TESTING THE BINARY TRIGGER HYPOTHESIS IN FUors

We present observations of three FU Orionis objects (hereafter, FUors) with nonredundant aperture-mask interferometry (NRM) at 1.59 um and 2.12 um that probe for binary companions on the scale of the protoplanetary disk that feeds their accretion outbursts. We do not identify any companions to V1515 Cyg or HBC 722, but we do resolve a close binary companion to V1057 Cyg that is at the diffraction limit (rho = 58.3 +/- 1.4 mas or 30 +/- 5 AU) and currently much fainter than the outbursting star (delta(K') = 3.34 +/- 0.10 mag). Given the flux excess of the outbursting star, we estimate that the mass of the companion (M ~ 0.25 Msun) is similar to or slightly below that of the FUor itself, and therefore it resembles a typical T Tauri binary system. Our observations only achieve contrast limits of delta(K') ~ 4 mag, and hence we are only sensitive to companions that were near or above the pre-outburst luminosity of the FUors. It remains plausible that FUor outbursts could be tied to the presence of a close binary companion. However, we argue from the system geometry and mass reservoir considerations that these outbursts are not directly tied to the orbital period (i.e., occurring at periastron passage), but instead must only occur infrequently.Comment: 6 pages, 2 figure

A Ctf4 trimer couples the CMG helicase to DNA polymerase α in the eukaryotic replisome

Efficient duplication of the genome requires the concerted action of helicase and DNA polymerases at replication forks(1), to avoid stalling of the replication machinery and consequent genomic instability(2-4). In eukaryotes, the physical coupling between helicase and DNA polymerases remains poorly understood. Here we define the molecular mechanism by which the yeast Ctf4 protein links the Cdc45-MCM-GINS (CMG) DNA helicase to DNA polymerase α (Pol α) within the replisome. We use X-ray crystallography and electron microscopy to show that Ctf4 self-associates in a constitutive disk-shaped trimer. Trimerization depends on a β-propeller domain in the carboxy-terminal half of the protein, which is fused to a helical extension that protrudes from one face of the trimeric disk. Critically, Pol α and the CMG helicase share a common mechanism of interaction with Ctf4. We show that the N-terminal tails of the catalytic subunit of Pol α and the Sld5 subunit of GINS contain a conserved Ctf4-binding motif that docks onto the exposed helical extension of a Ctf4 protomer within the trimer. Accordingly, we demonstrate that one Ctf4 trimer can support binding of up to three partner proteins, including the simultaneous association with both Pol α and GINS. Our findings indicate that Ctf4 can couple two molecules of Pol α to one CMG helicase within the replisome, providing a new paradigm for lagging-strand synthesis in eukaryotes that resembles the emerging model for the simpler replisome of E. coli(5-8). The ability of Ctf4 to act as a platform for multivalent interactions illustrates a mechanism for the concurrent recruitment of factors that act together at the fork

Deammonifisering av Rejekt Forbehandlet med Termisk Hydrolyse

Cambi sin termiske hydrolyse prosess(THP) er en kjent og effektiv forbehandlingsprosess for slam før den stabiliseres i en råtnetank. Vannstrømmen som resulterer etter at det fordøyde slammet er avvannet, er rik på ammonium og kalles rejekt. Deammonifisering er en energieffektiv og kjent mikrobiell nitrogenfjerningsprosess for rejekt hvor ammonium omdannes til nitrogengass via nitritt, uten behov for en tilgjengelig karbonkilde. Denne prosessen utføres av ammonium oksiderende bakterier(AOB) og anaerobe ammonium oksiderende bakterier(anammox). Rejekt fra en råtnetank med THP forbehandling har en høyere konsentrasjon av ammonium og kjemisk oksygenforbruk(KOF) sammenlignet med konvensjonelt rejekt. Deammonifisering av THP rejekt har vist seg å være mindre effektivt enn for konvensjonelt rejekt, og det spekuleres i om det er de høye KOF-konsentrasjonene som virker inhiberende på prosessen. Målet med dette arbeidet var å undersøke mulige hemmende virkninger på deammonifiseringsprosessen fra ulike KOF-fraksjoner som finnes i THP rejekt. Dette inkluderte også undersøkelser av mulig tilstedeværelse av heterotrofe organismer grunnet tilgjengeligheten av bionedbrytbart KOF. Deammonifisering av THP rejekt i IFAS ANITA Mox prosessen ble undersøkt i både simuleringer og laboratorieforsøk. Kun anammox biomassen, som vokste på K5 bærere, ble undersøkt i laboratorieforsøkene. Simuleringene viste konkurranse mellom heterotrofe organismer og AOB, konsentrasjonen av AOB i prosessen ble redusert når fraksjonene med bionedbrytbart KOF økte. Ingen tydelige observasjoner av inhibering av anammox ble observert. Laboratorieforsøkene viste tilstedeværelse av heterotrofe denitrifiserende bakterier som konkurrerte med anammox. En høyere konkurranse for nitritt ble observert for økende eksponering av THP rejekt, også for THP rejekt med reduserte KOF-konsentrasjoner. Reduksjon i de større KOF-fraksjonene i THP rejektet minket anammox aktiviteten, mens reduksjon i de mindre KOF-fraksjonene økte anammox aktiviteten. Både simuleringene og laboratorieforsøkene indikerte at de minste og bionedbrytbare KOF-forbindelsene ga en høyere vekst og konkurranse fra heterotrofe organismer, som resulterte i at ytelsen til den deammonifiserende biomassen ble svekket. Resultatene kunne verken utelukke eller konkludere med at andre forbindelser tilstede i THP rejektet virket inhiberende på prosessen

Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study

Background: Human genetic factors are important determinants of malaria risk. We investigated associations between multiple candidate polymorphisms—many related to the structure or function of red blood cells—and risk for severe Plasmodium falciparum malaria and its specific phenotypes, including cerebral malaria, severe malaria anaemia, and respiratory distress. Methods: We did a case-control study in Kilifi County, Kenya. We recruited as cases children presenting with severe malaria to the high-dependency ward of Kilifi County Hospital. We included as controls infants born in the local community between Aug 1, 2006, and Sept 30, 2010, who were part of a genetics study. We tested for associations between a range of candidate malaria-protective genes and risk for severe malaria and its specific phenotypes. We used a permutation approach to account for multiple comparisons between polymorphisms and severe malaria. We judged p values less than 0·005 significant for the primary analysis of the association between candidate genes and severe malaria. Findings: Between June 11, 1995, and June 12, 2008, 2244 children with severe malaria were recruited to the study, and 3949 infants were included as controls. Overall, 263 (12%) of 2244 children with severe malaria died in hospital, including 196 (16%) of 1233 with cerebral malaria. We investigated 121 polymorphisms in 70 candidate severe malaria-associated genes. We found significant associations between risk for severe malaria overall and polymorphisms in 15 genes or locations, of which most were related to red blood cells: ABO, ATP2B4, ARL14, CD40LG, FREM3, INPP4B, G6PD, HBA (both HBA1 and HBA2), HBB, IL10, LPHN2 (also known as ADGRL2), LOC727982, RPS6KL1, CAND1, and GNAS. Combined, these genetic associations accounted for 5·2% of the variance in risk for developing severe malaria among individuals in the general population. We confirmed established associations between severe malaria and sickle-cell trait (odds ratio [OR] 0·15, 95% CI 0·11–0·20; p=2·61 × 10−58), blood group O (0·74, 0·66–0·82; p=6·26 × 10−8), and –α3·7-thalassaemia (0·83, 0·76–0·90; p=2·06 × 10−6). We also found strong associations between overall risk of severe malaria and polymorphisms in both ATP2B4 (OR 0·76, 95% CI 0·63–0·92; p=0·001) and FREM3 (0·64, 0·53–0·79; p=3·18 × 10−14). The association with FREM3 could be accounted for by linkage disequilibrium with a complex structural mutation within the glycophorin gene region (comprising GYPA, GYPB, and GYPE) that encodes for the rare Dantu blood group antigen. Heterozygosity for Dantu was associated with risk for severe malaria (OR 0·57, 95% CI 0·49–0·68; p=3·22 × 10−11), as was homozygosity (0·26, 0·11–0·62; p=0·002). Interpretation: Both ATP2B4 and the Dantu blood group antigen are associated with the structure and function of red blood cells. ATP2B4 codes for plasma membrane calcium-transporting ATPase 4 (the major calcium pump on red blood cells) and the glycophorins are ligands for parasites to invade red blood cells. Future work should aim at uncovering the mechanisms by which these polymorphisms can result in severe malaria protection and investigate the implications of these associations for wider health. Funding: Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative