The Mutation in Chd7 Causes Misexpression of Bmp4 and Developmental Defects in Telencephalic Midline
26
Citation
68
Reference
10
Related Paper
Citation Trend
Infectivity
Cite
Citations (38)
In a soil bioassay, adult Deroceras reticulatum (Stylommatophora: Limacidae) and three different weight-classes of young Arion lusitanicus (Stylommatophora: Arionidae) were exposed to a single dosage (170 dauer larvae per g of soil) of the nematode Phasmarhabditis hermaphrodita monoxenically associated with the bacterium Moraxella osloensis. Groups of 10 slugs were continuously exposed to nematodes for 4 days, and then transferred individually to Petri-dishes containing a disc of Chinese cabbage as food. Food consumption—measured by image analysis—and slug mortality were recorded daily for 10 days. Food consumption was inhibited in both slug species tested. D. reticulatum stopped feeding 6 days after the start of nematode treatment, while all A. lusitanicus continued to feed. However, in the three weight-classes of A. lusitanicus (0.15 g, 0.24 g, 0.45 g), food consumption was reduced by at least 50 %. The greatest reduction in feeding, nearly 90 %, was noted in the smallest A. lusitanicus. The nematodes successfully killed D. reticulatum but were less efficient at killing young A. lusitanicus. At the end of the experiment, mortality was highest in D. reticultatum (98 %) and the smallest weight-class of A. lusitanicus (47 %). There was almost no mortality in the largest weight-class of A. lusitanicus treated with nematodes. P. hermaphrodita associated with M. osloensis can thus be considered as a biological control agent for young stages of A. lusitanicus for its effect as a feeding inhibitor, rather than for its ability to kill the slugs.
Slug
Cite
Citations (41)
Meiosis is critical for sexual reproduction. During meiosis, the dynamics and integrity of homologous chromosomes are tightly regulated. The genetic and molecular mechanisms governing these processes in vivo, however, remain largely unknown. In this study, we demonstrate that Bat3/Scythe is essential for survival and maintenance of male germ cells (GCs). Targeted inactivation of Bat3/Scythe in mice results in widespread apoptosis of meiotic male GCs and complete male infertility. Pachytene spermatocytes exhibit abnormal assembly and disassembly of synaptonemal complexes as demonstrated by abnormal SYCP3 staining and sustained γ-H2AX and Rad51/replication protein A foci. Further investigation revealed that a testis-specific protein, Hsp70-2/HspA2, is absent in Bat3-deficient male GCs at any stage of spermatogenesis; however, Hsp70-2 transcripts are expressed at normal levels. We found that Bat3 deficiency induces polyubiquitylation and subsequent degradation of Hsp70-2. Inhibition of proteasomal degradation restores Hsp70-2 protein levels. Our findings identify Bat3 as a critical regulator of Hsp70-2 in spermatogenesis, thereby providing a possible molecular target in idiopathic male infertility.
Degradation
Cite
Citations (51)
In response to DNA damage, p53 undergoes post-translational modifications (including acetylation) that are critical for its transcriptional activity. However, the mechanism by which p53 acetylation is regulated is still unclear. Here, we describe an essential role for HLA-B-associated transcript 3 (Bat3)/Scythe in controlling the acetylation of p53 required for DNA damage responses. Depletion of Bat3 from human and mouse cells markedly impairs p53-mediated transactivation of its target genes Puma and p21 . Although DNA damage-induced phosphorylation, stabilization, and nuclear accumulation of p53 are not significantly affected by Bat3 depletion, p53 acetylation is almost completely abolished. Bat3 forms a complex with p300, and an increased amount of Bat3 enhances the recruitment of p53 to p300 and facilitates subsequent p53 acetylation. In contrast, Bat3-depleted cells show reduced p53–p300 complex formation and decreased p53 acetylation. Furthermore, consistent with our in vitro findings, thymocytes from Bat3-deficient mice exhibit reduced induction of puma and p21, and are resistant to DNA damage-induced apoptosis in vivo. Our data indicate that Bat3 is a novel and essential regulator of p53-mediated responses to genotoxic stress, and that Bat3 controls DNA damage-induced acetylation of p53.
Cite
Citations (125)
Cite
Citations (5)
A compensatory mutation occurs when the fitness loss caused by one mutation is remedied by its epistatic interaction with a second mutation at a different site in the genome. This poorly understood biological phenomenon has important implications, not only for the evolutionary consequences of mutation, but also for the genetic complexity of adaptation. We have carried out the first direct experimental measurement of the average rate of compensatory mutation. An arbitrary selection of 21 missense substitutions with deleterious effects on fitness was introduced by site-directed mutagenesis into the bacteriophage phiX174. For each deleterious mutation, we evolved 8-16 replicate populations to determine the frequency at which a compensatory mutation, instead of the back mutation, was acquired to recover fitness. The overall frequency of compensatory mutation was approximately 70%. Deleterious mutations that were more severe were significantly more likely to be compensated for. Furthermore, experimental reversion of deleterious mutations revealed that compensatory mutations have deleterious effects in a wild-type background. A large diversity of intragenic compensatory mutations was identified from sequencing fitness-recovering genotypes. Subsequent analyses of intragenic mutation diversity revealed a significant degree of clustering around the deleterious mutation in the linear sequence and also within folded protein structures. Moreover, a likelihood analysis of mutation diversity predicts that, on average, a deleterious mutation can be compensated by about nine different intragenic compensatory mutations. We estimate that about half of all compensatory mutations are located extragenically in this organism.
Mutation Accumulation
Reversion
Epistasis
Mutation frequency
Suppressor mutation
Cite
Citations (140)
Holcus lanatus
Cite
Citations (21)
SUMMARY A hitherto unrecorded virus having flexible rod‐shaped particles about 740–760 × 13 nm was isolated from Anthoxanthum odoratwn L. It was transmitted by sap inoculation, but not by several species of insect, seed or soil to 18 species of Gramineae including wheat, oats and barley. In susceptible species the virus normally produced a mosaic mottling of the leaves which was sometimes followed by a necrotic streaking or striping.
Mosaic virus
Cite
Citations (6)
HLA-B-associated transcript 3 (BAT3) was originally identified as one of the genes located within human major histocompatibility complex. It encodes a large proline-rich protein with unknown function. In this study, we found that a fragment of the BAT3 gene product interacts with a candidate tumor suppressor, DAN, in the yeast-based two-hybrid system. We cloned the full-length rat BAT3 cDNA from a fibroblast 3Y1 cDNA library. Our sequence analysis has demonstrated that rat BAT3 cDNA is 3617 nucleotides in length and encodes a full-length BAT3 (1098 amino acids) with an estimated molecular mass of 114,801 daltons, which displays an 87.4% identity with human BAT3. The deletion experiment revealed that the N-terminal region (amino acid residues 1-80) of DAN was required for the interaction with BAT3. Green fluorescent protein-tagged BAT3 was largely localized in the cytoplasm of COS cells. Northern hybridization showed that BAT3 mRNA was expressed in all the adult rat tissues examined but predominantly in testis. In addition, the level of BAT3 mRNA expression was more downregulated in some of the transformed cells, including v-mos- and v-Ha-ras-transformed 3Y1 cells, than in the parental cells.
Cite
Citations (21)
Nonsynonymous substitution
Pseudogene
Synonymous substitution
Silent mutation
Nonsense mutation
Neutral mutation
Cite
Citations (370)