The VHL gene is epigenetically inactivated in pheochromocytomas and abdominal paragangliomas

Pheochromocytoma (PCC) and abdominal paraganglioma (PGL) are neuroendocrine tumors that present with clinical symptoms related to increased catecholamine levels. About a third of the cases are associated with constitutional mutations in pre-disposing genes, of which some may also be somatically mutated in sporadic cases. However, little is known about inactivating epigenetic events through promoter methylation in these very genes. Using bisulphite pyrosequencing we assessed the methylation density of 11 PCC/PGL disease genes in 96 tumors (83 PCCs and 13 PGLs) and 34 normal adrenal references. Gene expression levels were determined by quantitative RT-PCR. Both tumors and normal adrenal samples exhibited low methylation index (MetI) in the EGLN1 (PDH2), MAX, MEN1, NF1, SDHB, SDHC, SDHD, SDHAF2 (SDH5), and TMEM127 promoters, not exceeding 10% in any of the samples investigated. Aberrant RET promoter methylation was observed in two cases only. For the VHL gene we found increased MetI in tumors as compared with normal adrenals (57% vs. 27%; P < 0.001), in malignant vs. benign tumors (63% vs. 55%; P < 0.05), and in PGL vs. PCC (66% vs. 55%; P < 0.0005). Decreased expression of the VHL gene was observed in all tumors compared with normal adrenals (P < 0.001). VHL MetI and gene expressions were inversely correlated (R = −0.359, P < 0.0001). Our results show that the VHL gene promoter has increased methylation compared with normal adrenals (MetI > 50%) in approximately 75% of PCCs and PGLs investigated, highlighting the role of VHL in the development of these tumors.     

A structural analysis of M protein in coronavirus assembly and morphology

The M protein of coronavirus plays a central role in virus assembly, turning cellular membranes into workshops where virus and host factors come together to make new virus particles. We investigated how M structure and organization is related to virus shape and size using cryo-electron microscopy, tomography and statistical analysis. We present evidence that suggests M can adopt two conformations and that membrane curvature is regulated by one M conformer. Elongated M protein is associated with rigidity, clusters of spikes and a relatively narrow range of membrane curvature. In contrast, compact M protein is associated with flexibility and low spike density. Analysis of several types of virus-like particles and virions revealed that S protein, N protein and genomic RNA each help to regulate virion size and variation, presumably through interactions with M. These findings provide insight into how M protein functions to promote virus assembly.     

Antiproliferative activity of 2,3-disubstituted indoles toward apoptosis-resistant cancers cells

Many types of cancer, including glioma, melanoma, NSCLC, among others, are resistant to apoptosis induction and poorly responsive to current therapies with propaptotic agents. We describe a series of 2,3-disubstituted indoles, which display cytostatic rather than cytotoxic effects in cancer cells, and serve as a new chemical scaffold to develop anticancer agents capable of combating apoptosis-resistant cancers associated with dismal prognoses.     

Ungulate browsing shapes climate change impacts on forest biodiversity in Hungary

Climate change can result in a slow disappearance of forests dominated by less drought-tolerant native European beech (Fagus sylvatica) and oak species (Quercus spp.) and further area expansion of more drought-tolerant non-native black locust (Robinia pseudoacacia) against those species in Hungary. We assumed that the shift in plant species composition was modified by selective ungulate browsing. Thus, we investigated which woody species are selected by browsing game. We have collected data on the species composition of the understory and the browsing impact on it in five different Hungarian even-aged forests between 2003 and 2005. Based on these investigations the non-native Robinia pseudoacacia living under more favourable climatic conditions was generally preferred (Jacobs’ selectivity index: D = 0.04 ± 0.77), while the native Fagus sylvatica and Quercus spp. (Q. petraea, Q. robur), both more vulnerable to increasing aridity, were avoided (D = ?0.37 ± 0.11; ?0.79 ± 0.56; ?0.9 ± 0.16; respectively) among target tree species. However, economically less or not relevant species, e.g. elderberry (Sambucus spp.), blackberry (Rubus spp.) or common dogwood (Cornus sanguinea) were the most preferred species (D = 0.01 ± 0.71; ?0.12 ± 0.58; ?0.2 ± 0.78, respectively). Our results imply that biodiversity conservation, i.e. maintaining or establishing a multi-species understory layer, can be a good solution to reduce the additional negative game impact on native target tree species suffering from drought. Due to preference for Robinia pseudoacacia selective browsing can decelerate the penetration of this species into native forest habitats. We have to consider the herbivorous pressure of ungulates and their feeding preferences in planning our future multifunctional forests in the light of climate change impacts.     

