FURTHER STUDIES ON SPECIFIC TRANSPLANTATION ANTIGENS IN ROUS SARCOMA OF MICE

Mice allografted with different sarcomas, induced by the Schmidt-Ruppin variant of Rous sarcoma virus (RSV-SR), showed a resistance against subsequent isografting of 9 different Rous sarcomas. Transplantation resistance could also be induced by Rous mouse tumor cells x-irradiated with 8000 r or with cell-free tumor extracts, containing no demonstrable virus. No transplantation resistance could be demonstrated after allograft pretreatment with various polyoma tumors or non-viral tumors. Allograft pretreatment with Rous tumors induced no demonstrable resistance against isografting of polyoma tumors. Inoculation of RSV-SR or Rous chicken sarcoma suspension into adult mice gave no clear cut resistance against isografting of mouse sarcomas. Neither after allografting of Rous tumors nor after virus or chicken sarcoma inoculation into adult mice could virus-neutralizing activity be demonstrated in the sera. The results demonstrate the presence of common, specific transplantation antigen(s) in different Rous sarcomas in mice and speak against an identity between the transplantation antigen(s) and viral antigen(s)

Estimating Social and Ethnic Inequality in School Surveys: Biases from Child Misreporting and Parent Nonresponse

We study the biases that arise in estimates of social inequalities in children’s cognitive ability test scores due to (i) children’s misreporting of socio-economic origin and (ii) parents’ nonresponse. Unlike most previous studies, we are able to draw on linked register data with high reliability and almost no missingness and thereby jointly consider the impact of measurement error and nonresponse. Using data on 14-year-olds (n = 18,716) from a new survey conducted in England, Germany, the Netherlands, and Sweden (Children of Immigrants Longitudinal Survey in Four European Countries), we find that child reports on parental occupation are well aligned with parents’ reports in all countries, but reports on parental education less so. This leads to underestimation of socio-economic disparities when child reports of education are used, but not occupation. Selective nonresponse among parents turns out to be a real problem, resulting in similar underestimation. We also investigate conditional estimates of immigrant–non-immigrant disparities, which are surprisingly little affected by measurement error or nonresponse in socio-economic control variables. We conclude that school-based surveys on teenagers are well advised to include questions on parental occupation, while the costs for carrying out parental questionnaires may outweigh the gains

Damage-induced phosphorylation of Sld3 is important to block late origin firing.

Origins of replication are activated throughout the S phase of the cell cycle such that some origins fire early and others fire late to ensure that each chromosome is completely replicated in a timely fashion. However, in response to DNA damage or replication fork stalling, eukaryotic cells block activation of unfired origins. Human cells derived from patients with ataxia telangiectasia are deficient in this process due to the lack of a functional ataxia telangiectasia mutated (ATM) kinase and elicit radioresistant DNA synthesis after γ-irradiation(2). This effect is conserved in budding yeast, as yeast cells lacking the related kinase Mec1 (ATM and Rad3-related (ATR in humans)) also fail to inhibit DNA synthesis in the presence of DNA damage. This intra-S-phase checkpoint actively regulates DNA synthesis by inhibiting the firing of late replicating origins, and this inhibition requires both Mec1 and the downstream checkpoint kinase Rad53 (Chk2 in humans). However, the Rad53 substrate(s) whose phosphorylation is required to mediate this function has remained unknown. Here we show that the replication initiation protein Sld3 is phosphorylated by Rad53, and that this phosphorylation, along with phosphorylation of the Cdc7 kinase regulatory subunit Dbf4, blocks late origin firing in Saccharomyces cerevisiae. Upon exposure to DNA-damaging agents, cells expressing non-phosphorylatable alleles of SLD3 and DBF4 (SLD3-m25 and dbf4-m25, respectively) proceed through the S phase faster than wild-type cells by inappropriately firing late origins of replication. SLD3-m25 dbf4-m25 cells grow poorly in the presence of the replication inhibitor hydroxyurea and accumulate multiple Rad52 foci. Moreover, SLD3-m25 dbf4-m25 cells are delayed in recovering from transient blocks to replication and subsequently arrest at the DNA damage checkpoint. These data indicate that the intra-S-phase checkpoint functions to block late origin firing in adverse conditions to prevent genomic instability and maximize cell survival

Human-specific transcriptional regulation of CNS development genes by FOXP2.

The signalling pathways controlling both the evolution and development of language in the human brain remain unknown. So far, the transcription factor FOXP2 (forkhead box P2) is the only gene implicated in Mendelian forms of human speech and language dysfunction. It has been proposed that the amino acid composition in the human variant of FOXP2 has undergone accelerated evolution, and this two-amino-acid change occurred around the time of language emergence in humans. However, this remains controversial, and whether the acquisition of these amino acids in human FOXP2 has any functional consequence in human neurons remains untested. Here we demonstrate that these two human-specific amino acids alter FOXP2 function by conferring differential transcriptional regulation in vitro. We extend these observations in vivo to human and chimpanzee brain, and use network analysis to identify novel relationships among the differentially expressed genes. These data provide experimental support for the functional relevance of changes in FOXP2 that occur on the human lineage, highlighting specific pathways with direct consequences for human brain development and disease in the central nervous system (CNS). Because FOXP2 has an important role in speech and language in humans, the identified targets may have a critical function in the development and evolution of language circuitry in humans

Risk assessment of the herbicide clomazone in the aquatic life.

Clomazone (2-(2-chlorophenyl)methyl-4.4-dimethyl-3-isoxazolidinone) is a post emergence herbicide widely used in rice fields in Rio Grande do Sul (Brazil) with high activity against Gramineae at the recommended application rate(AR).of 700g/ha. The herbicide input into the aquatic ecosystem may occur by aerial application or water drainage. The presence of this chemical in the water may affect non-target organisms leading to impairments in the aquatic food chain. Studies were conducted in this work to evaluate the risk of Clomazone using the estimated mean affective concentration (EC50) for the microalgae Selenastrum capricornutum(96h), the duckweed Lemna valdiviana(96h) and the crustacean Daphnia similis(48h). The EC50 values were 11.2; 31.7 and 13.8 mg/l, respectively. According to the obtained data, and considering a direct input of the herbicide in a 10cm column water, the estimated maximum application rate that doesn't cause acute effects is 5.3 AR for S. capricornutum, 6.5 AR for D. similis and 15.0 AR for L. valdiviana. The estimated maximum application rate that doesn't cause chronic effects is 2.0 AR for D. similis, 1.6 AR for S. capricornutum and 4.5 AR for L. valviana