Provenance of Lower Cambrian rocks in Northern Spain – U-Pb isotope ages on detrital zircons in different lithofacies

The Herrería Formation with a Lower Cambrian depositional age exposed in the Cantabrian Mountains of northern Spain is the focus of this study. The motivation of this study is related to recognized significant provenance changes between the base of the formation and the top, which would have allowed fundamentally different provenance interpretations (Zimmermann, et al., 2015). Therefore, this study concentrates on a similar lithotype (quartz-arenites), which show a variety of differing sedimentary structures pointing to different sedimentary processes including sorting. The quartz-arenites are intercalated with shales devoid of carbonate material. The recognition of acritarchs pinpoints a marine depositional environment. The youngest detrital zircon age of the Herreria Formation is 524 ± 3Ma (Zimmermann, et al., 2015). Total of four samples were collected and to identify the differences and similarities of the provenance signals of these clastic sedimentary rocks, we apply optical petrography and whole-rock geochemistry, detrital zircon age. The results indicate that: All four lithotypes point to different possible maximum depositional age ranging from 549 Ma to 581 Ma with 32 Ma in difference and even more when comparing to the previous study (Zimmermann, et al., 2015). Although the rocks are supposed to be deposited in the same tectonic event, all samples fail to provide any younger depositional age than around 560 Ma. The detrital zircon population seem to differ between arenites and quartz-arenites where the latter see to reflect a more complete population. Therefore, studies with detrital zircon populations should be treated with great caution before being interpreted in stratigraphic context. Even with the large variety of different lithofacies sampled in this study it could not reflect the real Paleozoic depositional age, with an error of about 10 %. For the maximum depositional age determination, the base of the Herrería Formation would be the most ideal one studied, but not when trying to gain the entire provenance. I would argue for only using detrital zircon data with a detailed sedimentological background in addition to a known geological substructure

CDK-Dependent Hsp70 Phosphorylation Controls G1 Cyclin Abundance and Cell-Cycle Progression

In budding yeast, the essential functions of Hsp70 chaperones Ssa1–4 are regulated through expression level, isoform specificity, and cochaperone activity. Suggesting a novel regulatory paradigm, we find that phosphorylation of Ssa1 T36 within a cyclin-dependent kinase (CDK) consensus site conserved among Hsp70 proteins alters cochaperone and client interactions. T36 phosphorylation triggers displacement of Ydj1, allowing Ssa1 to bind the G1 cyclin Cln3 and promote its degradation. The stress CDK Pho85 phosphorylates T36 upon nitrogen starvation or pheromone stimulation, destabilizing Cln3 to delay onset of S phase. In turn, the mitotic CDK Cdk1 phosphorylates T36 to block Cln3 accumulation in G2/M. Suggesting broad conservation from yeast to human, CDK-dependent phosphorylation of Hsc70 T38 similarly regulates Cyclin D1 binding and stability. These results establish an active role for Hsp70 chaperones as signal transducers mediating growth control of G1 cyclin abundance and activity

CDK-dependent Hsp70 phosphorylation controls G1 cyclin abundance and cell-cycle progression

In budding yeast, the essential functions of Hsp70 chaperones Ssa1-4 are regulated through expression level, isoform specificity, and cochaperone activity. Suggesting a novel regulatory paradigm, we find that phosphorylation of Ssa1 T36 within a cyclin-dependent kinase (CDK) consensus site conserved among Hsp70 proteins alters cochaperone and client interactions. T36 phosphorylation triggers displacement of Ydj1, allowing Ssa1 to bind the G1 cyclin Cln3 and promote its degradation. The stress CDK Pho85 phosphorylates T36 upon nitrogen starvation or pheromone stimulation, destabilizing Cln3 to delay onset of S phase. In turn, the mitotic CDK Cdk1 phosphorylates T36 to block Cln3 accumulation in G2/M. Suggesting broad conservation from yeast to human, CDK-dependent phosphorylation of Hsc70 T38 similarly regulates Cyclin D1 binding and stability. These results establish an active role for Hsp70 chaperones as signal transducers mediating growth control of G1 cyclin abundance and activity

Effectiveness of an Interprofessional Education Event for Graduate Health Professional Students

ABSTRACT Purpose: The purpose of this study was to investigate the impact of a single, optional, half-day, interprofessional education (IPE) event for a myriad of graduate-level health professional students (n=44) at a university in Illinois, USA. Methods: The researchers in this study examined students’ performance on two out of six of the domains on the Interprofessiomnal Collaborator Assessment Rubric (ICAR): Roles and Responsibilities and Communication Strategies. This study also investigated quantitative and qualitative findings related to student perceptions regarding this IPE opportunity. Results: Results indicated that students met or exceeded the minimum competency for the ranking of “developing” for all 6 of the behaviors evaluated. Results also revealed that this half-day extracurricuricular IPE event was viewed favorably by health-professional students and created a venue whereby students belonging to different health professional programs can enter into discussions and learn about each others’ respective roles and responsibilities in patient care. Conclusion: The creation and implementation of short term extracurricular IPE events may be a valuable alternative for healthcare programs that are unable to implement IPE activities due to some of the common barriers impacting the development, implementation, or continuation of IPE opportunities

