Biochemical analyses indicate that binding and cleavage specificities define the ordered processing of human Okazaki fragments by Dna2 and FEN1

In eukaryotic Okazaki fragment processing, the RNA primer is displaced into a single-stranded flap prior to removal. Evidence suggests that some flaps become long before they are cleaved, and that this cleavage involves the sequential action of two nucleases. Strand displacement characteristics of the polymerase show that a short gap precedes the flap during synthesis. Using biochemical techniques, binding and cleavage assays presented here indicate that when the flap is ∼30 nt long the nuclease Dna2 can bind with high affinity to the flap and downstream double strand and begin cleavage. When the polymerase idles or dissociates the Dna2 can reorient for additional contacts with the upstream primer region, allowing the nuclease to remain stably bound as the flap is further shortened. The DNA can then equilibrate to a double flap that can bind Dna2 and flap endonuclease (FEN1) simultaneously. When Dna2 shortens the flap even more, FEN1 can displace the Dna2 and cleave at the flap base to make a nick for ligation

Theory of Ferromagnetism in Doped Excitonic Condensates

Nesting in a semimetal can lead to an excitonic insulator state with spontaneous coherence between conduction and valence bands and a gap for charged excitations. In this paper we present a theory of the ferromagnetic state that occurs when the density of electrons in the conduction band and holes in the valence band differ. We find an unexpectedly rich doping-field phase diagram and an unusual collective excitation spectrum that includes two gapless collective modes. We predict regions of doping and external field in which phase-separated condensates of electrons and holes with parallel spins and opposing spins coexist.Comment: 5 pages, 3 postscript file

Vertical profiles of CO\u3csub\u3e2\u3c/sub\u3e above eastern Amazonia suggest a net carbon flux to the atmosphere and balanced biosphere between 2000 and 2009

From 2000 until January 2010 vertical profiles were collected above eastern Amazonia to help determine regional-scale (∼105–106 km2) fluxes of carbon cycle-related greenhouse gases. Samples were collected aboard light aircraft between the surface and 4.3 km and a column integration technique was used to determine the CO2 flux. Measured CO2 profiles were differenced from the CO2 background determined from measurements in the tropical Atlantic. The observed annual flux between the coast and measurement sites was 0.40 ± 0.27 gC m−2 d−1 (90% confidence interval using a bootstrap analysis). The wet season (January–June) mean flux was 0.44 ± 0.38 gC m−2 d−1 (positive fluxes defined as a source to the atmosphere) and the dry season mean flux was 0.35 ± 0.17 gC m−2 d−1 (July–December). The observed flux variability is high, principally in the wet season. The influence of biomass burning has been removed using co-measured CO, and revealed the presence of a significant dry season sink. The annual mean vegetation flux, after the biomass burning correction, was 0.02 ± 0.27 gC m−2 d−1, and a clear sink was observed between August and November of −0.70 ± 0.21 gC m−2 d−1 where for all of the dry season it was −0.24 ± 0.17 gC m−2 d−1

Risqué Business? Interpersonal Anxiety and Humor in the #MeToo Era

This is the author accepted manuscript. the final version is available from the American Psychological Association via the DOI in this recordInterpersonal anxiety (i.e., the fear of negative consequences from interacting with someone) may be more prominent in post-#MeToo organizations when interacting with someone of a different gender. Initial exchanges may particularly trigger this anxiety, obfuscating key organizational decisions such as hiring. Given humor’s positive, intrapersonal stress-reduction effects, we propose that humor also reduces interpersonal anxiety. In three mixed methods experiments with hiring managers, we examined the effects of applicant and evaluator gender (i.e., same-/mixed-gender dyad), positive applicant humor (i.e., a pun), and context (i.e., gender salience) in job interviews. Results showed that mixed-gender (vs. same-gender) interactions elicited more interpersonal anxiety, particularly when gender was more salient; mixed-gender interactions also predicted downstream attitudinal outcomes (e.g., social attraction and willingness to hire) and hiring decisions (e.g., selection and rejection) via interpersonal anxiety. Although humor reduced interpersonal anxiety and its consequences for female applicants, the opposite was true for male applicants when gender was salient, because it signaled some of the same expectations that initially triggered the interpersonal anxiety: the potential for harmful sexual behavior. In sum, we integrated diversity and humor theories to examine interpersonal anxiety in same- and mixed-gender interactions, then tested the extent to which humor relieved it.Swiss National Science Foundatio

Shared as well as distinct roles of EHD proteins revealed by biochemical and functional comparisons in mammalian cells and C. elegans

