Transcriptional regulation of protein complexes in yeast

BACKGROUND: Multiprotein complexes play an essential role in many cellular processes. But our knowledge of the mechanism of their formation, regulation and lifetimes is very limited. We investigated transcriptional regulation of protein complexes in yeast using two approaches. First, known regulons, manually curated or identified by genome-wide screens, were mapped onto the components of multiprotein complexes. The complexes comprised manually curated ones and those characterized by high-throughput analyses. Second, putative regulatory sequence motifs were identified in the upstream regions of the genes involved in individual complexes and regulons were predicted on the basis of these motifs. RESULTS: Only a very small fraction of the analyzed complexes (5-6%) have subsets of their components mapping onto known regulons. Likewise, regulatory motifs are detected in only about 8-15% of the complexes, and in those, about half of the components are on average part of predicted regulons. In the manually curated complexes, the so-called 'permanent' assemblies have a larger fraction of their components belonging to putative regulons than 'transient' complexes. For the noisier set of complexes identified by high-throughput screens, valuable insights are obtained into the function and regulation of individual genes. CONCLUSIONS: A small fraction of the known multiprotein complexes in yeast seems to have at least a subset of their components co-regulated on the transcriptional level. Preliminary analysis of the regulatory motifs for these components suggests that the corresponding genes are likely to be co-regulated either together or in smaller subgroups, indicating that transcriptionally regulated modules might exist within complexes

Nitrogen Deprivation-Induced Production of Volatile Organic Compounds in the Arachidonic-Acid-Accumulating Microalga Lobosphaera incisa Underpins Their Role as ROS Scavengers and Chemical Messengers

Funding Information: PK and AC acknowledged the Blaustein Postdoctoral Fellowship from the Blaustein Center for Scientific Cooperation (BGU). We are grateful to Noga Sikron Peres for her help with the GC-MS analysis. VT was the chair of Sonnenfeldt-Goldman Career Development in Desert Research. Funding. This work was supported by a grant from the Ministry of Science, Technology and Space, Israel (grant number 3-12422).Peer reviewedPublisher PD

Oil Pollution Affects the Central Metabolism of Keystone Vachellia (Acacia) Trees

Vachellia (formerly Acacia) trees are native to arid environments in Africa and the Arabian Peninsula, where they often support the local animal and plant communities acting as keystone species. The aim of this study was to examine whether oil pollution affected the central metabolism of the native keystone trees Vachellia tortilis (Forssk.) and V. raddiana (Savi), as either adults or seedlings. The study was conducted in the Evrona Nature Reserve, a desert ecosystem in southern Israel where two major oil spills occurred in 1975 and in 2014. Leaf samples were collected to analyze the central metabolite profiles from oil-polluted and unpolluted adult trees and from Vachellia seedlings growing in oil-polluted and unpolluted soils in an outdoor setup. We found that oil pollution had a stronger effect on one-year-old seedlings than on adult trees, reducing the levels of amino acids, sugars, and organic acids. While adult trees are mildly affected by oil pollution, the effects on young seedlings can cause a long-term reduction in the population of these keystone desert trees, ultimately threatening this entire ecosystem.The research was part of a postcontamination monitoring program in the Evrona Nature Reserve, funded by the Israel Nature and Parks Authority (INPA) and managed by the HaMaaragIsrael National Nature Assessment Program. We are grateful for the ongoing support to the ADSSC (Winters G.) by the Israel Ministry for Science and Technology (MOST). M.F. was the recipient of a postdoctoral fellowship from the Jacob Blaustein Center for Scientific Cooperation.info:eu-repo/semantics/publishedVersio

The Impact of Student Hotspotting on Patients & the Jefferson Health System

Introduction “Super-utilizers”, patients with five or more hospital admissions in the past year, account for half of all healthcare expenditures and present a significant financial burden to our healthcare system. In Pennsylvania “super-utilizers” result in $1.25 billion of healthcare spending and Philadelphia has the highest number of “super-utilizers” in the state. To address this crisis, Jefferson University serves as one of four new national hubs for student hotspotting. Teams of interprofessional health professions students along with faculty and staff advisors enroll “super-utilizers” and provide targeted interventions to address social determinants of health, reduce hospitalizations and improve patient outcomes. Methods To examine the impact of this program on patients, objective healthcare outcomes were obtained from EPIC. Costs were obtained from the hospital Care Coordination team and national average figures to examine the impact on the Jefferson health system. Data were collected from six months pre-, during, and post-intervention for the hotspotting intervention group and for a matched control group of non-program participants. Pre- and post-intervention analysis was performed using random effects Poisson regression. Results Pre- and post-intervention analysis found a 6% reduction in ED visits, 48% reduction in the number of outpatient visits, 18% reduction in total days in hospital, and 14% reduction in 30 day readmissions for the intervention vs. the control group. Average total costs of care decreased for both the experimental and control group with a 36% cost reduction per patient in the intervention group. Conclusion Participation in student hotspotting is a promising way to help address the needs of “super-utilizes”. Student hotspotting appears to have a positive impact on reducing the costs of care and improving health outcomes for high utilizer patients

A Comprehensive Assessment of Qualitative and Quantitative Prodromal Parkinsonian Features in Carriers of Gaucher Disease-Identifying Those at the Greatest Risk

Carriers of GBA1 gene variants have a significant risk of developing Parkinson's disease (PD). A cohort study of GBA carriers between 40-75 years of age was initiated to study the presence of prodromal PD features. Participants underwent non-invasive tests to assess different domains of PD. Ninety-eight unrelated GBA carriers were enrolled (43 males) at a median age (range) of 51 (40-74) years; 71 carried the N370S variant (c.1226A > G) and 25 had a positive family history of PD. The Montreal Cognitive Assessment (MoCA) was the most frequently abnormal (23.7%, 95% CI 15.7-33.4%), followed by the ultrasound hyperechogenicity (22%, 95% CI 14-32%), Unified Parkinson's Disease Rating Scale part III (UPDRS-III) (17.2%, 95% CI 10.2-26.4%), smell assessment (12.4%, 95% CI 6.6-20.6%) and abnormalities in sleep questionnaires (11%, 95% CI 5.7-19.4%). Significant correlations were found between tests from different domains. To define the risk for PD, we assessed the bottom 10th percentile of each prodromal test, defining this level as "abnormal". Then we calculated the percentage of "abnormal" tests for each subject; the median (range) was 4.55 (0-43.5%). Twenty-two subjects had more than 15% "abnormal" tests. The limitations of the study included ascertainment bias of individuals with GBA-related PD in relatives, some incomplete data due to technical issues, and a lack of well-characterized normal value ranges in some tests. We plan to enroll additional participants and conduct longitudinal follow-up assessments to build a model for identifying individuals at risk for PD and investigate interventions aiming to delay the onset or perhaps to prevent full-blown PD

SIRT6 Promotes Hepatic Beta-Oxidation via Activation of PPARα

The pro-longevity enzyme SIRT6 regulates various metabolic pathways. Gene expression analyses in SIRT6 heterozygotic mice identify significant decreases in PPARα signaling, known to regulate multiple metabolic pathways. SIRT6 binds PPARα and its response element within promoter regions and activates gene transcription. Sirt6+/− results in significantly reduced PPARα-induced β-oxidation and its metabolites and reduced alanine and lactate levels, while inducing pyruvate oxidation. Reciprocally, starved SIRT6 transgenic mice show increased pyruvate, acetylcarnitine, and glycerol levels and significantly induce β-oxidation genes in a PPARα-dependent manner. Furthermore, SIRT6 mediates PPARα inhibition of SREBP-dependent cholesterol and triglyceride synthesis. Mechanistically, SIRT6 binds PPARα coactivator NCOA2 and decreases liver NCOA2 K780 acetylation, which stimulates its activation of PPARα in a SIRT6-dependent manner. These coordinated SIRT6 activities lead to regulation of whole-body respiratory exchange ratio and liver fat content, revealing the interactions whereby SIRT6 synchronizes various metabolic pathways, and suggest a mechanism by which SIRT6 maintains healthy liver

MHC-IIB Filament Assembly and Cellular Localization Are Governed by the Rod Net Charge

Actin-dependent myosin II molecular motors form an integral part of the cell cytoskeleton. Myosin II molecules contain a long coiled-coil rod that mediates filament assembly required for myosin II to exert its full activity. The exact mechanisms orchestrating filament assembly are not fully understood., negatively-charged regions of the coiled-coil were found to play an important role by controlling the intracellular localization of native MHC-IIB. The entire positively-charged region is also important for intracellular localization of native MHC-IIB.A correct distribution of positive and negative charges along myosin II rod is a necessary component in proper filament assembly and intracellular localization of MHC-IIB