Biology subjects

Hoog, J.

Publications and source records attributed to Hoog, J..

4 recordsLinked to original sources

bioRxiv2019

Microscaled Proteogenomic Methods for Precision Oncology

Cancer proteogenomics integrates genomics, transcriptomics and mass spectrometry (MS)-based proteomics to gain insights into cancer biology and treatment efficacy. A proteogenomics approach was therefore developed for frozen core biopsies using tissue-sparing specimen processing with a \"microscaled\" proteomics workflow. For technical proof-of-principle, biopsies from ERBB2 positive breast cancers before and 48-72 hours after the first dose of neoadjuvant trastuzumab-based chemotherapy were analyzed. ERBB2 protein and phosphosite levels, as well as mTOR target phosphosites, were significantly more suppressed upon treatment in cases associated with pathological complete response, suggesting MS-based pharmacodynamics is achievable. Furthermore, integrated analyses indicated potential causes of treatment resistance including the absence of ERBB2 amplification (false-ERBB2 positive) and insufficient ERBB2 activity for therapeutic sensitivity despite ERBB2 amplification (pseudo-ERBB2 positive). Candidate resistance features in true-ERBB2+ cases, including androgen receptor signaling, mucin expression and an inactive immune microenvironment were observed. Thus, proteogenomic analysis of needle core biopsies is feasible and clinical utility should be investigated.

cancer biology↗

bioRxiv2019

Social value unblocks Pavlovian reinforcement learning in male rats

Many species, including humans, are sensitive to social signals and their valuation is important in social learning. When social cues indicate that another is experiencing reward, they could convey vicarious reward value and prompt social learning. Here, we introduce a task that investigates if vicarious reward delivery in male rats can drive reinforcement learning in a formal associative learning paradigm. Using the blocking/unblocking paradigm, we found that when actor rats have fully learned a stimulus-self reward association, adding a cue that predicted additional partner reward unblocked associative learning about this cue. In contrast, additional cues that did not predict partner reward remained blocked from acquiring associative value. Preventing social signal exchange between the partners resulted in cues signaling partner reward remaining blocked. Taken together, these results suggest that vicarious rewards can drive reinforcement learning in rats, and that the transmission of social cues is necessary for this learning to occur.

animal behavior and cognition↗

bioRxiv2018

Nuclear envelope budding is an evolutionary conserved phenomenon

Nuclear envelope budding (NEB) is a recently discovered alternative pathway for nucleocytoplasmic communication distinct from the movement of material through the nuclear pore complex. Through quantitative electron microscopy and tomography, we demonstrate how NEB is evolutionarily conserved from early protists to human cells. In the yeast Saccharomyces cerevisiae, NEB events occur with higher frequency during heat shock, upon exposure to arsenite or hydrogen peroxide, and when the proteasome is inhibited. Yeast cells treated with azetidine-2-carboxylic acid, a proline analogue that induces protein misfolding, display the most dramatic increase in NEB, suggesting a causal link to protein quality control. This link was further supported by both localization of ubiquitin and Hsp104 to protein aggregates and NEB events, and the evolution of these structures during heat shock. We hypothesize that NEB is part of normal cellular physiology in a vast range of species and that in S. cerevisiae NEB comprises a stress response aiding the transport of protein aggregates across the nuclear envelope. Significance StatementA defining feature of eukaryotes is the nuclear envelope, a double lipid bilayer that serves to isolate and protect the cells genetic material. Transport of large molecules over this barrier is believed to occur almost exclusively via the nuclear pores. However, herpes virions and mega ribonucleoproteins (megaRNPs) use an alternative means of transport - via nuclear envelope budding (NEB). Here, we show NEB is a ubiquitous eukaryotic phenomenon and increases when exposed to various forms of cellular stress. NEB frequency was maximal when the cell was challenged with a drug that induces protein misfolding, indicating this transport pathway plays a role in protein quality control. These results imply that NEB is an underappreciated yet potentiallyfundamental means of nuclear transport.

cell biology↗

bioRxiv2018

Gender balance in time-keeping at life science conferences

Scientific conferences are biased against women when selecting speakers, but recent studies showed a positive trend where the ratio of invited female speakers had increased. We have recorded speaking times at 11 different conferences during 2016-2017 to analyze which factors influenced a speakers time keeping. Men and women went over time 47% and 41% of the talks, respectively. In a regression analysis, it was found that the most important factors that influences how long a presenter spoke was 1) their allocated time, 2) their career stage and 3) the level of time keeping enforcement. It was also found that gender and the size of the conference contributed significantly towards the speakers timing. Male speakers exceeded their allocated time more frequently than female speakers, especially at large conferences (60% vs 49%). Since conferences are an important arena for science dissemination this might have a negative impact on female scientists careers.

scientific communication and education↗