1,189 research outputs found
Design and properties of a Myc derivative that efficiently homodimerizes
No full textbHLH and bHLHZip are highly conserved structural domains mediating DNA binding and specific protein-protein interactions. They are present in a family of transcription factors, acting as dimers, and their selective dimerization is utilized to switch on and off cell proliferation, differentiation or apoptosis. Myc is a bHLHZip protein involved in growth control and cancer, which operates in a network with the structurally related proteins Max, Mad and Mnt. It does not form homodimers, working as a heterodimer with Max; Max, instead, forms homodimers and heterodimers with Mad and Mnt. Myc/Max dimers activate gene transcription, while Mad/Max and Mnt/Max complexes are Myc/Max antagonists and act as repressors. Modifying the molecular recognition of dimers may provide a tool for interfering with Myc function and, in general, for directing the molecular switches operated via bHLH(Zip) proteins. By molecular modelling and mutagenesis, we analysed the contribution of single amino acids to the molecular recognition of Myc, creating bHLHZip domains with altered dimerization specificity. We report that Myc recognition specificity is encoded in a short region within the leucine zipper; mutation of four amino acids generates a protein, Omomyc, that homodimerizes efficiently and can still heterodimerize with wild type Myc and Max. Omomyc sequestered Myc in complexes with low DNA binding efficiency, preventing binding to Max and inhibiting Myc transcriptional activator function. Consistently with these results, Omomyc produced a proliferation arrest in NIH3T3 cells. These data demonstrate the feasibility of interfering with fundamental biological processes, such as proliferation, by modifying the dimerization selectivity of a bHLHZip protein; this may facilitate the design of peptides of potential pharmacological interest
CTD profiles from oceanographic expedition HH/14 with RV HELMER HANSSEN in the Fram Strait in 2014
No full textSeawater temperature and pressure profiles from station HH14/00 from expedition HH14 (2014) in the Fram Strait. CTD data during the HH14 cruise were measured at regular intervals using a Seabird 911 Plus CTD on the R/V Helmer Hanssen. These profiles were used to characterise the physical structure of the water column in the Fram Strait
RISC RNA Sequencing in the Dorsal Raphè Reveals microRNAs Regulatory Activities Associated With Behavioral and Functional Adaptations to Chronic Stress
No full textThe Dorsal Raphe (DR) is the primary source of serotonergic input in the brain and a center for the homeostatic maintenance of the serotonergic tone. Under repeated stimulation, it can undergo adaptive modifications that alter serotonergic neurotransmission, which can lead to behavioral dysfunction. Post-transcriptional regulation by microRNAs is implicated in these adaptations. However, a global microRNA/target network effect on the DR neuroplasticity has yet to be elucidated. Here we investigate the microRNAs/mRNAs regulatory activity in the mouse DR after a chronic stress experience. First, we assessed the behavioral consequences of repeated restraint stress exposure and the functional adaptations of the DR by measuring the change in acute stress-induced serotonin release. Then, through next generation RNA-Seq of Argonaute2-bound RNA (RISC-Seq) we identified microRNAs and their targets that are associated to the RISC complex of the DR in unstressed and stressed mice. We mapped the potential microRNA/mRNA network within the stress-altered transcripts, uncovering new interactions that contribute to the chronic stress-induced DR modifications
Manierre family
No full textManierre family. L-R: Gina (Virginia) Helmer Manierre, George Manierre V (GV), George Manierre, Molly Manierre, Nora Manierre (later Scherzinger
Group of Merritt High School students at track meet
No full textL - R: Margaret Whitiaker, M. Corbett, Ronald Helmer, Mae Corkle, Donald Kirk, Cathy Aitken, Winston McLuhan and Della Clemens
Merritt High School student council, 1940-1941
No full textStanding L - R: Helmer Josephson, James Kelly, Yee Toy. Seated: Dick Goodall, Gilbert Josephson, Ralph Blumenauer, Jean Beveridge
Picnic at peach orchard
No full textImage of a group photograph taken at summer picnic at Peach Orchard. Identified are: back row L-R: Mr. Kirk, Mr. and Mrs. Dunrobin, Mr. Cooper, Mr. Helmer, Miss Cooper, Mr. Hespeler, Mrs. Agur Sr., Mrs Jim Sutherland, Mr. Clonston, Mr. Jim Sutherland, Miss Doris Cordy, Dr. Mathewson. Front row, named but not identified: Janet Sutherland, Mabel Cordy, Ruth Blair, Mrs. Mathewson, Marion Cartwright, Miss Emerson, Allanah Sutherland, Sheila Sutherland, Mrs. Helmer
Climate adaptation limits and the right to food security
No full textAvoiding severe impacts from anthropogenic climate change requires not only substantial reductions in greenhouse gas emissions but also further implementation of adaptation measures. In many regions with smallholder farming systems adaptation can help ensure food security despite significantly changing climatic conditions. However, the space for adaptation measures has limits. In this paper, we investigate hard and soft adaptation limits and discuss their relevance to food security in smallholder farming food systems. We argue that soft adaptation limits can be defined by sufficiency levels of justice like basic needs, capabilities, human rights or levels of well-being. Depending on social, cultural, political and economic conditions different communities realize different sufficiency levels of justice. Furthermore, as normative claims of justice, these sufficiency levels not only allow the social, cultural and political and economic conditions of social systems to be described but also define entitlements. We show that for smallholder farming systems with low social and economic standards these entitlements might mean that soft adaptation limits can define entitlements to social and economic improvements despite transformational adaptation to changing climatic conditions
Dissemination of knowledge from Cochrane systematic reviews in public health: Cross-sectional study: Stefanie Maria Helmer
No full textBACKGROUND: Appropriate dissemination of public health evidence is of high importance to ensure that relevant knowledge reaches potential stakeholders and relevant population groups. A wide distrust towards science and its findings indicates that communication thereof remains below its potential. Cochrane Public Health (CPH) provides an important source of high-quality scientific evidence. This study aimed to identify (1) dissemination strategies and (2) possible stakeholders of Cochrane Public Health reviews. METHODS: This is a cross-sectional, meta-research study. All 68 records (reviews or protocols) listed on the CPH website https://ph.cochrane.org/cph-reviews-and-topics up to 08.03.2022 were included. Record characteristics, dissemination strategy information and potential stakeholder details were coded by one author and 10% of records were checked by another author. Data were descriptively analysed. RESULTS: 53 reviews (46 systematic reviews, 6 rapid reviews, 1 scoping review) and 15 review protocols were included. The 53 reviews were published between 2010-2022 and included 1-153 primary studies. All reviews had an open-access plain language summary (PLS) in English with translations in 3-13 other languages. Although 16 of 53 reviews and 4 of 15 protocols reported any involvement in the review process of an advisory group, only 3 of 68 records included a dissemination plan aiming to inform non-academic audiences or policy. CONCLUSIONS: All identified records can be considered as relevant to a wide range of stakeholders and population groups. However, CPH reviews or protocols rarely report their dissemination strategies. It is unclear what dissemination strategies are used after CPH reviews are published. High relevance of CPH evidence for non-academic stakeholders and the general population highlights the need for adequate knowledge translation beyond academia. KEY MESSAGES: • Dissemination plans and implementation is rarely reported in CPH reviews. • Evidence from CPH reviews is relevant for a multitude of stakeholders
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