receptor (VDR). VDR is a member of a superfamily of nuclear receptors that are ligand-dependent transcription factors. Ligand binding induces conformational changes in the VDR that enable the receptor to interact with other coactivators to modulate gene transcription. In order to better characterize the binding of the VDR to 1,25(OH)(2)D(3) and to analogs of 1,25(OH)(2)D(3), we have cloned the cDNA for the human VDR into the pTwin1 expression system. The expression system results in the cDNA for a chitin-binding peptide and a yeast intein fused in frame with the N-terminal end of the cDNA for VDR. The intein cDNA codes for a self-cleaving peptide that can release VDR, without any additional amino acids, from a chitin column by changing the pH of the buffer. Western blot analysis of the VDR-fusion protein indicates that a protein of approximately 75 kDA was obtained as expected.

High quality holograms of flat objects are produced by developing an achromatic-fringe system that consists of a monochromatic but spatially incoherent source, a holographic beam splitting device, and a pair of Fourier transform lenses. The effects of using an incoherent extended source and the transfer characteristics of the holograms are discussed. Emphasis is also placed on the advantages of developing lens Fourier transform holography along with the practical lens systems. A further possible extension of the system to attain high storage density as well as high quality holograms is proposed by making use of a new type of pseudorandom phase sequence.

Ecology letters (2010) Abstract The evolutionary stability of mutualisms is enhanced when partners possess mechanisms to prevent overexploitation by one another. In obligate pollination-seed consumption mutualisms, selective abortion of flowers containing excessive eggs represents one such mechanism, but empirical tests have long been limited to the yucca-yucca moth mutualism. We present evidence for selective abortion in the recently discovered mutualism between Glochidion trees and Epicephala moths. In Glochidion acuminatum, proportion of aborted flowers progressively increased both with higher egg load and increased ovule damage. Selective abortion resulted in a 16% seed production increase compared with expectations under random abortion, and moths suffered fitness losses as high as 62% when ovipositing into pre-infested flowers. Moth eggs were laid singly more often than expected under random oviposition, thus avoiding potential disadvantages from multiple infestations. As new pollination mutualisms are being discovered, selective abortion mechanisms may prove to be more widespread than previously thought.

We found a new hydrophilic protein in Arabidopsis thaliana. Real-time PCR demonstrated that the protein was expressed in roots. Histochemical analysis of promoter-beta-glucuronidase fusions demonstrated its extensive expression in root hairs. The protein is rich in Pro, Glu, Val and Lys residues (PEVK-rich domain), and bound Ca(2+) even in the presence of Mg(2+) and K(+) when examined by the (45)Ca overlay assay. Treatment of seedlings with K(+), Mn(2+), Zn(2+), Na(+), abscisic acid, and gibberellic acid, and the cold and drought stresses enhanced the transcription. Expression of the protein linked with green fluorescent protein in A. thaliana showed its plasma membrane localization and cell-specific expression in the epidermal cells including root hairs and the elongating pollen tubes. Therefore, we named the protein PCaP2 (plasma membrane associated Ca(2+)-binding protein-2). The substitution of Gly at position 2 with Ala resulted in the cytoplasmic localization of PCaP2. These results and the N-terminal characteristic motif suggest that PCaP2 is N-myristoylated at Gly-2. We examined the binding capacity to phosphatidylinositol phosphates (PtdInsP), and found that PCaP2 interacts strongly with PtdIns(3,5)P2, PtdIns(4,5)P2 and PtdIns(3,4,5)P3 and weakly with PtdIns(3,4)P2. Furthermore, calmodulin was associated with PCaP2 in a Ca(2+)-dependent manner, and its association weakened the interaction of PCaP2 with PtdInsPs. These results indicate that PCaP2 is involved in the intracellular signaling through interaction with PtdInsPs and calmodulin in growing root hairs. PCaP2 was reported as a microtubule-associated protein18 (Plant Cell, 2007, 19:877.889). We discuss the physiological roles of PCaP2 in relation to microtubules in cells.