BACKGROUND: The four highly homologous human EHD proteins (EHD1-4) form a distinct subfamily of the Eps15 homology domain-containing protein family and are thought to regulate endocytic recycling. Certain members of this family have been studied in different cellular contexts; however, a lack of concurrent analyses of all four proteins has impeded an appreciation of their redundant versus distinct functions. RESULTS: Here, we analyzed the four EHD proteins both in mammalian cells and in a cross-species complementation assay using a C. elegans mutant lacking the EHD ortholog RME-1. We show that all human EHD proteins rescue the vacuolated intestinal phenotype of C. elegans rme-1 mutant, are simultaneously expressed in a panel of mammalian cell lines and tissues tested, and variably homo- and hetero-oligomerize and colocalize with each other and Rab11, a recycling endosome marker. Small interfering RNA (siRNA) knock-down of EHD1, 2 and 4, and expression of dominant-negative EH domain deletion mutants showed that loss of EHD1 and 3 (and to a lesser extent EHD4) but not EHD2 function retarded transferrin exit from the endocytic recycling compartment. EH domain deletion mutants of EHD1 and 3 but not 2 or 4, induced a striking perinuclear clustering of co-transfected Rab11. Knock-down analyses indicated that EHD1 and 2 regulate the exit of cargo from the recycling endosome while EHD4, similar to that reported for EHD3 (Naslavsky et al. (2006) Mol. Biol. Cell 17, 163), regulates transport from the early endosome to the recycling endosome. CONCLUSION: Altogether, our studies suggest that concurrently expressed human EHD proteins perform shared as well as discrete functions in the endocytic recycling pathway and lay a foundation for future studies to identify and characterize the molecular pathways involved

Large apparent growth increases in boreal forests inferred from tree-rings are an artefact of sampling biases

Tree rings are thought to be a powerful tool to reconstruct historical growth changes and have been widely used to assess tree responses to global warming. Demographic inferences suggest, however, that typical sampling procedures induce spurious trends in growth reconstructions. Here we use the world’s largest single tree-ring dataset (283,536 trees from 136,621 sites) from Quebec, Canada, to assess to what extent growth reconstructions based on these - and thus any similar - data might be affected by this problem. Indeed, straightforward growth rate reconstructions based on these data suggest a six-fold increase in radial growth of black spruce (Picea mariana) from ~0.5 mm yr−1 in 1800 to ~2.5 mm yr−1 in 1990. While the strong correlation (R2 = 0.98) between this increase and that of atmospheric CO2 could suggest a causal relationship, we here unambiguously demonstrate that this growth trend is an artefact of sampling biases caused by the absence of old, fast-growing trees (cf. “slow-grower survivorship bias”) and of young, slow-growing trees (cf. “big-tree selection bias”) in the dataset. At the moment, we cannot envision how to remedy the issue of incomplete representation of cohorts in existing large-scale tree-ring datasets. Thus, innovation will be needed before such datasets can be used for growth rate reconstructions

Size and frequency of natural forest disturbances and Amazon carbon balance

Forest inventory studies in the Amazon indicate a large terrestrial carbon sink. However, field plots may fail to represent forest mortality processes at landscape-scales of tropical forests. Here we characterize the frequency distribution of disturbance events in natural forests from 0.01 ha to 2,651 ha size throughout Amazonia using a novel combination of forest inventory, airborne lidar and satellite remote sensing data. We find that small-scale mortality events are responsible for aboveground biomass losses of B1.28 Pg C y 1 over the entire Amazon region. We also find that intermediate-scale disturbances account for losses of B0.01 Pg C y 1 , and that the largest-scale disturbances as a result of blow-downs only account for losses of B0.003 Pg C y 1 . Simulation of growth and mortality indicates that even when all carbon losses from intermediate and large-scale disturbances are considered, these are outweighed by the net biomass accumulation by tree growth, supporting the inference of an Amazon carbon sink

Patients' satisfaction with community treatment: a pilot cross-sectional survey adopting multiple perspectives.

ACCESSIBLE SUMMARY: Patients' satisfaction is scarcely studied within the context of community treatment for adolescents. Thus, this study adopts a multiple perspective on patients' satisfaction (including service users as well as staff members). The results highlighted that all informants (patients, foster carers in foster homes and professional caregivers from community treatment teams) perceived the patients to be satisfied, with foster carers reporting the highest patient satisfaction rate. Considering the patient satisfaction rate from multiple perspectives provides complementary understandings. Clinical outcomes and, specifically, a reduction in emotional difficulties were related to patient's satisfaction, but only from the patients' perspective. ABSTRACT: Community treatment (CT) teams in Switzerland provide care to patients who are unable to use regular child and adolescent mental health services (i.e. inpatient and outpatients facilities). No study has considered patients' self-rated satisfaction alongside with staff members' perspectives on patient satisfaction. Thus, adopting a cross-sectional survey design, we collected patients' satisfaction using the Client Satisfaction Questionnaire (CSQ-8), rated by multiple informants (patients, foster carers in foster homes and professional caregivers from CT teams). Professional caregivers assessed clinical outcomes using the Health of the Nation Outcome Scale for Children and Adolescents. The results indicated that all informants were satisfied with the community treatment teams. The satisfaction scores were not correlated across informants; however, the alleviation of emotional symptoms was correlated with patients' satisfaction. This study indicated that the use of a combined approach including the views of service users and professionals gives important complementary information. Finally, in our sample, lower emotional symptoms were linked to enhanced patient satisfaction. This study demonstrated the importance of considering multiple perspectives to obtain the most accurate picture of patients' satisfaction. Second, focusing on the reduction of emotional symptoms might lead to a higher degree of patients' satisfaction