Differential Growth of Francisella tularensis, Which Alters Expression of Virulence Factors, Dominant Antigens, and Surface-Carbohydrate Synthases, Governs the Apparent Virulence of Ft SchuS4 to Immunized Animals

The gram-negative bacterium Francisella tularensis (Ft) is both a potential biological weapon and a naturally occurring microbe that survives in arthropods, fresh water amoeba, and mammals with distinct phenotypes in various environments. Previously, we used a number of measurements to characterize Ft grown in Brain-Heart Infusion (BHI) broth as (1) more similar to infection-derived bacteria, and (2) slightly more virulent in naïve animals, compared to Ft grown in Mueller Hinton Broth (MHB). In these studies we observed that the free amino acids in MHB repress expression of select Ft virulence factors by an unknown mechanism. Here, we tested the hypotheses that Ft grown in BHI (BHI-Ft) accurately displays a full protein composition more similar to that reported for infection-derived Ft and that this similarity would make BHI-Ft more susceptible to pre-existing, vaccine-induced immunity than MHB-Ft. We performed comprehensive proteomic analysis of Ft grown in MHB, BHI, and BHI supplemented with casamino acids (BCA) and compared our findings to published “omics” data derived from Ft grown in vivo. Based on the abundance of ~1,000 proteins, the fingerprint of BHI-Ft is one of nutrient-deprived bacteria that—through induction of a stringent-starvation-like response—have induced the FevR regulon for expression of the bacterium's virulence factors, immuno-dominant antigens, and surface-carbohydrate synthases. To test the notion that increased abundance of dominant antigens expressed by BHI-Ft would render these bacteria more susceptible to pre-existing, vaccine-induced immunity, we employed a battery of LVS-vaccination and S4-challenge protocols using MHB- and BHI-grown Ft S4. Contrary to our hypothesis, these experiments reveal that LVS-immunization provides a barrier to infection that is significantly more effective against an MHB-S4 challenge than a BHI-S4 challenge. The differences in apparent virulence to immunized mice are profoundly greater than those observed with primary infection of naïve mice. Our findings suggest that tularemia vaccination studies should be critically evaluated in regard to the growth conditions of the challenge agent

The quantitative changes in the yeast Hsp70 and Hsp90 interactomes upon DNA damage

The molecular chaperones Hsp70 and Hsp90 participate in many important cellular processes, including how cells respond to DNA damage. Here we show the results of applied quantitative affinity-purification mass spectrometry (AP-MS) proteomics to understand the protein network through which Hsp70 and Hsp90 exert their effects on the DNA damage response (DDR). We characterized the interactomes of the yeast Hsp70 isoform Ssa1 and Hsp90 isoform Hsp82 before and after exposure to methyl methanesulfonate. We identified 256 chaperone interactors, 146 of which are novel. Although the majority of chaperone interaction remained constant under DNA damage, 5 proteins (Coq5, Ast1, Cys3, Ydr210c and Rnr4) increased in interaction with Ssa1 and/or Hsp82. This data presented here are related to [1] (Truman et al., in press). The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository (Vizcaino et al. (2013) [2]) with the dataset identifier PXD001284

CDK-Dependent Hsp70 Phosphorylation Controls G1 Cyclin Abundance and Cell-Cycle Progression

In budding yeast, the essential functions of Hsp70 chaperones Ssa1–4 are regulated through expression level, isoform specificity, and cochaperone activity. Suggesting a novel regulatory paradigm, we find that phosphorylation of Ssa1 T36 within a cyclin-dependent kinase (CDK) consensus site conserved among Hsp70 proteins alters cochaperone and client interactions. T36 phosphorylation triggers displacement of Ydj1, allowing Ssa1 to bind the G1 cyclin Cln3 and promote its degradation. The stress CDK Pho85 phosphorylates T36 upon nitrogen starvation or pheromone stimulation, destabilizing Cln3 to delay onset of S phase. In turn, the mitotic CDK Cdk1 phosphorylates T36 to block Cln3 accumulation in G2/M. Suggesting broad conservation from yeast to human, CDK-dependent phosphorylation of Hsc70 T38 similarly regulates Cyclin D1 binding and stability. These results establish an active role for Hsp70 chaperones as signal transducers mediating growth control of G1 cyclin abundance and activity