The level of origin firing inversely affects the rate of replication fork progression

DNA damage slows DNA synthesis at replication forks; however, the mechanisms remain unclear. Cdc7 kinase is required for replication origin activation, is a target of the intra-S checkpoint, and is implicated in the response to replication fork stress. Remarkably, we found that replication forks proceed more rapidly in cells lacking Cdc7 function than in wild-type cells. We traced this effect to reduced origin firing, which results in fewer replication forks and a consequent decrease in Rad53 checkpoint signaling. Depletion of Orc1, which acts in origin firing differently than Cdc7, had similar effects as Cdc7 depletion, consistent with decreased origin firing being the source of these defects. In contrast, mec1-100 cells, which initiate excess origins and also are deficient in checkpoint activation, showed slower fork progression, suggesting the number of active forks influences their rate, perhaps as a result of competition for limiting factors

International consensus statement on allergy and rhinology: Allergic rhinitis – 2023

Background: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document. Methods: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. Results: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. Conclusion: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment

†Kenyaichthyidae fam. nov and †Kenyaichthys gen. nov - First Record of a Fossil Aplocheiloid Killifish (Teleostei, Cyprinodontiformes)

The extant Cyprinodontiformes (killifishes) with their two suborders Cyprinodontoidei and Aplocheiloidei represent a diverse and well-studied group of fishes. However, their fossil record is comparatively sparse and has so far yielded members of the Cyprinodontoidei only. Here we report on cyprinodontiform fossils from the upper Miocene Lukeino Formation in the Tugen Hills of the Central Rift Valley of Kenya, which represent the first fossil record of an aplocheiloid killifish. A total of 169 specimens - mostly extraordinarily well preserved and a sample of ten extant cyprinodontiform species were studied on the basis of morphometrics, meristics and osteology. A phylogenetic analysis using PAUP was also conducted for the fossils. Both the osteological data and the phylogenetic analysis provide strong evidence for the assignment of the fossils to the Aplocheiloidei, and justify the definition of the new family dagger Kenyaichthyidae, the new genus dagger Kenyaichthys and the new species dagger K. kipkechi sp. nov. The phylogenetic analysis unexpectedly places dagger Kenyaichthys gen. nov. in a sister relationship to the Rivulidae (a purely Neotropical group),a probable explanation might be lack of available synapomorphies for the Rivulidae, Nothobranchiidae and Aplocheilidae. The specimens of dagger K. kipkechi sp. nov. show several polymorphic characters and large overlap in meristic traits, which justifies their interpretation as a species flock in statu nascendi. Patterns of variation in neural and haemal spine dimensions in the caudal vertebrae of dagger Kenyaichthys gen. nov. and the extant species studied indicate that some previously suggested synapomorphies of the Cyprinodontoidei and Aplocheiloidei need to be revised

Leveraging research infrastructure co-location to evaluate constraints on terrestrial carbon cycling in northern European forests

Integrated long-term, in-situ observations are needed to document ongoing environmental change, to “ground-truth” remote sensing and model outputs and to predict future Earth system behaviour. The scientific and societal value of in-situ observations increases with site representativeness, temporal duration, number of parameters measured and comparability within and across sites. Research Infrastructures (RIs) can support harmonised, cross-site data collection, curation and publication. Integrating RI networks through site co-location and standardised observation methods can help answers three questions about the terrestrial carbon sink: (i) What are present and future carbon sequestration rates in northern European forests? (ii) How are these rates controlled? (iii) Why do the observed patterns exist? Here, we present a conceptual model for RI co-location and highlight potential insights into the terrestrial carbon sink achievable when long-term in-situ Earth observation sites participate in multiple RI networks (e.g., ICOS and eLTER). Finally, we offer recommendations to promote RI co-location

Incised valley paleoenvironments interpreted by seismic stratigraphic approach in Patos Lagoon, Southern Brazil

<div><p>ABSTRACT: The Rio Grande do Sul (RS) coastal plain area (33,000 km 2 ) had its physiography modified several times through the Quaternary, responding to allogenic and autogenic forcings. The Patos Lagoon covers a significant area of RS coastal plain (10,000 km 2 ), where incised valleys were identified in previous works. About 1,000 km of high resolution (3.5 kHz) seismic profiles, radiocarbon datings, Standard Penetration Test (SPT) and gravity cores were analyzed to interpret the paleoenvironmental evolution as preserved in incised valley infills. Seismic facies were recognized by seismic parameters. The sediment cores were used to ground-truth the seismic interpretations and help in the paleoenvironmental identification. Key surfaces were established to detail the stratigraphical framework, and seismic facies were grouped into four seismic units, which one classified in respective system tracts within three depositional sequences. The oldest preserved deposits are predominantly fluvial and estuarine facies, representing the falling stage and lowstand system tracts. The Holocene transgressive records are dominated by muddy material, mainly represented by estuarine facies with local variations. The transgression culminated in Late Holocene deposits of Patos Lagoon, representing the highstand system tract. The depositional pattern of the vertical succession was controlled by eustatic variations, while the autogenic forcing (paleogeography and sediment supply) modulated the local facies variation.</p></div