An annotated update of the scale insect checklist of?Hungary (Hemiptera,Coccoidea)

The number of scale insect species (Hemiptera: Coccoidea) known from Hungary has increased in the last 10 years by 39 (16.6 %), to a total of 274 species belonging to 112 genera in10 families. The family Pseudococcidae is the most species rich, with 101 species in 34 genera; Diaspididae contains 59 species in 27 genera; Coccidae contains 54 species in 27 genera; and the Eriococcidae contains 33 species in 8 genera. The other 6 coccoid families each contain only a few species: Asterolecaniidae (7 species in 3 genera); Ortheziidae (7 species in 4 genera); Margarodidae sensu lato (5 species in 5 genera); Cryptococcidae (3 species in 2 genera); Kermesidae (4 species in 1genus); and Cerococcidae (1 species). Of the species in the check list, 224 were found in outdoor conditions, while 50 species occurred only in indoor conditions. This paper contains 22 species recorded for the first time in the Hungarian fauna.     

Functional diversity of phytoplankton highlights long‐term gradual regime shift in the middle section of the Danube River due to global warming,human impacts and oligotrophication

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The response to gravity is correlated with the number of statoliths in Chara rhizoids.

In contrast to higher plants, Chara rhizoids have single membrane-bound compartments that appear to function as statoliths. Rhizoids were generated by germinating zygotes of Chara in either soil water (SW) medium or artificial pond water (APW) medium. Differential-interference-contrast microscopy demonstrated that rhizoids form SW-grown plants typically contain 50 to 60 statoliths per cell, whereas rhizoids from APW-grown plants contain 5 to 10 statoliths per cell. Rhizoids from SW are more responsive to gravity than rhizoids from APW because (a) SW rhizoids were oriented to gravity during vertical growth, whereas APW rhizoids were relatively disoriented, and (b) curvature of SW rhizoids was 3 to 4 times greater throughout the time course of curvature. The growth rate of APW rhizoids was significantly greater than that of SW-grown rhizoids. This latter result suggests that APW rhizoids are not limited in their ability for gravitropic curvature by growth and that these rhizoids are impaired in the early stages of gravitropism (i.e. gravity perception). Plants grown in APW appeared to be healthy because of their growth rate and the vigorous cytoplasmic streaming observed in the rhizoids. This study is comparable to earlier studies of gravitropism in starch-deficient mutants of higher plants and provides support for the role of statoliths in gravity perception.     

Reduced Gravitropism in Hypocotyls of Starch-Deficient Mutants of Arabidopsis

Gravitropism was examined in dark- and light-grown hypocotylsof wild-type (WT), two reduced starch mutants (ACG 20 and ACG27), and a starchless mutant (ACG 21) of Arabidopsis. In addition,the starch content of these four strains was studied with lightand electron microscopy. Based on time course of curvature andorientation studies, the graviresponse in hypocotyls is proportionalto the amount of starch in a genotype. Furthermore, starch mutationsseem to primarily affect gravitropism rather than differentialgrowth since both phototropic curvature and growth rates amongthe four genotypes are approximately equal. Our results suggestthat gravity perception may require a greater plastid mass inhypocotyls compared to roots. The kinetics of gravitropic curvaturealso was compared following reorientation at 45°, 90°,and 135°. As has been reported for other plant species,the optimal angle of reorientation is 135° for WT Arabidopsisand the two reduced starch mutants, but the magnitude of curvatureof the starchless mutant appears to be independent of the initialangle of displacement. Taken together, the results of the presentstudy and our previous experiments with roots of the same fourgenotypes [Kiss et al. (1996) Physiol. Plant. 97: 237] supporta plastid-based hypothesis for gravity perception in plants. (Received December 16, 1996; Accepted February 7, 1997)